Verapamil prevents insulin antinatriuresis in euglycemic rats.
To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II.
Gupta
A K
AK
Department of Medicine, University of Mississippi Medical Center, Jackson 39216.
Clark
R
R
Kirchner
K A
KA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012964:Sodium / Q000097:blood; D014700:Verapamil / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D007329:Insulin Antagonists; D002216:Captopril; D012964:Sodium; D014700:Verapamil