Mechanisms underlining gender differences in Phenylephrine contraction of normoglycaemic and short-term Streptozotocin-induced diabetic WKY rat aorta

The female gender reduces the risk, but succumbs more to cardiovascular disease. The hypothesis that shortterm 8 weeks) Streptozotocin-induced diabetes could produce greater female thanmale vascular tissue reactivity and themechanistic basiswere explored. Aortic ring responses to Phenylephrine were examined in age- and sex-matched normoglycaemic/diabetic rats. The normoglycaemic male tissue contracted significantly more than the normoglycaemic female and the male/female diabetic tissues. Endothelial-denudation, L-NAME or MB reversed these differences suggesting an EDNO-cGMP dependence. 17β-oestradiol exerted relaxant effect on all endothelium-denuded (and normoglycaemic endothelium-intact male) tissues, but not endotheliumintact normoglycaemic female. The greater male tissue contraction is attributable to absent 17β-oestradiolmodulated relaxation. Indomethacin blockade of COX attenuatedmale normoglycaemic and female diabetic tissue contraction (both reversed by L-NAME), but augmented diabetic male tissue contraction. These data are consistent with the raised contractile TXA2 and PGE2 in normoglycaemic male and diabetic female tissues, and the relaxant PGI2 in diabetic male (and female). The higher levels of PGI2 in the normoglycaemica and diabetic female perhaps explain their greater relaxant response to Acetylcholine compared to the respective male. In conclusion, there is an endothelium-dependent gender difference in the effect of short term diabetes on vascular tissue reactivity which is COX mediated

Effect of acidosis on the mechanism (s) of insulin-induced vasorelaxation in normal Wistar-Kyoto (WKY) rat aorta

The effect of acidosis on insulin-induced relaxation was studied in thoracic aortic rings (from Wistar–Kyoto (WKY) rats) with (+ED) or without (−ED) endothelium. The rings were mounted in normal (pH 7.4) or acidotic (pH 7.2) Krebs solution for isometric tension recording. Phenylephrine (PE, 3.0 µM)-contracted tissues were exposed to insulin in the presence or absence of various inhibitors. Insulin exerted similar concentrationdependent relaxation of +ED tissues in normal and acidotic pH. Endothelium denudation, significantly (pb 0.05) reduced insulin effect in normal, but not acidotic pH. Under normal pH, treatment with L-NAME or methylene blue significantly (pb 0.05) reduced insulin responses in the +ED (but not the −ED) tissues. The insulin effect was also significantly (pb 0.05) inhibited by tetraethylammonium (TEA; BKCa blocker), 4-Aminopyridine (4-AP; KV channel blocker), combined treatments (L-NAME+4-AP+TEA, in +ED tissues) or (4-AP+TEA, in −ED tissues). In either +ED or −ED tissues, indomethacin (cyclo-oxygenase inhibitor), glibenclamide (KATP channel blocker), barium chloride (Kir channel blocker) or Ouabain (a Na+ /K+ -ATPase inhibitor) had no effect. Except for methylene blue (effect on +ED tissues), none of the drug treatments inhibited insulin vasodilator effect in acidosis (+ED or −ED tissues). These data indicate that insulin exerts an endothelium-dependent and - independent vasodilatation in rat aorta which in normal pH is mediated via BKCa and Kv channels, including the EDNO-cGMP cascade. Acidosis abolishes the endothelium-dependent relaxation mechanism unraveling a novel mechanism that is as efficacious and is cGMP-, but not EDNO-, BKCa- or Kv-mediated

Effect of des-aspartate-angiotensin I on the actions of angiotensin II in the isolated renal and mesenteric vasculature of hypertensive and STZ-induced diabetic rats

10.1016/j.regpep.2005.02.007Regulatory Peptides1291-3213-21

Defferentiated gender ownership of cassava fields and implications for root yield variations in small holder agriculture of southeast Nigeria

Open Access JournalAs a result of their relatively limited access to production resources, it has been variously reported that women obtain lower yields from their individual crop fields than men. Cassava root yields obtained from farmers' fields in three villages of southeast Nigeria were compared using separate ownership of fields by gender as a factor. The result of the analysis fails to confirm lower yields from women's fields. Instead, mean fresh root yield was lower for fields owned individually by men than for those owned individually by women, and about the same for fields owned jointly by the whole family and those owned individually by women. This was apparently because of differences in the use of purchased inputs, especially hired labor and improved cassava varieties, and perhaps also due to differences in the age of cassava at harvest and the intercropping of cassava as a minor crop with yam

Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature

10.1016/j.peptides.2008.05.017Peptides29101773-178

Baicalein impairs vascular tone in normal rat aortas: role of superoxide anions

Acute exposure to the flavonoid baicalein inhibited endothelium-dependent relaxation in physiological arteries, although the mechanisms are not fully understood. We investigated the effect of baicalein on vascular tone in Wistar–Kyoto (WKY) rat isolated aortic rings in the presence and absence of oxidative stress to further determine the underlying mechanisms. Exposure to baicalein (10 μM) completely abolished endotheliumdependent relaxation induced by acetylcholine and attenuated significantly the endothelium-independent relaxation induced by sodium nitroprusside. Baicalein, similar to Nω-nitro-L-arginine methyl ester (L-NAME, 10 μM), potentiated significantly the contractile response of aortic rings to α1-adrenoceptor agonist phenylephrine. In the presence of L-NAME the baicalein effect on phenylphrine contraction or acetylcholine relaxation was unaltered, suggesting that these effects of baicalein are (like L-NAME effect) endothelial nitric oxide synthase (eNOS)/ endothelium-derived nitric oxide-dependent. Inhibition of cyclooxygenase activity with indomethacin (10 μM) or scavenging of superoxide anions with superoxide dismutase (150 units/ml), but not scavenging of hydrogen peroxide with catalase (800 units/ml), enhanced significantly by an essentially similar extent the relaxation to acetylcholine in baicalein-pretreated aortic rings. Relaxant effect to acetylcholine was significantly attenuated in control aortic rings, but was completely abolished in baicalein-pretreated aortic rings in the presence of reduced form of β- nicotinamide adenine di-nucleotide (β-NADH, 300 μM). Baicalein blocked β-NADH (300 μM)-induced transient contractions, suggesting that baicalein may have inhibited activity of NADH/NADPH-oxidase. Baicalein did not alter the failure of acetylcholine to induce relaxation in the presence of pyrogallol (300 μM). In summary, acute exposure to baicalein impairs eNOS/endothelium-derived nitric oxide-mediated vascular tone in rat aortas through the inhibition of endothelium-derived nitric oxide bioavailability coupled to reduced bioactivity of endothelium-derived nitric oxide and to cyclooxygenase-mediated release of superoxide anions

The aporphine alkaloid boldine improves endothelial function in spontaneously hypertensive rats

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of endothelial dysfunction in hypertension. In the present study, we investigated the effects of boldine on endothelial dysfunction in hypertension using spontaneously hypertensive rats (SHR), the most studied animal model of hypertension. SHR and their age-matched normotensive Wistar-Kyoto (WKY) rats were treated with boldine (20 mg/kg per day) or its vehicle, which served as control, for seven days. Control SHR displayed higher systolic blood pressure (SBP), reduced endothelium-dependent aortic relaxation to acetylcholine (ACh), marginally attenuated endothelium-independent aortic relaxation to sodium nitroprusside (SNP), increased aortic superoxide and peroxynitrite production, and enhanced p47phox protein expression as compared with control WKY rats. Boldine treatment significantly lowered SBP in SHR but not in WKY. Boldine treatment enhanced the maximal relaxation to ACh in SHR, but had no effect in WKY, whereas the sensitivity to ACh was increased in both SHR and WKY aortas. Boldine treatment enhanced sensitivity, but was without effect on maximal aortic relaxation responses, to SNP in both WKY and SHR aortas. In addition, boldine treatment lowered aortic superoxide and peroxynitrite production and downregulated p47phox protein expression in SHR aortas, but had no effect in the WKY control. These results show that boldine treatment exerts endothelial protective effects in hypertension, achieved, at least in part, through the inhibition of NADPH-mediated superoxide production

Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism

Increased oxidative stress is involved in the pathogenesis and progression of diabetes. Antioxidants are therapeutically beneficial for oxidative stress-associated diseases. Boldine (s-2,9-dihydroxy-1,10-dimethoxyaporphine) is a major alkaloid present in the leaves and bark of the boldo tree (Peumus boldus Molina), with known an antioxidant activity. This study examined the protective effects of boldine against high glucose-induced oxidative stress in rat aortic endothelial cells (RAEC) and its mechanisms of vasoprotection related to diabetic endothelial dysfunction. In RAEC exposed to high glucose (30 mM) for 48 h, pre-treatment with boldine reduced the elevated ROS and nitrotyrosine formation, and preserved nitric oxide (NO) production. Pre-incubation with β-NAPDH reduced the acetylcholine-induced endothelium-dependent relaxation; this attenuation was reversed by boldine. Compared with control, endothelium-dependent relaxation in the aortas of streptozotocin (STZ)-treated diabetic rats was significantly improved by both acute (1 μM, 30 min) and chronic (20 mg/kg/daily, i.p., 7 days) treatment with boldine. Intracellular superoxide and peroxynitrite formation measured by DHE fluorescence or chemiluminescence assay were higher in sections of aortic rings from diabetic rats compared with control. Chronic boldine treatment normalized ROS over-production in the diabetic group and this correlated with reduction of NAD(P)H oxidase subunits, NOX2 and p47phox. The present study shows that boldine reversed the increased ROS formation in high glucose-treated endothelial cells and restored endothelial function in STZ-induced diabetes by inhibiting oxidative stress and thus increasing NO bioavailability