Tissue renin-angiotensin systems in the heart and vasculature: possible involvement in the cardiovascular actions of converting enzyme inhibitors.
The existence of independently functioning local renin-angiotensin systems in a number of tissues has been firmly established by biochemical and functional evidence and, most recently, by the demonstration of genetic messages for components of the renin-angiotensin systems, such as renin and angiotensinogen, in several organs. In this review, local renin-angiotensin systems in the heart and vascular walls are described and the contribution of a local inhibition of converting enzymes to the cardiovascular actions of converting enzyme inhibitors is discussed. Most of the studies cited support the hypothesis that an inhibition of cardiac converting enzyme may be involved in the beneficial hemodynamic and metabolic actions of converting enzyme inhibitors in cardiovascular disease, such as hypertension and congestive heart failure, independent of the circulating renin-angiotensin system. Local effects on cardiac converting enzyme may contribute to the ability of converting enzyme inhibitors to reduce cardiac hypertrophy. Similarly, local converting enzyme inhibition in the vascular wall may not only constitute a mechanism involved in the antihypertensive effects of converting enzyme inhibitors, but may also contribute to the regression of hypertension-induced vascular hypertrophy. In addition to reduced local angiotensin II generation, converting enzyme inhibition may engender a potentiation of the local effects of kinins. This mechanism may be more important to the cardiovascular actions of converting enzyme inhibitors than initially thought.
Unger
T
T
Department of Pharmacology, University of Heidelberg, Federal Republic of Germany.
Gohlke
P
P
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A