Haemodynamic and hormonal effects of cilazapril in comparison with propranolol in healthy subjects and in hypertensive patients.
1. The purpose of the present studies was to compare the pharmacodynamic profile of the new ACE inhibitor cilazapril with the beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients. 2. Hormonal and haemodynamic responses at rest and after pharmacological interventions with angiotensin I and isoprenaline were investigated in six healthy volunteers following a 1 week treatment with placebo, propranolol (120 mg day-1) and cilazapril (2.5 mg day-1) in a double-blind cross over design with a wash-out period of 1 week between the different treatments. 3. Cilazapril induced a pronounced increase of plasma renin activity and angiotensin I concentrations, whereas after propranolol both parameters decreased. After both compounds slight decreases in angiotensin II concentrations were found. After the pharmacological challenges with angiotensin I and isoprenaline specific effects of the ACE inhibitor and beta-adrenoceptor blocker were found respectively. 4. Seventeen hypertensive patients received after a 2 week placebo period in random order cilazapril (2.5 mg day-1) or propranolol (120 mg day-1) for 3 weeks. A cross over design switched the patients to the other treatment. On the last day of each treatment period blood pressure, heart rate, cardiac output and total peripheral resistance were determined at rest and during handgrip test. In addition, bicycle exercise test was done and blood lactate concentrations were determined. 5. At rest blood pressure was lowered by both drugs, but total peripheral resistance increased after propranolol and decreased after cilazapril. After hand grip test, blood pressure was lowered after both drugs, but peripheral resistance decreased only after cilazapril.(ABSTRACT TRUNCATED AT 250 WORDS)
Kleinbloesem
C H
CH
Department of Pharma Clinical Research, Hoffmann-La Roche & Co. Ltd., Basle, Switzerland.
Erb
K
K
Essig
J
J
Breithaupt
K
K
Belz
G G
GG
D000328:Adult; D000368:Aged; D000803:Angiotensin I / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D017315:Cilazapril; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D006728:Hormones; D011724:Pyridazines; D017315:Cilazapril; D000803:Angiotensin I; D011433:Propranolol; D012083:Renin