benazepril and Hypertension--Renovascular

The transport capacity of any membrane depends on its surface area and permeability. In addition, peritoneal capillaries are probably barriers to solute transport. Although no decisive use of antihypertensive drugs has been reported in continuous ambulatory peritoneal dialysis (CAPD) patients with hypertension, those drugs are known to have various effects on vessels. In the present study, we used a charge-coupled-device (CCD) camera in renovascular hypertensive dogs with mild renal insufficiency to investigate the effects of various antihypertensive drugs on the peritoneal capillaries. Renovascular hypertension was induced in the dogs by placing silver clips on both renal arteries to create 90% occlusion. After confirmation of elevation of blood pressure (usually 20 days after the operation), each dog's abdomen was opened while the animal was under general anesthesia. Using a CCD camera, the diameters of the small arteries of the peritoneum were measured after 3 days' oral administration of a placebo (n = 5); or of 8 mg CS866, a selective angiotensin II type 1 receptor blocker (n = 5); or of 10 mg benazepril, an angiotensin-converting enzyme inhibitor (n = 5); or of 10 mg amlodipine, a calcium antagonist (n = 5). In dogs receiving CS866, blood pressure decreased to 128 +/- 6 mmHg from 160 +/- 6 mmHg (p < 0.01). A similar decrease in blood pressure was observed with the use of the other drugs. The diameter of the small vessels increased by 28% +/- 6% in dogs receiving CS866 and by 24% +/- 5% in dogs receiving benazepril, as compared with 3% +/- 3% in dogs receiving the calcium antagonist. These data clearly demonstrate that blockade of the renin-angiotensin system produces an increase in solute clearance in hypertensive dogs with mild renal insufficiency and that such blockade may be applicable as therapy for hypertensive patients on CAPD.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aquaporins; Benzazepines; Blood Pressure; Calcium Channel Blockers; Dogs; Hypertension, Renovascular; Imidazoles; Microcirculation; Olmesartan Medoxomil; Peritoneum; Renal Insufficiency; Tetrazoles; Vasodilation

Converting enzyme inhibitors impair renal function of the kidney beyond a stenosis of the renal artery in humans and induce histological lesions in the clipped kidney of renal hypertensive rats. In two-kidney, one clip hypertensive rats, we compared the time course and magnitude of the biochemical effects of angiotensin converting enzyme inhibition on the plasma renin-angiotensin system, cardiac hypertrophy, renal lesions, and 24-hour blood pressure decrease induced by either intermittent angiotensin converting enzyme inhibition administration (benazepril PO, 10 mg/kg once a day, n = 93) or continuous administration (benazeprilat, 3 mg/kg per day via osmotic pumps, n = 92). Control rats (n = 91) received the drug vehicle intermittently or continuously. Mortality was significantly reduced by both intermittent (n = 3/93) and continuous (n = 3/92) inhibition compared with controls (n = 18/91) (P < .001). Changes in the plasma renin-angiotensin system and blood pressure were parallel. A continuous suppression of the activity of the plasma renin-angiotensin system was associated with a 24-hour decrease in blood pressure with continuous inhibition, whereas intermittent inhibition induced a similar fall in blood pressure only for the first hours after gavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Creatinine; Fibrosis; Heart Rate; Hypertension, Renovascular; Kidney; Male; Myocardium; Organ Size; Rats; Rats, Wistar; Renin; Urea

Single or repeated administration of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, (0.3-10 mg/kg p.o.) caused significant antihypertensive effects in renal and spontaneously hypertensive rats (SHR). The antihypertensive effects of benazepril hydrochloride was about 3 times as potent as that of captopril in these models. Single administration (0.3-3 mg/kg p.o.) of benazepril hydrochloride and enalapril maleate showed an equipotent antihypertensive effect in SHR. Benazepril hydrochloride (3-30 mg/kg p.o.), however, showed no clear effect on the blood pressure and heart rate in normotensive or DOCA/salt hypertensive rats.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Captopril; Desoxycorticosterone; Enalapril; Hypertension; Hypertension, Renovascular; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains