Endothelin-dependent effects limit flow-induced dilation of conductance coronary vessels after blockade of nitric oxide formation in conscious dogs

To determine whether endothelin (ET)-dependent effects limit shear stress-induced dilation of large epicardial coronary arteries after blockade of nitric oxide (NO) formation. In conscious dogs instrumented for measuring coronary blood flow (CBF) and external diameter (CD) of the circumflex coronary...

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Bibliographic Details
Published in:Cardiovascular research 2000-01, Vol.45 (2), p.470-477
Main Authors: PARENT, R, LAVALLEE, M
Format: Article
Language:English
Subjects:
Adenosine - pharmacology
Analysis of Variance
Animals
Biological and medical sciences
Coronary Circulation - drug effects
Coronary Vessels - drug effects
Dioxanes - pharmacology
Dogs
Endothelin Receptor Antagonists
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Hemodynamics. Rheology
NG-Nitroarginine Methyl Ester - pharmacology
Nitric Oxide Synthase - antagonists & inhibitors
Pyridines
Pyrimidines - pharmacology
Sulfonamides - pharmacology
Tetrazoles
Vasodilator Agents - pharmacology
Vertebrates: cardiovascular system
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Summary:To determine whether endothelin (ET)-dependent effects limit shear stress-induced dilation of large epicardial coronary arteries after blockade of nitric oxide (NO) formation. In conscious dogs instrumented for measuring coronary blood flow (CBF) and external diameter (CD) of the circumflex coronary artery, flow-dependent CD dilation was elicited by intracoronary (i.c.) adenosine (500 ng kg-1 min-1). I.c. adenosine increased CBF by 28 +/- 4 from 38 +/- 5 ml min-1 and CD by 0.25 +/- 0.03 from 3.53 +/- 0.07 mm without other hemodynamic effects. After N omega-nitro-L-arginine methyl ester (L-NAME), baseline CD fell (P < 0.01) to 3.35 +/- 0.08 mm but CBF was not significantly altered (36 +/- 5 ml min-1). CBF increases caused by adenosine were smaller (17 +/- 2 ml min-1, P < 0.05) and CD responses were nearly abolished (0.02 +/- 0.01 mm, P < 0.01). I.c. Ro 61-1790, an ETA receptor blocker, given after L-NAME did not significantly influence baseline CBF (36 +/- 5 ml min-1) but increased (P < 0.01) CD to 3.45 +/- 0.09 mm. CBF responses to adenosine were not significantly altered by Ro 61-1790 but CD responses (0.10 +/- 0.01 mm) were partially restored (P < 0.01). In contrast, blockade of ETB receptors with Ro 46-8443 after L-NAME had no further effects on CD and CBF responses to adenosine. ETA receptor-mediated effects limit flow-dependent dilation of large epicardial coronary arteries in conscious dogs. Suppression of the L-arginine/NO-dependent pathway with L-NAME reveals significant ET-dependent effects.
ISSN:0008-6363
1755-3245
DOI:10.1016/S0008-6363(99)00366-1