Angiotensin-(1-7) increases osmotic water permeability in isolated toad skin

Angiotensin-(1-7) (Ang-(1-7)) increased osmotic water permeability in the isolated toad skin, a tissue with functional properties similar to those of the distal mammalian nephron. Concentrations of 0.1 to 10 μM were effective, with a peak at 20 min. This effect was similar in magnitude to that of frog skin angiotensin II (Ang II) and oxytocin but lower than that of human Ang II and arginine-vasotocin. The AT2 angiotensin receptor antagonist PD 123319 (1.0 μM) fully inhibited the response to 0.1 μM Ang-(1-7) but had no effect on the response to Ang II at the same concentration. The specific receptor antagonist of Ang-(1-7), A-779, was ineffective in blocking the response to Ang-(1-7) and to frog skin Ang II. The AT1 receptor subtype antagonist losartan, which blocked the response to frog skin Ang II, was ineffective in blocking the response to Ang-(1-7). The present results support the view of an antidiuretic action of Ang-(1-7) in the mammalian nephron.Fil: Santos, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Peral, Maria de Los Angeles. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coviello, Alfredo. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Prosopis alba seed flour improves vascular function in a rabbit model of high fat diet-induced metabolic syndrome

Aims: Prosopis alba flour is a natural source of nutrient and phytochemicals with potential effects on cardiovascular risk factors. The aim of this work was to examine the effects of dietary supplementation with Prosopis alba seed flour (Pr-Feed) on a high fat diet (FD)-induced rabbit model of metabolic syndrome. Main methods: Rabbits were separated in four groups: fed regular diet (CD); CD supplemented with Pr-Feed; fed on 18 % FD; FD supplemented with Pr-Feed. All diets were administrated for 6 weeks. After the feeding period body weights, mean blood pressure, heart rate and visceral abdominal fat (VAF) were determined; glucose tolerance test (GTT) was performed; total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), fasting glucose (FG), aspartate amino transferase, alanine amino transferase, bilirubin and creatinine were measured in serum. Abdominal aorta was excised and vascular function was assessed by acetylcholine relaxation and contractile response to KCl, norepinephrine and angiotensin II. Key findings: Phytochemical analyses showed that the main compounds of Pr-Feed were apigenin C-glycosides. FD increased VAF, FG, TG, reduced HDL-cholesterol and induced abnormal GTT. Pr-Feed addition to FD did not modify these alterations. Aortic rings from rabbits fed on FD exhibited an impaired relaxation-response to acetylcholine and increased agonist vasoconstrictor responses. Pr Feed-supplemented FD improved the response to acetylcholine, and prevented the increase of the contractile response to KCl, norepinephrine and angiotensin II. Significance: Results suggest that dietary supplementation with Pr-Feed, rich in apigenin C-glycosides, has vascular protector properties and could be used to prevent vascular alterations characterizing the metabolic syndrome.Fil: Cattaneo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Roco, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Alarcón, Gabriela del Jesús. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Isla, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; ArgentinaFil: Jerez, Susana Josefina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentin

Effect of angiotensin II and a2 receptor antagonists on angiotensin II-stimulated nitric oxide release

