It has been proposed that α-adrenoceptor vasoconstriction in coronary resistance vessels results not from α-adrenoceptors on coronary smooth muscle but from α-adrenoceptors on cardiac myocytes that stimulate endothelin (ET) release. The present experiments tested the hypothesis that the α-adrenoceptor-mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs (n = 10), the endothelin ETA/ETB receptor antagonist tezosentan (1 mg/kg iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the α-adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and α-adrenoceptor blockade results indicates that α-adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs, bolus intracoronary injections of the α-adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if α-adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||4 57-4|
|State||Published - Apr 2005|
- Coronary blood flow