Kinin-related effects of angiotensin-converting enzyme inhibition

Clin Physiol Biochem. 1990;8 Suppl 1:6-15.

Abstract

Angiotensin-I-converting enzyme (ACE) converts angiotensin-I to angiotensin-II and splits bradykinin into inactive fragments. Inhibition of that enzyme attenuates kinin degradation and potentiates the action of kinins in many pharmacological investigations. Kinins are very potent vasodilating peptides which reduce blood pressure by lowering peripheral vascular resistance. Under experimental conditions in vitro kinins mediated a lot of metabolic and hemodynamic effects of the ACE inhibitors. However, it is still not known whether kinins also play a major role in the blood pressure-lowering effect of ACE inhibitors in vivo. New and highly specific assays are available to determine kinins in blood. But after ACE inhibition no homogeneous changes in circulating kinins are observed by reviewing recently published studies and even inhibition of kallikrein-kinin systems by either antibradykinin-antiserum or aprotinin does not clarify the role of kinins in the hemodynamic responses to ACE inhibition. The newly available bradykinin receptor antagonists inhibit in vitro and in vivo the effect of exogenous bradykinin. They were metabolized like kinins and in higher doses can develop kinin-like activities. After intravenous injection the bradykinin-receptor antagonists induce in vivo an increase in systemic blood pressure and thereby can reduce the blood pressure-lowering effect of ACE inhibitors markedly. However, it is unclear to date whether the bradykinin receptor antagonists developed their blood pressure-enhancing effect only by blocking the kinin-induced vasodilation or by some other stimulating effects on the vasopressor hormones. As long as the mechanisms of the hemodynamic action of the bradykinin antagonists are uncertain, no unequivocal interpretation of the results is possible and the role of kinins in the action of ACE inhibitors in vivo remains still uncertain.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Kallikrein-Kinin System / drug effects
  • Kallikrein-Kinin System / physiology
  • Kinins / physiology*
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Kinins