Transgenic rat with overproduction of ubiquitous angiotensin-(1-7) presents neuroprotection in a model of ischemia and reperfusion

Recent studies showed that angiotensin-(1-7) has cerebroprotective actions in stroke. In the present study, we aim to test whether tissue overexpression of Angiotensin-(1-7), mainly in the brain provides neuroprotection in a model of ischemia/reperfusion by bilateral common carotid arteries occlusion/reperfusion (BCCAo/R). Evaluation of neurological deficit scores and bilateral asymmetry test (BAT) were performed seven days after transient BCCAo/R in transgenic rats (TG-7371) overexpressing Angiotensin-(1-7) and Sprague-Dawley (SD) rats. To assess blood-brain barrier (BBB) permeability Evans blue dye (EB) was intravenously injected. Cytokine levels were quantified in the whole brain through Elisa assay and oxidative stress was measured 7 days after ischemia. The expression of AT(1) and Mas receptors and inducible nitric oxide synthase (iNOS) was evaluated by RT-PCR. Neurological deficits were observed in both SD-BCCAo/R and TG-BCCAo/R, contrasting to sham-operated groups. However, TG-BCCAo/R showed a significant lower neurological score and latency in BAT when compared with SD-BCCAo/R. BBB integrity in TG-BCCAo/R was improved, since these animals showed lower extravasation of EB than SD-BCCAo/R. Interestingly, TG-BCCAo/R presented lower levels of pro-inflammatory cytokines when compared to SD-BCCAo/R. Levels of IL-10 were higher in SD-BCCAo/R than in SD control and even higher in TG-BCCAo/R. TG-BCCAo/R animals presented decreased levels of TBARS and increase in SOD activity and GSH levels when compared to SD sham rats. RT-PCR results showed higher levels of AT(1) receptor and iNOS in SD-BCCAo/R compared to TG-BCCAo/R, but no difference was observed for Mas receptor. The present study shows that lifetime increase in cerebral expression of an Ang-(1-7)-producing fusion protein induces neuroprotection in experimental global cerebral ischemia and reperfusion, reassuring that, pharmacological strategies leading to increase in Ang-(1-7) can be an additional tool for stroke therapy

Angiotensin-(1-7) potentiates the coronary vasodilatatory effect of bradykinin in the isolated rat heart

It has been shown that angiotensin-(1-7) (Ang-(1-7)) infusion potentiates the bradykinin (BK)-induced hypotensive response in conscious rats. The present study was conducted to identify Ang-(1-7)-BK interactions in the isolated rat heart perfused according to the Langendorff technique. Hearts were excised and perfused through the aortic stump under a constant flow with Krebs-Ringer solution and the changes in perfusion pressure and heart contractile force were recorded. Bolus injections of BK (2.5, 5, 10 and 20 ng) produced a dose-dependent hypotensive effect. Ang-(1-7) added to the perfusion solution (2 ng/ml) did not change the perfusion pressure or the contractile force but doubled the hypotensive effect of the lower doses of BK. The BK-potentiating Ang-(1-7) activity was blocked by pretreatment with indomethacin (5 mg/kg, ip) or L-NAME (30 mg/kg, ip). The Ang-(1-7) antagonist A-779 (50 ng/ml in Krebs-Ringer) completely blocked the effect of Ang-(1-7) on BK-induced vasodilation. These data suggest that the potentiation of the BK-induced vasodilation by Ang-(1-7) can be attributed to the release of nitric oxide and vasodilator prostaglandins through an Ang-(1-7) receptor-mediated mechanism

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17&#946;-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval

Numbaira: uma nova cultivar para o Brasil Central.

