Coronary vasodilation induced by angiotensin-converting enzyme inhibition in vivo: differential contribution of nitric oxide and bradykinin in conductance and resistance arteries.
BACKGROUND
We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation.
In seven anesthetized dogs, a Doppler guidewire was placed in the circumflex coronary artery to measure coronary flow velocity, and an ultrasound imaging catheter was introduced over the Doppler wire to measure coronary cross-sectional area. Drugs were infused directly into the left main coronary artery to minimize systemic effects. Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow. Pretreatment with N omega-nitro-L-arginine methyl ester (100 micromol/L intracoronary) to block nitric oxide synthase attenuated ramiprilat-induced increase in epicardial coronary cross-sectional area (P<.05) but not in coronary flow velocity or coronary blood flow. In contrast, pretreatment with the selective bradykinin antagonist HOE 140 (10 micromol/L) attenuated ramiprilat-induced increase in flow velocity (P<.025) and coronary blood flow (P<.05) but not epicardial coronary cross-sectional area. Pretreatment with indomethacin (5 mg/kg body wt IV) did not alter ramiprilat-induced increase in epicardial cross-sectional area, nor did it significantly influence coronary blood flow.


CONCLUSIONS
Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.
Sudhir
K
K
Cardiovascular Research Institute, University of California at San Francisco, USA.
Chou
T M
TM
Hutchison
S J
SJ
Chatterjee
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D015150:Echocardiography, Doppler; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; C065679:icatibant; D001120:Arginine; D019001:Nitric Oxide Synthase; D017257:Ramipril; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin