Influence of the angiotensin converting enzyme inhibitor cilazapril, the beta-blocker propranolol and their combination on haemodynamics in hypertension.
This study compared the antihypertensive effects and the haemodynamic mechanisms of action of an angiotensin converting enzyme (ACE) inhibitor, a beta-blocker and the combination of both in patients with mild to severe hypertension. After a placebo run-in period of 2 weeks, patients were treated for 3 weeks with each of the following: cilazapril (2.5 mg daily) and propranolol (120 mg daily), in a randomized sequence, and thereafter a combination of the two drugs. Blood pressure, cardiac output (measured by Doppler ultrasound) and total peripheral resistance (TPR) in a sitting position at rest were determined. One patient out of 18 was withdrawn in the cilazapril phase. Both monotherapies yielded significant and similar reductions of diastolic blood pressure (average -10 mmHg). Cardiac output and TPR showed opposite effects. Cardiac output was lower with the beta-blocker than with the ACE inhibitor (3.4 versus 4.5 l.min-1), while TPR behaved conversely (2646 versus 2005 dyne.s.cm-5). The combination of both drugs lowered diastolic blood pressure significantly more than the monotherapies (average -20 mmHg); the haemodynamic effects of the monotherapies were attenuated by the combination (cardiac output = 3.7 l.min-1; TPR = 2170 dyne.s.cm-5). A sitting diastolic blood pressure of less than or equal to 90 mmHg could be achieved in six out of 17 patients with propranolol alone, in eight out of 18 with cilazapril alone, and in 14 out of 17 with the coadministration of both drugs. The combination was better tolerated subjectively than the beta-blocker alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Belz
G G
GG
Center for Cardiovascular Pharmacology, Wiesbaden, Federal Republic of Germany.
Breithaupt
K
K
Erb
K
K
Kleinbloesem
C H
CH
Wolf
G K
GK
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017315:Cilazapril; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D011433:Propranolol