Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats.
1. The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radioactive microspheres technique. 2. Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 +/- 7 to 140 241 +/- 7 mm Hg (P less than 0.001), chronic treatment (1 x 10 mg kg-1 day-1 orally for 9 weeks) from 191 +/- 5 to 122 +/- 3 mm Hg P less than 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P less than 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P less than 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P less than 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3. With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P less than 0.001) and natriuresis (/124% and +111%, P less than 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4. It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fischli
W
W
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd, Basle, Switzerland.
Hefti
F
F
Clozel
J P
JP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D017315:Cilazapril; D004573:Electrolytes / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects; D008297:Male; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004573:Electrolytes; D011724:Pyridazines; D017315:Cilazapril