Absence of functioning α-adrenergic receptors in mature canine coronary collaterals

Abstract

To determine if mature coronary collateral vascular smooth muscle contains functioning α-adrenergic receptors, we studied 13 dogs, 6-10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the α-adrenergic agonist methoxamine (n = 6) or the α2-adrenergic agonist clonidine (n = 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 ± 0.06 to 0.39 ± 0.06 mm Hg x min/ml per 100 g (resistance units) during infusion of 10-5M methoxamine (p < 0.05). In contrast transcollateral resistance averaged 0.24 ± 0.02 resistance units under control conditions and did not change during methoxamine infusion. In the hearts that received clonidine, normal zone resistance averaged 0.24 ± 0.03 resistance units and increased to 0.39 ± 0.07 resistance units (p < 0.05) with the highest dose of clonidine administered (10-5 M). Transcollateral resistance averaged 0.17 ± 0.03 resistance units during control conditions and did not change with clonidine infusion. In separate studies isometric tension development by the left anterior descending and coronary collateral vessels was examined in organ baths. The left anterior descending coronary artery demonstrated dose-dependent constriction to phenylephrine (peak response 22 ± 5% of the response to 100 mM KCl). Clonidine produced weak constrictor responses in the left anterior descending coronary artery (5 ± 2.5% maximal KCl response). In contrast, neither phenylephrine nor clonidine produced responses in mature collaterals. We also examined responses of mature collateral vessels to nonadrenergic agonists. In the vascular ring preparation the mature collaterals developed tension in the presence of KCl (2.3 ± 0.9 g), prostaglandin F(2α) (16 ± 8% of the KCl responses), and vasopressin (90 ± 30% of the KCl response). In adenosine-vasodilated hearts, pharmacologic doses of vasopressin caused a two-fold increase in transcollateral resistance. Thus, these studies performed on intact hearts and isolated vascular rings demonstrate that mature coronary collaterals do not contain functioning α-adrenergic receptors. Consequently, mature coronary collateral resistance is not regulated by α-adrenergic neurohumoral mechanisms.