Isradipine and insulin sensitivity in hypertensive rats

The present study was designed to investigate the effect of a reduction in blood pressure, by using the calcium channel antagonist isradipine, on insulin sensitivity and vascular responses to insulin in conscious spontaneously hypertensive male rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique. Two groups of rats received isradipine at a dose of 0.05 or 0.15 mg. kg-1. h-1, whereas a third group received a continuous infusion of vehicle (15% DMSO). Both doses of isradipine were found to decrease mean blood pressure (-25 +/- 4 mmHg at the dose of 0.05 mg. kg-1. h-1 and -20 +/- 2 mmHg at the dose of 0.15 mg. kg-1. h-1) and to improve insulin sensitivity. Moreover, in the rats treated with the low dose of isradipine, we observed vasodilations in renal, superior mesenteric, and hindquarter vascular beds. In the untreated group, the euglycemic infusion of insulin (4 mU. kg-1. min-1) was found to cause vasoconstrictions in superior mesenteric and hindquarter vascular beds, but no changes in mean blood pressure, heart rate, or renal vascular conductance were found. In contrast, in the isradipine-treated groups, the same dose of insulin was found to produce vasodilations in the renal vascular bed and to abolish the vasoconstrictor responses previously observed. We concluded that short-term treatment with isradipine in SHR can lower blood pressure and improve insulin sensitivity, mainly through hemodynamic factors, as supported by experiments with hydralazine as a positive vasodilator control.