Endothelium dependent vasomotor responses to endogenous agonists are potentiated following ACE inhibition by a bradykinin dependent mechanism.

OBJECTIVE

The aim was to investigate the effects of angiotensin converting enzyme inhibition on agonist induced endothelium dependent vasodilatation in vivo.

METHODS

Chronically instrumented conscious dogs (n = 8) were prepared for the measurement of coronary blood flow, diameter of the left circumflex coronary artery, mean arterial blood pressure, and heart rate. Intracoronary infusions of acetylcholine, adenosine, and bradykinin that induced dose dependent increases in coronary blood flow and diameter were performed with and without intracoronary administration of captopril (1 mg.kg-1) and enalapril (0.4 mg.kg-1). The effects were studied of concomitant inhibition of bradykinin actions by the specific B2 kinin antagonist HOE-140 (10(-7) M), NO-synthesis by NG-nitro-L-arginine-methyl ester (L-NAME, 2 x 10(-5) M), or cyclo-oxygenase by indomethacin (10(-7) M) (all intracoronary).

RESULTS

Neither captopril nor enalapril had significant vasodilating effect on the coronary vasculature when given alone. In contrast, both ACE inhibitors potentiated the agonist induced increases in coronary blood flow by bradykinin and acetylcholine (p < or = 0.01). HOE-140 strongly antagonised the effects of infused bradykinin and prevented the potentiation of acetylcholine responses by ACE inhibition. L-NAME caused hypertension and bradycardia and abolished the responses to acetylcholine and adenosine, but only partially attenuated the bradykinin induced increases in coronary blood flow. Simultaneous ACE inhibition reduced the hypertensive effect of L-NAME and partially restored the responses to bradykinin. Indomethacin reduced the responses to bradykinin but did not affect acetylcholine and adenosine induced coronary vasodilatation. The potentiation of the response to acetylcholine induced by ACE inhibition was, however, diminished by indomethacin.

CONCLUSIONS

In the coronary vasculature of the dog, ACE inhibitors enhance vasomotor responses to endothelium dependent agonists by facilitating the release of both NO and PGI2, a mechanism which is coupled to endogenously formed bradykinin. ACE inhibitors may thus mediate their effects in vivo partly by increasing the capacity of the endothelium to release autacoids.