Chronic administration of resveratrol prevents biochemical cardiovascular changes in fructose-fed rats.

BACKGROUND: There seems to be a link between the cluster of risk factors known as insulin resistance syndrome with endothelial dysfunction. Resveratrol (3,4,5-trihydroxyestilbene) (RV), an antioxidant found in many components of the human diet, has been proposed as an effective agent in the prevention of several pathologic processes. This study examined the effect of chronic administration of RV on endothelial nitric oxide synthase (eNOS) activity in cardiovascular tissues and on plasma lipid peroxidation in fructose-fed rats (FFR), an experimental model of this syndrome. METHODS: Male Sprague Dawley rats were separated into four groups: Control, Control + RV, FFR, and FFR + RV (n = 8 in each group). The RV (10 mg/kg/d by gavage) and fructose (10% in drinking water) were administered for 45 days. Metabolic variables and systolic blood pressure (BP) were measured. The eNOS activity was estimated in the mesenteric arterial bed and cardiac tissue homogenates by conversion of (3)H-arginine to (3)H-citrulline. Lipid peroxidation was estimated through the measurement of plasmatic thiobarbituric acid-reactive substances (TBARS). RESULTS: The RV chronic treatment prevented the increase in systolic BP and cardiac hypertrophy, restored FFR mesenteric and cardiac eNOS activities, and decreased the elevated TBARS levels that characterize FFR, without an effect on other metabolic variables. CONCLUSIONS: In concert with other effects, the increase in eNOS activity may contribute to the protective properties attributed to RV and, thus, to its beneficial effects on the cardiovascular system. These results suggest that an adequate supplementation of RV might help to prevent or delay the occurrence of atherogenic cardiovascular diseases associated to insulin-resistant states.

Effects of barium and 5-hydroxydecanoate on the electrophysiologic response to acute regional ischemia and reperfusion in rat hearts.

The aim of this work was to investigate the role of the inward rectifying (K1) and the sarcolemmal ATP-sensitive K+ (K-ATP) channels in the electrical response to regional ischemia and the subsequent development of ventricular tachyarrhythmias on reflow (RA). Surface electrograms (ECG) and the transmembrane potential from subepicardial left ventricular cells were recorded in spontaneously beating rat hearts perfused with buffer alone (controls) or exposed to 100 microM BaCl2 or 100 microM 5-hydroxydecanoate (5-HD) to block either K1 or K-ATP channels respectively. After 20 min of equilibration and 10 min of control recordings, the left anterior descending coronary artery was occluded for 10 min. This was followed by reperfusion. The effects of regional ischemia as well as those of reperfusion (10 min) were recorded throughout. In the three groups, ischemia induced a modest decrease in heart rate and a sharp reduction in resting potential within 3 min. The latter as well as the accompanying depression of propagated electrical activity were enhanced by Ba2+. A partial recovery of the resting potential was observed in all groups during the last 2 min of coronary occlusion. Concomitantly, a slight reduction in the action potential duration was found in the control hearts. This effect was blocked by 5-HD. Under Barium the action potential duration increased by a factor of 3 and its ischemic variations were minimized. Severe sustained ventricular tachyarrhythmias developed on reflow in the controls and in the 5-HD exposed hearts. Barium limited the duration of arrhythmic episodes to a few seconds. Our data indicate that the initial electrical effects of ischemia are unrelated to activation of ATP sensitive K+ channels and that gK1 dominates the K+ membrane conductance at this stage. Furthermore, they show that action potential lengthening limits the duration of arrhythmic episodes triggered by reperfusion. This suggests that electrical heterogeneity plays an important role in the perpetuation of reperfusion arrhythmias.

4-Aminopyridine: effects on electrical activity during ischemia and reperfusion in perfused rat hearts.

We investigated the effects of 2 and 4 mM 4-aminopyridine (4-AP,--blocker of the transient outward current I(to) on the electrophysiological response to regional ischemia and reperfusion. Spontaneously beating rat hearts were subjected to coronary occlusion (10 min) followed by reperfusion. The surface electrogram and the membrane potential from subepicardial left ventricular cells were recorded throughout. The basal effect of 4-AP was a dose dependent increase in the action potential duration (APD90) without changes in the resting potential or the heart rate. During early ischemia resting depolarization (from 87.4 +/- 1.9-70.1 +/- 2.5 mV in the controls) was enhanced by 4 mM, 4-AP (84.3 +/- 1.4 mV vs. 61.7 +/- 1.3 mV) whereas APD90 increased by 73.5%. These effects resulted in a marked reduction in the duration of diastolic intervals that led to conduction failure and aborted responses. A partial recovery was found by the end of ischemia concomitant with APD90 shortening in both, control and 4-AP treated hearts. On reperfusion, 4-AP did not influence the initial incidence of ventricular tachyarrhythmias but decreased their duration from 531.5 +/- 56.3-260.7 +/- 100 sec (2 mM) and to 75.6 +/- 10.5 sec (4 mM). These data confirm others obtained by Henry et al. in isolated cells indicating that ischemia induces sequential changes in several K+ conductances. In addition, they show that changes in action potential characteristics may exert beneficial effects on reperfusion arrhythmias by acting on the arrhythmic substrate without suppressing the trigger mechanism.