Interference of angiotensin-converting enzyme inhibition with vasoactive peptides in the coronary circulation of dogs.
The coronary effects of angiotensin-converting enzyme (ACE) inhibitors and their mechanisms of action are not well understood. Because these drugs may interfere with hormone systems other than the reninangiotensin system (RAS), we studied modulation of the coronary effects of neurotensin, neuropeptide Y (NPY), and endothelin-1 (ET-1) by pretreatment with captopril in anesthetized, open-chest dogs. The left anterior descending coronary artery (LAD) was cannulated and perfused at a pressure equal to mean aortic blood pressure. Coronary blood flow (CBF) was measured by an electromagnetic flowmeter, subendocardial segment length by ultrasonic crystals. ACE inhibition (captopril 0.25 mg/kg), as an intracoronary (i.c.) injection, followed by an intracoronary infusion (0.25 mg/kg/h) did not affect the relative vasoconstrictor effects of ET-1 (10(-4)-10(-1) micrograms/kg i.c.) or neuropeptide Y (10(-3)-1 microgram/kg i.c.). However preinjection flow of a second dose-response curve of ET-1 was significantly higher in captopril-treated as compared with control animals. The increase in CBF induced by neurotensin (10(-3)-1 microgram/kg i.c.) was potentiated by captopril (40 +/- 14% after vs. 20 +/- 9% before captopril, p < 0.01, at the highest dose used). Changes in hemodynamics or in regional myocardial function could not explain altered effects of neurotensin. We therefore conclude that ACE inhibition does not interfere with the acute vasoconstrictor effects of ET-1 or NPY in this canine model but may reverse the long-term tonic coronary constrictor effect of ET-1. Potentiation of the neurotensin effect on CBF might be due to prevention of hydrolysis of neurotensin or to a cyclooxygenase-dependent mechanism.
Bauer
B
B
Medizinische Klinik, University of Würzburg, Germany.
Neubauer
S
S
Spindler
M
M
Dürr
R
R
Becker
H H
HH
Ertl
G
G
D000704:Analysis of Variance; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007261:Infusions, Intra-Arterial; D007269:Injections, Intra-Arterial; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D009496:Neurotensin / Q000008:administration & dosage / Q000494:pharmacology*; D012212:Rheology
D016232:Endothelins; D009478:Neuropeptide Y; D009496:Neurotensin; D002216:Captopril