Effects of a calcium entry blocker on blood pressure and renal function during angiotensin-induced hypertension.
The effects of the calcium entry blocker nitrendipine on blood pressure (BP) and renal hemodynamics were studied in rats with angiotensin II (ANG II)-induced hypertension. The ANG II was infused subcutaneously by implanted osmotic minipumps for 14 to 16 days. There was a progressive rise in BP in ANG II-infused rats to levels 58 mm Hg above basal by Day 10, whereas control rats with sham pumps remained normotensive. Nitrendipine or vehicle was administered by gavage to groups of control and hypertensive rats for 5 days, and clearance experiments were performed with the rats under anesthesia on the last day. The prolonged infusion of ANG II increased the renal vascular resistance and reduced the glomerular filtration rate and renal Na+ excretion. At a dose of 3 mg/100 g body weight, nitrendipine had no consistent effects on BP or renal function of control rats. By contrast, in rats with ANG II-induced hypertension, nitrendipine normalized both the BP and the changes in renal vascular resistance and glomerular filtration rate. Despite the fall in BP, nitrendipine caused a marked diuresis and natriuresis. Moreover, nitrendipine increased Na+ excretion of conscious, ANG II-hypertensive rats but not of controls. Thus, nitrendipine appears to be highly effective in reversing ANG II-induced hypertension and Na+ retention. These findings also indicate that the hypertension, renal vasoconstriction, and Na+ retention accompanying prolonged ANG II infusions may be mediated by calcium-dependent mechanisms.
Huelsemann
J L
JL
Sterzel
R B
RB
McKenzie
D E
DE
Wilcox
C S
CS
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D009568:Nitrendipine; D012964:Sodium; D009543:Nifedipine