Antihypertensive and renal effects of cilazapril and their reversal by angiotensin in renovascular hypertensive rats.
1. The antihypertensive and renal effects of cilazapril, a new angiotensin converting enzyme inhibitor, were evaluated in both two-kidney, one-clip Goldblatt hypertensive rats (n = 11) and normotensive rats (n = 6). 2. Intravenous infusion of cilazapril (1 mg/kg followed by 25 micrograms min-1 kg-1) caused significant reductions of blood pressure from 163 +/- 3 to 122 +/- 4 mmHg and from 157 +/- 2 to 113 +/- 3 mmHg in two separate groups of hypertensive rats and from 124 +/- 1 to 105 +/- 2 mmHg in normotensive rats. The hypotensive effect in terms of absolute value of percentage change was greater in hypertensive rats than in normotensive rats (41 +/- 6 vs 20 +/- 3 mmHg or 25 +/- 4% vs 16 +/- 2%, respectively). 3. Cilazapril increased glomerular filtration rate, urine flow, and absolute and fractional excretion rates of sodium and potassium in the non-clipped kidney of hypertensive rats. In contrast, the clipped kidney exhibited a depressed renal function during cilazapril infusion. 4. In normotensive rats, the hypotensive and enhanced renal function responses to cilazapril were much less than those of the non-clipped kidney of hypertensive rats. 5. Superimposed administration of either angiotensin II or angiotensin III during cilazapril infusion completely reversed the blood pressure and bilateral renal responses of cilazapril in both hypertensive and normotensive rats. 6. These results indicate that cilazapril reduces arterial pressure and enhances renal excretion mainly via inhibition of angiotensin II and angiotensin III formation.
Ding
Y A
YA
Department of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chang
S T
ST
Shieh
S M
SM
Huang
W C
WC
D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D017315:Cilazapril; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011724:Pyridazines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000809:Angiotensins; D011724:Pyridazines; D000804:Angiotensin II; D000805:Angiotensin III; D017315:Cilazapril