Angiotensin converting enzyme inhibitors in the treatment of hypertension (original) (raw)
Related papers
Journal of Pharmacology and Experimental Therapeutics, 2002
We have synthesized a prodrug of the angiotensin-converting enzyme (ACE) inhibitor captopril by coupling this drug covalently to the low molecular weight protein (LMWP) lysozyme. Such drug-LMWP conjugates can be used for renal drug delivery, since LMWPs accumulate specifically in the proximal tubular cells of the kidney. In the present study, we compared the effects of captopril-lysozyme and free captopril in male Wistar rats. ACE activity in plasma and the kidney was measured after intravenous bolus injection of either the captoprillysozyme conjugate (33 mg ⅐ kg Ϫ1 , corresponding to 0.2 mg ⅐ kg Ϫ1 captopril) or equivalent dosages of free captopril and lysozyme. The administration of the captopril-lysozyme conjugate resulted in less plasma ACE inhibition and a longer-lasting renal ACE inhibition compared with the free drug. Effects on
Acta pharmacologica et toxicologica, 1981
Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) orally, dose 0.2 mg/ml in drinking water. The treatment was initiated early and later during the course of developing hypertension. Continuously treated rats did not develop hypertension. Rats receiving captopril for 12 weeks remained normotensive, whereas withdrawal of the drug resulted in hypertension. Captopril treatment was effective in the rats with established hypertension and decreased the blood pressures to nearly normal values. Serum angiotensin converting enzyme (ACE) activity rose 3-fold in captopril treated rats. ACE in lung plasma membranes increased during captopril treatment, indicating that captopril induced biosynthesis of pulmonary ACE. No qualitative differences were found in the ACE from treated and not treated animals. The dissociation of the antihypertensive effect of captopril and of increased ACE activity ...
Captopril: pharmacokinetics, antihypertensive and biological effects in hypertensive patients
British Journal of Clinical Pharmacology, 1984
The kinetics of captopril plasma levels and of the drug-induced plasma converting enzyme activity (PCEA), plasma renin activity (PRA) and diastolic blood pressure (DBP) modifications were studied over 24 h after oral administration of captopril, 1 mg/kg, to ten hypertensive patients. 2 Free unchanged captopril pharmacokinetic parameters were: t1, _ 0.45 + 0.06 h; tmax:
Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme
British Medical Journal, 1979
and conclusions Captopril, a specific oral inhibitor of angiotensinconverting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may
Effect of Time and Dose on Angiotensin Converting Enzyme during Captopril Treatment in the Rat
Acta Pharmacologica et Toxicologica, 1983
The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (ACE) in serum, lungs and kidneys of the rat were studied. Normotensive Wistar rats were treated with a constant dose of captopril (0.2 mg/ml) during various time periods. In a second study rats were treated with different captopril doses (6.25 pg, 12.5 pg, 25 pg, 50 pg, and 200 pg/ml water) during three weeks. Serum ACE activity and pulmonary and kidney plasma membrane ACE concentrations were measured in both studies. Captopril treatment resulted in a rapid decrease of ACE in pulmonary and kidney plasma membranes and a simultaneously increase of serum ACE activity during the first day of treatment. This was followed by increased membrane concentrations of ACE in the lungs and return to normal ACE concentrations in membranes of kidneys, presumably due to increased ACE biosynthesis. Serum ACE activity continued to increase during the whole study. Serum ACE activity increased in a dose dependent manner during treatment with different captopril doses. Increased plasma membrane ACE concentrations were not observed in the rats treated with captopril at doses below 200 pg/ml water.
Hypertensive crisis treated with orally administered captopril
European Journal of Clinical Pharmacology, 1983
The value of the orally active converting enzyme inhibitor captopril in managing hypertensive crisis was tested in 9 untreated patients admitted to the emergency room, who were in need of rapid blood pressure reduction because of signs and symptoms of neurological and/or cardiac complications. During the 30 rain following administration of captopril 25mg the blood pressure decreased from 239/134 + 12/4 mmHg (mean + SEM) to 204/118 _+ 8/4mmHg (p<0.05). From that time on, captopril 200 to 300 rag/day was continued for 2 to 5 days. In 5 patients furosemide in a total dose of 40 to 160 mg i.v. or p. o. had also to be given in order to control the blood pressure. 12 and 24h after admission blood pressure averaged 140/93 and 139/86 mmHg respectively, in the patients treated with captopril alone, and 166/107 and 153/91 mmHg in those treated both with captopril and furosemide. The pronounced fall inblood pressure produced by blockade of the renin system was well tolerated and did not cause tachycardia. It appears, therefore, that captopril given alone or in association with a diuretic makes it possible to treat the hypertensive crisis without the need for monitoring in an intensive care unit.