El objetivo del presente trabajo fue caracterizar la interacción entre el sistema adrenérgico y la liberación de óxido nítrico (ON) estimulada por angiotensina II en aorta de conejo. Anillos de aorta torácicase colocaron en un baño de órgano aislado. Se equilibró durante 30 min, se lavó y se agregó angiotensina II a diferentes dosis, dejándose actuar 20 min. En otro grupo se efectuaron dos estimulaciones con un intervalo de 60 min. Los antagonistas de angiotensina II: losartan, PD 123319 y Sar1-Leu8-angiotensina II; y el antagonista α2 adrenérgico (yohimbina), todos 10-5 M, y L-NAME o D-NAME 10-2 M, se agregaron antes de estimular con angiotensina II 10-6 M o 5.10-6 M. A otro grupo, además de losartan o PD 123319, se agregó yohimbina. La determinación de nitritos se realizó con el reactivo de Griess. La angiotensina II 10-8 M hasta 10-6 M, incrementó la producción de metabolitos de ON medidos como nitritos con respecto al control. A dosis mayores hubo una disminución con respecto a 10-6 M. La liberación de nitritos inducida por angiotensina II cayó en la segunda estimulación con la hormona en todos los casos, mientras el L-NAME la bloqueó. Los antagonistas de angiotensina II la incrementaron sólo a dosis máxima de la hormona, efecto anulado por yohimbina. Asimismo, yohimbina disminuyó la producción de nitritos a dosis de angiotensina II 5.10-6 M pero no 10-6 M. Estos resultados permiten postular que la liberación de ON inducida por angiotensina II sería en parte mediada por estimulación de receptores α2. Los antagonistas de angiotensina II desenmascararían este efecto a dosis máxima de la hormona, mientras que a dosis supramáximas prevalecerían mecanismos inhibitorios que serían compensados por activación α2.The aim of the present work was to characterize the interaction between the adrenergic system and angiotensin II-stimulated nitric oxide (NO) release in rabbit aorta. Rings of thoracic aorta were placed in an isolated organ bath. Equilibration was performed during 30 min, and after washing, angiotensin II was added at different concentrations, during 20 min. In another group two stimulations were performed with an interval of 60 min. Angiotensin II antagonists: losartan, PD 123319 and Sar1 -Leu8-angiotensin II, α2 adrenergic antagonist: yohimbine, all at 10-5 M and L-NAME or DNAME 10-2 M, were added before stimulation with angiotensin II 10-6 M or 5.10-6 M. In another group, besides losartan or PD 123319, yohimbine was added. Nitrite determination was performed with Griess reagent. Angiotensin II 10-8 to 10-6 M increased NO metabolite production measured as nitrites referred to the control. In higher concentrations there was a diminution in relation to 10-6 M. Angiotensin II nitrite release fell in the second stimulation with the hormone in all cases, whereas it was blocked by L-NAME. It was increased by angiotensin II antagonist only at maximal concentrations of the hormone, an effect abolished by yohimbine. Likewise, yohimbine diminished nitrite production at concentrations of angiotensin II of 5.10-6 but not at 10-6 M. These results allow us to postulate that NO release induced by angiotensin II would be in part mediated by α2 receptors. Angiotensin II antagonists unmask these effects at maximal concentrations of the hormone, whereas at supramaximal concentrations inhibitory mechanisms would prevail, which would be balanced by α2 activation.Fil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coviello, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Oral administration of zuccagnia punctata extract improves lipid profile, reduces oxidative stress and prevents vascular dysfunction in hypercholesterolemic rabbits

Background: The consumption of flavonoids has been shown to prevent cardiovascular diseases including atherosclerosis. In this sense, in a recent in vitro study we demonstrated that a rich in flavonoids extract from Zuccagnia punctata has beneficial effects on vascular function in aorta from hypercholesterolemic rabbits. Purpose: The aim of this study was to evaluate the ability of a hydroalcoholic extract from Z.puncata (ZpE) to prevent alterations induced by high cholesterol diet in rabbits. Methods: The major components of the ZpE, flavonoids, were analyzed by using a validated reversed phase HPLC method. Rabbits were separated in five groups: fed standard chow (CD); CD orally administrated 2.5 mg, 5 mg or 10 mg GAE/day ZpE (ZpE- CD); fed 1% cholesterol-enriched chow (HD); HD orally administrated 2.5 mg GAE/day ZpE (ZpE-HD); HD orally administrated 2.5 mg rosuvastatin/day (Ro-HD). All diets were administrated by 6 weeks. Body weights (BW), mean blood pressure (MAP), heart rate (HR), visceral abdominal fat (VAF), organ weight (heart, kidney, liver) and vascular morphology were determined. Total cholesterol (TC), triglycerides (TG), fasting glucose (FG), aspartate amino transferase (AST), alanine amino transferase (ALT), bilirubin, creatinine, thiobarbituric acids reactive substances (TBARS) and glutathione reduced/oxidized index were measured in serum. Abdominal aorta was excised and vascular function was assessed by acetylcholine and sodium nitroprusiate relaxation and contractile response to norepinephrine and angiotensin II. Results: The major compounds of ZpE identified were chalcones: 2′,4′-dihydroxy-3′-methoxychalcone and 2′,4′-dihydroxychalcone. Oral treatment with ZpE reduced MAP, TC, TG, TBARS, aortic intima/media ratio and increased glutathione reduced/oxidized index in HD rabbits. No differences were found in AST, ALT, bilirubin or creatinine. Acetylcholine relaxation was normalized and contractile response to norepinephrine and angiotensin II was reduced in ZpE-HD. Conclusion: Oral administration of ZpE as natural product in the prevention of cardiovascular disease related with hypercholesterolemia and endothelial dysfunction is very promising.Fil: Roco, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Alarcón, Gabriela del Jesús. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Medina, Mirta. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Zampini, Iris Catiana. Universidad Nacional de Tucuman. Instituto de Bioprospeccion y Fisiologia Vegetal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Bioprospeccion y Fisiologia Vegetal.; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Isla, Maria Ines. Universidad Nacional de Tucuman. Instituto de Bioprospeccion y Fisiologia Vegetal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Bioprospeccion y Fisiologia Vegetal.; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

