Effects of the new angiotensin-converting enzyme inhibitor imidapril on renal hemodynamics and function in anesthetized dogs.
The effects of a new angiotensin-converting enzyme (ACE) inhibitor, imidapril hydrochloride ((-)-(4S)-3-[(2S)-2- [[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino]propionyl]- 1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) and of its active metabolite, 6366 A (CAS 89371-44-8) on renal function were studied in anesthetized dogs and compared to the effects of enalapril and its active metabolite, enalaprilat. Intravenous (i.v.) administration of 6366 A at 30 micrograms/kg strongly inhibited angiotensin I-induced renal vasoconstrictive and pressor responses. 6366 A promptly lowered blood pressure and renal vascular resistance, and caused clear increases in renal blood flow and glomerular filtration rate. It also increased urine volume and urinary excretion of sodium and chloride. These renal effects were also produced by intraduodenal (i.d.) administration of 2 mg/kg of imidapril. However, the effects of i.d. imidapril began later, developed gradually and reached a plateau after 2 to 3 h. Enalaprilat (30 micrograms/kg i.v.) and enalapril (2 mg/kg i.d.) had renal effects similar to 6366 A and imidapril. In conclusion, the ACE inhibitor imidapril has beneficial effects on renal function via its active metabolite, and the effects appear to be essentially identical to those of enalapril.
Nishiyama
S
S
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Kanno
K
K
Yoneda
H
H
Yano
K
K
Yamaguchi
I
I
D000758:Anesthesia; D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D048289:Imidazolidines; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D012079:Renal Circulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D004656:Enalapril; D000803:Angiotensin I; C065166:imidapril; D015773:Enalaprilat