Endothelin-dependent effects limit flow-induced dilation of conductance coronary vessels after blockade of nitric oxide formation in conscious dogs.
OBJECTIVE
To determine whether endothelin (ET)-dependent effects limit shear stress-induced dilation of large epicardial coronary arteries after blockade of nitric oxide (NO) formation.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Parent
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Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
Lavallée
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D000241:Adenosine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011725:Pyridines; D011743:Pyrimidines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles; D014665:Vasodilator Agents / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000241:Adenosine; D004146:Dioxanes; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; D014665:Vasodilator Agents; C099180:Ro 46-8443; D000096926:Benzenesulfonamides; C109641:clazosentan