Clinical Effects of Calcium Antagonists in Hypertensive Diabetics

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SummaryThe incidence of hypertension and coronary artery disease among diabetic patients is approximately two to three times greater than in nondiabetics. Recent evidence suggests that even moderately elevated blood pressure levels may result in diabetic complications involving the eyes or kidneys. However, treatment of diabetic patients with antihypertensive drugs may have a deleterious metabolic effect. Previous studies have suggested that calcium antagonists may reduce insulin secretion and therefore impair glucose tolerance. This has not been substantiated clinically: in general, it would appear that calcium antagonists have a minimal hyperglycemic effect. To establish whether interruption of excitation-contraction coupling in arterial smooth muscle and altered stimulus-secretion coupling occur at pharmacologically equivalent doses of calcium antagonist, the effect of nicardipine on insulin output and vascular resistance was studied in the isolated perfused rat pancreas and in eight hypertensive patients with impaired glucose tolerance during oral glucose tolerance testing (OGTT). Baseline insulin output in vitro was 86 ± 22 ng/min at 8.0 mM glucose and 2.5 mM calcium. Application of 10 mM nicardipine reduced insulin output to 86% of baseline, whereas output was reduced to 16% by 1 μM nicardipine and to 6% by 10 mM nicardipine. Changes in duodenopancreatic outflow indicated maximal vasodilation of the pancreas at all three concentrations of nicardipine (10 nM-10 mM). In vivo nicardipine 30 mg t.i.d. for 2 weeks reduced systolic blood pressure from 168 ± 2 mm Hg to 136 it 4 mm Hg(p < 0.001)anddiastolicblood pressure from 96 ± 3 mm Hg to 78 ± 2 mm Hg (p < 0.001). Neither glucose tolerance nor insulin release during OGTT were impaired by nicardipine. The results of the present study suggest that the dose of nicardipine that blocks arterial excitation-contraction coupling does not affect insulin secretion.

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