enalapril and cicletanine

In this multicentre controlled single blind trial the effectiveness and safety of cicletanine (100 mg/day) were compared with those of enalapril (20 mg/day) and of the combination of both drugs in the same doses in 72 patients (41 men, 31 women, mean age 64.1 +/- 8.3 years) with permanent moderate essential hypertension without severe cardiovascular complications. In the course of the trial, one patient in each of the three therapeutic groups was excluded either for insufficient effectiveness in monotherapy or for photosensitization under the combined treatment. After two months of treatment, the fall in blood pressure and the number of patients with normalized BP were similar in the groups treated with cicletanine or enalapril alone. In contrast, the cicletanine-enalapril combination produced a significantly greater fall of diastolic arterial pressure than cicletanine alone. In addition, there was a greater reduction of functional symptoms associated with arterial hypertension. Apart from the lone case of photosensitization observed with the combined treatment, only minor side-effects were encountered, including an episode of diarrhoea and a case of extrasystoles with the combination, and a case or nausea with lipothymia under cicletanine alone. There were no significant variations of biochemical values.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Diuretics; Drug Evaluation; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Pyridines; Randomized Controlled Trials as Topic

Angiotensin converting enzyme inhibitors (ACEI) are believed to protect remnant kidney, but all previous studies used the ligation model which causes severe hypertension, and very few have compared drugs in rats having similar control of blood pressure (BP). We compared rats with uremia obtained by 70% excision of total renal mass, a model which causes mild, late hypertension. Study I compared the effects of enalapril (E), cicletanine (C) and placebo (P) in uremic (U) rats fed a 0.50% (normal-high) Na diet. Study II compared the effects of E, C, P, and guanfacine (G) in U rats fed a diet restricted to 0.25% Na (normal-low). In study I, UP rats developed progressive hypertension (140, 146, 160 and 166 mm Hg at 3, 6, 9 and 12 weeks), proteinuria (240 mg/day at 9 and 12 weeks) which were not affected by E or C. The occurrence of end-stage renal disease (ESRD) led to the sacrifice of all rats after three months. All three groups had similar severe renal lesions (over 25% sclerosed glomeruli in 5 of 10 UP, 9 of 14 UE, 7 of 14 UC rats, with huge cystic tubular dilatations). In study II, rats could be sacrificed later (6 months) and had evidence of less severe renal disease. All the drugs tested prevented hypertension throughout the study (P less than 0.001), with lowest values in UE rats. E and G, but not C, reduced proteinuria. Renal damage was reduced with E and G, but not with C, despite similar BP in C and G rats. Thus, in contrast with what was obtained in the ligation model, ACEI affected neither the BP nor the renal lesions of rats made uremic by renal excision and fed a 0.50% Na diet. Moderate Na restriction improved the consequences of nephron loss and restored the anti-hypertensive effect of drugs. However, these drugs had a different effect on renal preservation: it was dramatic with E, good with G, and undetectable with C.

Topics: Animals; Antihypertensive Agents; Disease Models, Animal; Diuretics; Enalapril; Hypertension, Renal; Kidney; Male; Nephrectomy; Pyridines; Rats; Rats, Wistar; Sodium, Dietary; Uremia