Beneficial effects of hydro-alcoholic extract of Zuccagnia punctata against atherosclerosis in normal weight obesity accompanied by hypercholesterolemia rabbit model

Insulin resistance (IR) increases the synthesis of cholesterol so hypercholesterolemia is one regular feature of obesity. Rich in flavonoids Zuccagnia punctata extract (Zp-E) is a traditional herbal medicine found to be beneficial against hypercholesterolemia-induced oxidative damage. This study aimed to evaluate the effects of Zp-E in a diet-induced rabbit model of IR accompanied by hypercholesterolemia. The major components of the Zp-E were analyzed by using a reversed-phase HPLC method. Male hybrid rabbits (cross between New Zealand and Californian certificated breeds) were separated into six groups: 1: fed on regular chow (SD), 2: fed on SD supplemented with 18% fat and 0.3% cholesterol (HC-HFD), 3, 4, 5: fed on HC-HFD and orally administered 2.5 mg, 5 mg or 10 mg GAE/day of Zp-E, respectively, 6: fed on HC-HFD and orally administered 2.5 mg ezetimibe/kg/day. All diets were administered for 6 weeks. The major compounds of Zp-E identified were chalcones: 2′,4′-dihydroxy-3′-methoxychalcone and 2′,4′-dihydroxychalcone. Zp-E only at 2.5 mg GAE/day reduced total cholesterol and did not modify fasting glucose, visceral abdominal fat, or IR at any of the doses tested. Zp-E normalized TBARS levels, sudanophilic area, and intima/media ratio at all the doses tested while significantly improving acetylcholine relaxation only at 5 mg GAE/day. Despite Zp-E's failure to prevent IR under hypercholesterolemic conditions, the extract showed protective effects on blood vessels by preventing the formation of atherosclerotic plaque through its strong antioxidant properties

Nitric oxide modulates angiotensin II-induced endothelial vasoconstrictor prostanoid release

This study investigated the modulation of angiotensin II-induced endothelial prostanoid release in rabbit aortic rings. Two cumulative dose response curves with 90-min washing interval were performed. Incubation with l-NG-nitroarginine methyl ester (l-NAME) 10- 4 M increased angiotensin II maximal contractile response (Emax). This effect was reversed by indomethacin 10- 5 M, diphenyliodinum 10- 5 M, Tempol 10- 5 M or ascorbic acid 10- 4 M in both cumulative dose response curves and by SQ 29548 10- 6 M in the second cumulative dose response curve. When segments were treated with tetraethylamonium 10- 3 M but not with glibenclamide 10- 5 M during the washing period, l-NAME recovered its ability to enhance the E max in arteries incubated with SQ 29548. Conclusions: nitric oxide modulates angiotensin II-induced endothelial release of cyclooxygenase-dependent eicosanoids, one of which acts through thromboxane A2/prostaglandin H2 receptors and would decrease KCa channel activity. An increase in free radical production may account for the enhancement of such prostanoid release. Furthermore, it was found that in the present conditions, the release of the hyperpolarizing factor would improve in order to maintain the vascular tone.Fil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coviello, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Cross Talk between Angiotensin II and Alpha 1 Adrenergic Receptors in Rabbit Aorta: Role of Endothelium

Interaction between the renin-angiotensin system and the sympathetic nervous system has been proposed to be like a physiological regulation mechanism. The present work was designed to study the cross talk between angiotensin II and adrenergic receptors on the smooth muscle contractile response and the endothelium influence in this phenomenon. Homologous and endothelium independent desensitization of angiotensin II-contractile response was observed. Treatment with noradrenaline between two cumulative doses response curves (CDRC) to angiotensin II caused a rightward shift of the second CDRC in unrubbed arteries and increased the maximal response in rubbed arteries. Prazosin blocked these effects. No homologous desensitization of noradrenaline contractile response was found. Treatment with angiotensin II between two CDRC to noradrenaline caused a loss of affinity in the second CDRC in unrubbed arteries. Losartan was able to avoid this phenomenon. Maximal response was enhanced both in arteries with and without endothelium treated or not with angiotensin II. Results demonstrate homologous and endothelium-independent desensitization of the contractile response to angiotensin II but not to noradrenaline. In addition, heterologous and endothelium-dependent desensitization induced by noradrenaline and angiotensin II on the contractile response to each other was found. Furthermore, results provided the first evidence that there is an endothelium-dependent cross talk between α1-adrenergic and angiotensin II receptors in smooth muscle of rabbit aorta.Fil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Coviello, Alfredo. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Endothelium-dependent desensitization to angiotensin II in rabbit aorta: the mechanisms involved

The aim of this study was to characterize the role of the endothelium in angiotensin II-desensitization and its mechanisms of action. Rabbit aortic rings were exposed to increasing doses of angiotensin II (Ang II, 10–9 to 2.5 × 10–6) to generate two cumulative dose-response curves (CDRC I and II). A 50-min interval separated CDRC I and II. Desensitization was observed at all doses in unrubbed aortic tissue and at lower doses in rubbed aortic tissue. Tachyphylaxis was greater in arteries with endothelium. Treatment of intact rings with L-NG-nitroarginine methyl ester (L-NAME, 10–4 M) did not prevent this phenomenon. However, indomethacin (10–5 M) and miconazol (10–6 M) attenuated Ang II-desensitization. Treatment of unrubbed rings with nifedipine (10–6 M) and cromakalim (10–6 M) inhibited the effect of indomethacin. To confirm the involvement of K+ channels, unrubbed and rubbed aortic rings were treated with the KCa 2+ blockers apamin (10–7 M), tetraethylammonium (TEA, 10–3 M), and iberiotoxin (10–8 M), and the KATP blocker glibenclamide (10–5 M). In both arteries apamin, TEA, and glibenclamide abolished the tachyphylaxis without changes in the maximal response. Iberiotoxin diminished Ang II-desensitization in rubbed but not unrubbed arteries. Results from this study suggest that Ang II-desensitization involves endothelium-dependent and -independent mechanisms. Endothelium-dependent desensitization could be mediated by a cyclooxygenase-cytochrome P450 product, which could act by increasing KCa 2+ channel activity.La présente étude a eu pour but de caractériser le rôle de l’endothélium dans la désensibilisation induite par l’angiotensine II ainsi que les mécanismes qui seraient mis en cause. On a enregistré la tension isométrique produite par des anneaux aortiques de lapins. On a obtenu deux courbes dose-réponse cumulatives à intervalles de 50 min. On a observé une désensibilisation pour toutes les doses dans les aortes pourvues d’un endothélium et pour les doses plus faibles dans les aortes dépourvues d’endothélium. La tachyphylaxie a été plus forte dans les artères pourvues d’un endothélium. Le traitement des anneaux intacts au moyen de L-NAME (10–4 M) n’a pas prévenu ce phénomène. Toutefois, l’indométhacine (10–5 M) et le miconazol (10–6 M) ont atténué la désensibilisation induite par l’angiotensine II. Le traitement des anneaux pourvus d’un endothélium au moyen de nifédipine (10–6 M) et de cromakalim (10–6 M) a inhibé l’effet de l’indométhacine. Pour confirmer la participation des canaux K+, on a traité les anneaux aortiques pourvus et dépourvus d’endothélium avec les bloqueurs de KCa2+, apamine (10–7 M), tetraethylammonium (TEA, 10–3 M), ibériotoxine (10–8 M), et le bloqueur de KATP, glibenclamide (10–5 M). Dans les deux artères, l’apamine, le TEA et le glibenclamide ont supprimé la tachyphylaxie, sans modifier la réponse maximale. L’ibériotoxine a diminué la désensibilisation induite par l’angiotensine II dans les artères dépourvues d’endothélium mais pas dans les artères pourvues d’un endothélium. Ces résultats donnent à penser que la désensibilisation induite par l’angiotensine II a mis en cause des mécanismes dépendants et indépendants de l’endothélium et que les premiers seraient véhiculés par un produit cyclooxygénase-cytochrome P450 qui pourrait agir en augmentant l’activité des canaux KCa2+.Fil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coviello, Alfredo. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Role of nitric oxide on the vasorelaxant effect of atrial natriuretic peptide on rabbit aorta basal tone

