Effects of ACE inhibition with cilazapril on splanchnic and systemic haemodynamics in man.

Abstract

1 There is recent experimental evidence that the renin-angiotensin-system may play an essential role in producing splanchnic vasoconstriction. However, controversy exists as to the influence of ACE inhibition on splanchnic haemodynamics in man.We therefore investigated whether cilazapril, a structurally new and long-acting ACE inhibitor, interacts with angiotensin I-dependent changes in splanchnic haemodynamics in man, using an experimental model. 2 The effects of cilazapril on angiotensin I-induced splanchnic and systemic haemodynamics were studied in seven normotensive men using the hepatic venous catheter technique (indocyanine-green dye), right-heart catheterisation (thermodilution method),.intra-arterial blood pressure monitoring and systolic time-intervals. Dose-responses to angiotensin I were determined under ccrntrol conditions and 60 min after ACE inhibition with 5 mg oral cilazapril. Angiotensin I was infused intravenously at constant rates in an increasing dose-sequence until systolic blood pressure was greater than 30 mm Hg. 3 ACE inhibition with cilazapril did not change basal splanchnic or systemic haemodynamics to any relevant extent. The angiotensin I dependent increase in systemic and pulmonary resistance and pulmonary capillary wedge pressure was attenuated by cilazapril, as indicated by the shift of the dose-response curves to the right. In the splanchnic vascular bed angiotensin I dose-dependently increased splanchnic vascular resistance and also wedge hepatic venous pressure and decreased splanchnic blood flow. These angiotensin I induced haemodynamic changes were clearly suppressed by cilazapril. The angiotensin I dose needed to produce a 30% increase in splanchnic vascular resistance, given as mean and s.e.mean, was 1.7 ± 0.3 ,ug min-' during control-trials vs 7.3 ± 1.3 ,ug min-1 after ACE inhibition with cilazapril (P < 0.001). 4 We conclude that, in man, the influence of cilazapril on acute angiotensin I-mediated haemodynamic responses is present in the splanchnic vascular bed, and that the overall effects of cilazapril are consistent with both arterial and venous effects of the ACE inhibitor. Cilazapril effectively counteracts angiotensin I-induced splanchnic vasoconstriction.

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“…Nephrectomy [115], angiotensin-converting enzyme (ACE) [112,115] and specific angiotensin II receptor inhibition [116,117] prevent splanchnic vasoconstriction. Furthermore, direct infusion of angiotensin II in rats [118] and angiotensin I in humans causes splanchnic vasoconstriction, which is again reversed by ACE inhibition [119]. No clinical studies have been able to show a similar effect of ACE inhibitors on splanchnic perfusion.…”

Interference of angiotensin II and enalapril with hepatic blood flow regulation

“…The lack of an increase in absolute hepatic artery blood flow with enalapril despite decreased zero hepatic artery blood flow pressure and increasing hepatic arterial conductance may have been related to unchanged cardiac output and critically reduced perfusion pressure in our model. However, ACE inhibition in healthy volunteers, in patients after cardiac surgery, and in patients with congestive heart failure did not change the absolute splanchnic and hepatic blood flows (13,34,42).…”

Pharmacokinetics of Ibutilide in Patients with Heart Failure Due to Left Ventricular Systolic Dysfunction

“…In addition, in contrast to the previous studies performed with lidocaine, which were performed before the use of angiotensin converting-enzyme (ACE) inhibitors and ␤adrenergic receptor antagonists (␤-blockers) in patients with heart failure, at least 50% of the patients with heart failure enrolled in our study were medically managed with ACE inhibitors or angiotensin II receptor blockers, ␤-blockers, and/or diuretics. The ACE inhibitors have been shown to improve hepatic blood flow in patients with heart failure, 24,25 and ␤-blockers have been shown to improve hepatic blood flow in experimental models of heart failure. 26 Therefore, the hemodynamic stability and medical management in our patients with heart failure may explain the lack of alteration in pharmacokinetic characteristics of ibutilide in this study.…”