Nephrology Dialysis Transplantation, Vol 12, Issue 8 1600-1607, Copyright © 1997 by Oxford University Press
P Stenvinkel, A Ottosson-Seeberger, K de Potocki and A Alvestrand
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. Method: 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± 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/g/min; p <0.05) and by 20 mmHg (431±36 vs
350±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. Keywords:
cardiovascular reactivity; calcium-channel blocker; insulin; lithium
clearance; urinary disodium excretion
ORIGINAL ARTICLES
A calcium-channel blocker, amlodipine, attenuates insulin antinatriuresis but does not modulate insulin-mediated attenuation of cardiovascular reactivity in healthy man
Division of Renal Medicine , Department of Clinical Science, Huddinge University Hospital, Karolinska Instititue, Stockholm, Sweden; Corresponding author at: Department of Renal Medicine K56, Huddinge University Hospital, 141 86 Huddinge, Sweden
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