Hypotensive and hemodynamic effects of the new non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline.
The hypotensive effects of N-[8-amino-1(S)-carboxyoctyl] -L-alanyl-L-proline (AB-47, CAS 120008-53-9) were examined in normotensive rats and various hypertensive rat models. The hemodynamic effect of AB-47 was also examined in anesthetized spontaneously hypertensive rats (SHR). In 2-kidney, 1-clip renal hypertensive rats (2K, 1C-RHR) and SHR, the single administration of AB-47 (10 mg/kg, p.o.) induced potent and long-lasting hypotensive effects. The repeated administration of AB-47 (1 to 10 mg/kg, p.o.) to SHR for 29 days produced a dose-dependently and sustained hypotensive effect of 20 to 70 mmHg. AB-47 (10 mg/kg, p.o.) had a weak hypotensive effect in DOCA-salt hypertensive rats but no effects in normotensive and 1-kidney, 1-clip renal hypertensive rats (1K, 1C-RHR). AB-47 (3 mg/kg, p.o.) reduced blood pressure in intact SHR but not in bilateral nephrectomized SHR. The single intravenous injection of AB-47 (10 to 100 micrograms/kg) dose-dependently lowered systemic blood pressure, left ventricular systolic pressure (LVSP) and dp/dtmax without affecting heart rate (HR) and these effects of AB-47 were more potent than those of captopril and enalaprilat. These results suggest that AB-47 is a potent and long-lasting hypotensive agent and may be useful for the therapy of both hypertension and congestive heart failure.
Shirota
M
M
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Iijima
M
M
Ushijima
T
T
Kajiwara
Y
Y
Kitabatake
K
K
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D003900:Desoxycorticosterone; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D006977:Hypertension, Renal / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides; C065126:N-(8-amino-1-carboxyoctyl)-alanyl-proline; D003900:Desoxycorticosterone; D004656:Enalapril; D002216:Captopril