Angiotensin-converting enzyme inhibitors and the kallikrein-kinin system

Abstract

The role of plasma kinin in the hypotensive mechanism of angiotensin-converting enzyme (ACE) inhibitors in essential hypertensive patients and in a dog myocardiac ischemic model is discussed. Both an increase in plasma kinin and a decrease in plasma angiotensin II might contribute to the hypotensive effects of ACE inhibitors in a normal-renin group. In a low-renin group, the hypotensive mechanism of this drug may be mainly the increase in plasma kinin levels. The augmentation of urine volume and urinary sodium excretion may also be related to the hypotensive effects of ACE inhibitors, and this mechanism might be explained by the renal blood flow increase and augmented activity in the renal kallikrein-kinin system. In a dog myocardial ischemia model, when an apparent myocardial ischemia occurred in the constricted group, plasma kinin levels in coronary sinus blood increased significantly. Following infusion of kinin into the left main coronary artery, 0.1 ng/kg/min of kinin for 5 min did not cause any change in plasma kinin levels in the artery or coronary sinus. A dose of 10 ng/kg/min of kinin for 5 min produced a significant elevation in plasma kinin in the coronary sinus from 12.8 to 142 pg/ml without any change in plasma kinin in the artery. However, such a level of kinin had no significant effect on coronary circulation, myocardial metabolism, or ECG ST segment in either group. Thus, the role of increased kinin in this dog model still remains unclear. Further studies including the administration of ACE inhibitors or bradykinin antagonist will be necessary to reach conclusions about the role of kinin in the heart.