A calcium-channel blocker, amlodipine, attenuates insulin antinatriuresis but does not modulate insulin-mediated attenuation of cardiovascular reactivity in healthy man

Abstract

Background: Insulin exerts an antinatriuretic effect when administered acutely in vivo. Interestingly, insulin fails to reduce sodium excretion in rats receiving verapamil. The present study was undertaken in order to investigate whether the calcium-channel blocker amlodipine attenuates the antinatriuretic effect of insulin in humans.

Methods: Eight healthy lean men (32 +/- 2 years) were investigated on three different occasions; i.e. time-control, insulin infusion alone, and insulin infusion following pretreatment with amlodipine (5 mg x 1 during 10 days). During the experiments renal haemodynamics (insulin and PAH clearances) and segmental tubular sodium handling (sodium and lithium clearances) were investigated. The cardiovascular reactivity was also assessed by a graded noradrenaline infusion at the end of each experiment.

Results: Insulin infusion alone was accompanied by a significant 50% reduction in urinary sodium excretion. Following amlodipine pretreatment, euglycaemic insulin infusion was associated with an attenuated antinatriuretic response and the cumulative sodium excretion following 135 min of insulin infusion was significantly higher (24 +/- 4 vs 18 +/- 3 mmol; P < 0.05) as compared to insulin infusion alone. No significant differences in the proximal and distal tubular sodium handling respectively, were seen following CCB pretreatment. The results also show that the doses of noradrenaline required to increase the basal mean arterial blood pressure by 10 mmHg (262 +/- 38 vs 150 +/- 25 ng/kg/min; P < 0.05) and by 20 mmHg (431 +/- 36 vs 250 +/- 38 ng/kg/ min; P < 0.05) respectively, were significantly higher during the insulin infusion than during the time-control experiment. Pretreatment with amlodipine did not further modulate the cardiovascular reactivity.

Conclusion: Pretreatment with a calcium-channel blocker, amlodipine, attenuates the antinatriuretic effects of insulin leading to a significantly higher cumulative sodium excretion at the end of insulin infusion, which may be of clinical importance. Moreover, insulin attenuates the cardiovascular reactivity to a graded noradrenaline infusion, suggesting that insulin causes vasodilatation in healthy man.