The effects of Cicletanine, a new antihypertensive agent on insulin release in rat isolated pancreas by the perfusion technique

Treatment of hypertension has reduced the incidence of stroke, heart failure and renal failure. However, the incidence of coronary heart disease is not reduced to the same degree. Many of the drugs advocated as first-line drugs in the step-wise therapy have been shown to cause carbohydrate intolerance and it is an independent risk factor in the development of coronary heart disease. It is thus important to identify the antihypertensive drugs that may cause deterioration in glucose tolerance. Cicletanine, the first derivative of the furopyridines, is a new class of antihypertensive agents. It acts directly on vascular endothelium cells by increasing prostacyclin synthesis. It also decreases intracytosolic calcium levels in smooth muscles. The purpose of this study is to evaluate the effects of Cicletanine on insulin release in rat isolated pancreas by the perfusion technique adapted from Loubatieres and co-workers (1972). Doses used were based on therapeutic peak plasma concentration. Diazoxide was used as a positive control ie a known insulin suppressant. Cicletanine at 1/10 and equivalent therapeutic concentrations (0.5 microgram/mL and 5.0 micrograms/mL) did not suppress insulin release. However, at concentration exceeding 10X its therapeutic levels (50 micrograms/mL) it begins to suppress insulin release. In conclusion, Cicletanine did not inhibit insulin release at concentrations within the therapeutic range.