Clofibrate improves myocardial ischemia-induced damage through regulation of renin-angiotensin system and favours a pro-vasodilator profile in left ventricle.

Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT1-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT2-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.

Captopril avoids hypertension, the increase in plasma angiotensin II but increases angiotensin 1-7 and angiotensin II-induced perfusion pressure in isolated kidney in SHR.

We investigated captopril effects, an ACE inhibitor, on hypertension development, on Ang II and Ang-(1-7) plasma concentrations, on Ang II-induced contraction in isolated kidneys, and on kidney AT1R from spontaneously hypertensive (SHR) rats. Five weeks-old SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30 mg/kg/day, in drinking water for 2 or 14 weeks. Systolic blood pressure (SBP) was measured, and isolated kidneys were tested for perfusion pressure and AT1R expression; while Ang II and Ang-(1-7) concentrations were determined in plasma. Captopril did not modify SBP in WKY rats and avoided its increase as SHR aged. Plasma Ang-II concentration was ∼4-5 folds higher in SHR rats, and captopril reduced it (P<0.05); while captopril increased Ang-(1-7) by ∼2 fold in all rat groups. Captopril increased Ang II-induced pressor response in kidneys of WKY and SHR rats, phenomenon not observed in kidneys stimulated with phenylephrine, a α1-adrenoceptor agonist. Captopril did not modify AT1R in kidney cortex and medulla among rat strains and ages. Data indicate that captopril increased Ang II-induced kidney perfusion pressure but not AT1R density in kidney of WKY and SHR rats, due to blockade of angiotensin II synthesis; however, ACE inhibitors may have other actions like activating signaling processes that could contribute to their diverse effects.

Effect of Citrus paradisi extract and juice on arterial pressure both in vitro and in vivo.

Citrus paradisi (grapefruit) consumption is considered as beneficial and it is popularly used for the treatment of a vast array of diseases, including hypertension. In the present study, the coronary vasodilator and hypotensive effects of Citrus paradisi peel extract were assessed in the Langendorff isolated and perfused heart model and in the heart and lung dog preparation. In both models, Citrus paradisi peel extract decreased coronary vascular resistance and mean arterial pressure when compared with control values (60 +/- 15 x 10(7) dyn s cm(-5) vs 100 +/- 10 x 10(7) dyn s cm(-5) and 90 mmHg vs 130 +/- 15 mmHg, respectively). These decreases in coronary vascular resistance and mean arterial pressure were blocked when isolated and perfused hearts and mongrel dogs were pre-treated with L-NAME. In humans, Citrus paradisi juice decreased diastolic arterial pressure and systolic arterial pressure both in normotensive and hypertensive subjects. Citrus paradisi juice produced a greater decrease in mean arterial pressure when compared with Citrus sinensis juice, cow milk and a vitamin C-supplemented beverage. However, more detailed studies are required to isolate, purify and evaluate the chemical compounds responsible for this pharmacological effect and to clarify its possible role for treating hypertension.

Coronary vasodilator activity of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora, and its possible mechanism.

The aim of this study was to investigate the biodynamic effects of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora flower petals and its possible mechanism on the Langendorff isolated and perfused heart model. Vulgarenol (5 microm) caused a statistically significant decrease in coronary vascular resistance (15.21 +/- 6.00 dyn s cm(-5) vs 36.80 +/- 5.01 dyn s cm(-5), control group), increased nitric oxide release (223.01 +/- 8.76 pmol/mL vs 61.00 +/- 12.00 pmol/mL, control group) and cyclic guanosine monophosphate accumulation in left ventricular tissue samples (142.17 +/- 8.41 pmol/mg of tissue vs 43.94 +/- 5.00 pmol/mg of tissue, control group). Pre-treatment with 3 microm gadolinium chloride hexahydrate, 100 microm N(omega)-nitro-L-arginine methyl ester hydrochloride, and 10 microm 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one significantly abolished the vulgarenol-induced coronary vascular resistance decrease, nitric oxide increased release and cGMP accumulation in left ventricular tissue samples. The results support the fact that nitric oxide and cyclic guanosine monophosphate are likely involved in the endothelium-dependent coronary vasodilation.

[Role of adenosine in the digitalis action on atrio-ventricular conduction in the dog heart]. / Participación de la adenosina en la acción digitalica sobre la conducción auriculo-ventricular del corazón canino.

In order to explore the hypothesis about the existence of an adenylic component on ouabain effects on the atrioventricular node, we perform experiments on anesthetized and vagotomized dogs. Decremental propagation of impulses through atrioventricular conduction system was evaluated stimulating the right atria at frequencies from 3.5 to 5.0 per second. Aminophylline antagonized and dipyridamole synergized the atrioventricular decremental conduction induced by digitalis. The blockade of purinergic receptors produced by aminophylline and the inhibition of adenosine endocytosis by dipyridamole could explain these antagonic and synergistic interaction with ouabain, and constitute an experimental evidence favorable to the possibility of the existence of a purinergic component on the digitalis mechanism of action.