Dissociated effects of nicardipine on vascular tone and insulin secretion

Because Ca2+ antagonists may alter glucose homeostasis by blocking calcium entry into pancreatic beta-cells, this risk was evaluated for nicardipine, a new dihydropyridine derivative with vasodilatory effects. It was tested in vitro for its vascular and insulinotropic effects on isolated perfused rat pancreases. In vivo, an oral glucose tolerance test (OGTT) was conducted, and blood pressure was recorded in eight hypertensive patients with glucose intolerance who were given 90 mg/day nicardipine for 2 weeks in a single-blind placebo-controlled study. In vitro, insulin output was inhibited by 10(-4) M nicardipine but not by 10(-8) M and 10(-6) M, whereas significant changes in intrapancreatic perfusate flow indicated that vascular resistance was similarly reduced by all three concentrations. In vivo, blood pressure diminished significantly after nicardipine, but neither glucose tolerance nor insulin release was further impaired during OGTT. From these in vitro data and this short-term clinical follow-up, it is suggested that nicardipine reduces vascular tone at doses lower than those required to inhibit insulin secretion.