Influence of the angiotensin converting enzyme inhibitor cilazapril, the ??-blocker propranolol and their combination on haemodynamics in hypertension

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Abstract
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 One patient out of 18 was withdrawn in the cilazapril phase.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 .ltoreq. 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. It was concluded that the combination of an ACE inhibitor and a .beta.-blocker can be an effective and well tolerated antihypertensive regimen and should no longer be excluded from therapeutic consideration.

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