The role of nitric oxide (NO) on the vasorelaxant effect of atrial natriuretic peptide (ANP) on the basal tone of rabbit aortic rings conditioned to angiotensin II (Ang II) was studied. ANP aortic relaxation and nitrite release were measured in the presence and absence of endothelium and a NO-synthase inhibitor. Ang II at 10 8 M triggered a contractile response, conditioning the vessel to a vasorelaxant effect of ANP (10 8 M). This effect was significantly enhanced by endothelium removal, NG-nitro-L-arginine methyl ester (L-NAME, 10 4 M), and methylene blue (10 5 M). ANP decrease of basal tone in Ang-II-sensitized aortic rings was improved when a higher concentration of Ang II was used (10 6 M). Basal and Ang-II-stimulated nitrite release were measured in stretched (S) and nonstretched (NS) aortic rings. Nitrite release was significantly increased in S rings (p < 0.001). L-NAME (10 4 M) partially inhibited nitrite release in both basal and Ang-II-stimulated S aortic rings. In NS aortic rings, the NO inhibitor did not inhibit basal nitrite release but blunted the Ang-II-stimulated nitrite level. A significant negative correlation between nitrite release and the ANP vasorelaxant effect on basal tone was dependent on the Ang-II-sensitizing dose. The present results demonstrate that ANP relaxant effects on aortic basal tone are related to NO levels, which are regulated by S- and Ang-II-concentration-dependent NO generation and quenching.Key words: atrial natriuretic peptide, nitric oxide, vascular reactivity, basal tone, rabbit aorta.On a examiné le rôle joué par le monoxyde d’azote (NO) dans l’effet vasorelaxant du peptide natriurétique auriculaire (ANP) sur le tonus basal d’anneaux aortiques de lapins sensibilisés à l’angiotensine II (Ang II). La relaxation aortique par l’ANP et la libération de nitrites ont été mesurées en présence et en absence d’endothélium et d’un inhibiteur de la NO synthase. L’Ang II (10–8 M) a déclenché une réponse contractile conditionnant le vaisseau à un effet vasorelaxant de l’ANP (10–8 M). Cet effet a été augmenté de manière significative par le retrait de l’endothélium ainsi que par NG-nitro-L-arginine méthyl ester (L-NAME, 10–4 M) et le bleu de méthylène (10–5 M). La diminution du tonus basal par l’ANP dans les anneaux aortiques sensibilisés à l’Ang II a été accrue lorsqu’une plus forte concentration d’Ang II a été utilisée (10–6 M). La libération de nitrites stimulée par l’Ang II et basale a été mesurée dans des anneaux aortiques étirés (É) et non étirés (NÉ). La libération de nitrites a été augmentée significativement dans les anneaux É (p < 0,001). L-NAME (10–4 M) a inhibé partiellement la libération basale ainsi que stimulée par l’Ang II dans ces anneaux. Dans les anneaux NÉ, l’inhibiteur de NO n’a pas inhibé la libération basale, mais il a diminué le taux de nitrites stimulés par l’Ang II. Une corrélation négative significative entre la libération de nitrites et l’effet vasorelaxant de l’ANP sur le tonus basal a été fonction de la dose sensibilisant à l’Ang II. Les résultats démontrent que l’effet relaxant de l’ANP sur le tonus basal aortique est lié aux taux de NO qui sont régulés par les muscles É ainsi qu’à la production et à l’inhibition de NO fonction de la concentration d’Ang II.Fil: Romano, Monica Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coviello, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Jerez, Susana Josefina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; Argentin

Hypercholesterolemia modifies angiotensin II desensitisation and cross talk between α1-adrenoceptor and angiotensin AT1 receptor in rabbit aorta

This study characterised the effect of a hypercholesterolemic diet on the interactions of hormone receptors in the rabbit aorta, both in homologous desensitisation to angiotensin II and cross talk between α1-adrenoceptors and angiotensin AT1 receptors. Rabbits were fed either a normal chow or a diet containing 1% cholesterol for 6-7-weeks. Isometric contractions were measured in endothelium-intact or endothelium-removed aortic rings from control and hypercholesterolemic rabbits. Concentration response curves to angiotensin II or noradrenaline incubated with or without prazosin or losartan were performed. In another group, the resting potential was recorded at baseline and following angiotensin II or noradrenaline stimulation. Rabbits fed a hypercholesterolemic diet showed higher plasma levels of total cholesterol and LDL-cholesterol and impaired relaxation to acetylcholine. Homologous desensitisation to angiotensin II was found in endothelium-intact but not in endothelium-removed arteries. Cross talk between α1-adrenoceptors and angiotensin AT1 receptors was modified with respect to physiological conditions. In control rabbits, angiotensin II desensitised the noradrenaline response but noradrenaline did not modify the angiotensin II-response. However, in hypercholesterolemic rabbits, angiotensin II sensitised the noradrenaline-response and noradrenaline desensitised the angiotensin II-response. Furthermore, the resting potential remains hyperpolarised after noradrenaline stimulation in hypercholesterolemic rabbits. Modifications in homologous desensitisation to angiotensin II and cross talk between α1-adrenoceptors and angiotensin AT1 receptors suggest that hypercholesterolemia induces early tissue dysfunction by altering endothelial and smooth muscle cell regulatory properties. This may be one of the mechanisms by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis.Fil: Jerez, Susana Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sierra, Liliana Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Scachi, Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Peral, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin