Studies on the mechanism of the enhancement of the antihypertensive activity of captopril by a diuretic in spontaneously hypertensive rats.
Captopril (30 mg/kg/day orally for two days) in spontaneously hypertensive rats (SHR) inhibited serum angiotensin converting enzyme (ACE) activity 92.3%; increased plasma renin activity (PRA) 18-fold and reduced mean arterial blood pressure (MABP) 19 mm Hg. Hydrochlorothiazide (HCTZ) (100 mg/kg-day 1; 10 mg/kg-day 2, orally) increased PRA 3-fold but did not affect serum ACE or MABP. HCTZ plus captopril inhibited serum ACE 95.2%; increased PRA 38-fold and reduced MABP 47.5 mm Hg. Captopril or HCTZ plus captopril did not alter the responses of isolated aortic strips to norepinephrine (NE), serotonin, angiotensin II (AII) or isoproterenol. Pressor responses of conscious SHR to AII and NE were unaltered by captopril or HCTZ plus captopril although the bradykinin-induced depressor responses were significantly but equally potentiated. These results suggest that the potentiating effect of HCTZ is due to some mechanism that shifts the animal's blood pressure maintenance system to a renin-dependent state and is not due to changes in vascular reactivity.
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000008:administration & dosage; D014655:Vascular Resistance / Q000187:drug effects
D006852:Hydrochlorothiazide; D000804:Angiotensin II; D012701:Serotonin; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D009638:Norepinephrine