Comparison of a new renin inhibitor and enalaprilat in renal hypertensive dogs.
The hypotensive efficacy of a potent new renin inhibitor (N alpha-isovaleryl-L-histidyl-L-prolyl-L-phenylalanyl-L-histidyl-ACHPA+ ++-L- phenylalanyl amide) containing (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy pentanoic acid (ACHPA) was compared with the converting enzyme inhibitor (enalaprilat) (MK-422) in conscious one-kidney dogs before and after tightening a renal artery clamp. Dose-response curves to 0.003 to 0.1 mg/kg/min i.v. infusions of the ACHPA-containing renin inhibitory peptide or enalaprilat (0.003-0.1 mg/kg i.v. bolus) were obtained in one-kidney dogs before and 3 days and 14 days after renal artery constriction. The ACHPA-containing renin inhibitory peptide and enalaprilat maximally decreased blood pressure by 10 +/- 2 and 9 +/- 2 mm Hg before constriction and by 12 +/- 2 and 12 +/- 4 mm Hg in dogs treated 14 days after renal artery constriction, respectively. Glomerular filtration rate and effective renal plasma flow were unaltered or slightly improved. In sharp contrast, both compounds elicited significant, dose-related decreases in blood pressure (-26 +/- 4 and -20 +/- 4 mm Hg, respectively), glomerular filtration rate (-21 +/- 3 and -23 +/- 3 ml/min), and renal plasma flow (-45 +/- 14 and -48 +/- 13 ml/min) in dogs examined 3 days after renal artery constriction. These data demonstrate that ACHPA-containing renin inhibitory peptide and enalaprilat are equally effective antihypertensive agents in dogs with renin-dependent renovascular hypertension and lend credence to the contention that the renin-angiotensin system supports renal function in hypertensive states in which renin levels are elevated.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004656:Enalapril / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015773:Enalaprilat; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D004656:Enalapril; D015773:Enalaprilat; D009842:Oligopeptides; D000092502:Renin Inhibitors; C051529:renin inhibitory peptide, 4-amino-5-cyclohexyl-3-hydroxypentanoic acid