A cultivar de soja (Glycine max (L.) Merrill) Numbaira, que antes de seu lancamento foi identificada pela sigla Lo 75-1494, e proveniente do cruzamento Davis x IAC 71-1113, realizado em 1970/71, em Campinas, pela Secao de Leguminosas do Instituto Agronomico do Estado de Sao Paulo. Foi desenvolvido pelo metodo genealogico. IAC 71-1113 e uma linhagem F5, de florescimento tardio, selecionada a partir do cruzamento Hill x PI 240664. As selecoes foram feitas no Instituto Agronomico do Estado de Sao Paulo, em Campinas, ate a quarta geracao, sendo que a selecao final, correspondendo a uma progenie F5 (Lo 75-1494), foi realizada em Londrina, PR, no Instituto Agronomico do Parana, em 1974/75. A linhagem Lo 74-1494 foi testada inicialmente (1975/76) no Estado do Parana (Londrina e Guarapuava), pelo IAPAR, sendo posteriormente enviada pelo Centro Nacional de Pesquisa de Soja para testes no Brasil Central. Os testes foram realizados pelo Centro de Pesquisa Agropecuaria dos Cerrados (Distrito Federal e Mato Grosso), Empresa Goiana de Pesquisa Agropecuaria (Goias) e Empresa de Pesquisa Agropecuaria de Minas Gerais (Minas Gerais), nos anos de 1977/78 a 1979/80. A partir de 1978/79, foi testada tambem pela UNESP - Campus de Ilha Solteira. A Tabela I apresenta um resumo do comportamento medio de `Numbaira', comparativamente a UFV-1 e a IAC-. `Numbaira' apresenta flor roxa, pubescencia marrom, vagem marrom-clara, habito de crescimento determinado, semente amarela, com hilo preto. E resistente a pustula bacteriana (Xanthomonas ..

BRS Milena: cultivar de soja de ciclo medio de alta produtividade para o Cerrado.

A produtividade da soja no Cerrado torna a região competitiva nacional e internacionalmente. Entretanto, para atingir estabilidade produtiva e aprimorar o sistema de produção de grãos, torna-se necessária a obtenção de cultivares com resistência a doenças, como o cancro-da-haste, e com ciclo menor. Como resultado dos esforços da pesquisa, selecionou-se a cultivar BRS Milena. Os resultados, em todos os testes, mostram uma elevada produtividade e estabilidade em relação às cultivares usadas como testemunhas. O número de dias para maturação a classifica como uma cultivar de ciclo médio. Apresenta altura de plantas adequada à mecanização, e à ausência de acamamento nas condições em que tem sido testada. A 'BRS Milena' apresenta resistência às principais doenças da soja, tais como o cancro-da-haste, a mancha-olho-de-rã, o oídio e a pústula bacteriana.Made available in DSpace on 2011-04-09T17:11:12Z (GMT). No. of bitstreams: 1 pab98447.pdf: 166447 bytes, checksum: c423c46fcd347804454cf4fe9a015258 (MD5) Previous issue date: 2000-11-07200

Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats

Angiotensin-(1-7) [ANG-(1-7)] is a recently described heptapeptide product of the renin-angiotensin system. Because biosynthesis of ANG-(1-7) increases in animals treated with cardioprotective drugs and inactivation of the gene for angiotensin converting enzyme 2 [an enzyme involved in the biosynthesis of ANG-(1-7)] leads to the development of cardiac dysfunction, it has been suggested that ANG-(1-7) has cardioprotective properties. To directly test this possibility, we have generated transgenic rats that chronically overproduce ANG-(1-7) by using a novel fusion protein methodology. TGR(A1-7)3292 rats show testicular-specific expression of a cytomegalovirus promoter-driven transgene, resulting in a doubling of circulating ANG-(1-7) compared with nontransgenic control rats. Radiotelemetry hemodynamic measurements showed that transgenic rats presented a small but significant increase in daily and nocturnal heart rate and a slight but significant increase in daily and nocturnal cardiac contractility estimated by dP/d t measurements. Strikingly, TGR(A1-7)3292 rats were significantly more resistant than control animals to induction of cardiac hypertrophy by isoproterenol. In addition, transgenic rats showed a reduced duration of reperfusion arrhythmias and an improved postischemic function in isolated Langendorff heart preparations. These results support a cardioprotective role for circulating ANG-(1-7) and provide a novel tool for evaluating the functional role of ANG-(1-7)