Heterogeneous microvascular coronary α-adrenergic vasoconstriction

Abstract

We tested the hypothesis that humoral or neurogenic α-adrenergic activation in the coronary circulation would produce heterogeneous vascular reactions. To accomplish this, the epicardial coronary microcirculation was viewed through an intravital microscope using stroboscopic epi-illumination. Microvascular diameters were measured under control conditions during β-adrenergic blockade (propranolol 1 mg/kg) and β-adrenergic blockade with pacing; during coronary α-adrenergic activation in the presence of β-adrenergic blockade with three doses of norepinephrine infusion (0.1, 0.5, and 1.0-2.0 μg/kg/min) or three frequencies of bilateral stellate nerve stimulation (2, 10, and 20 Hz); and during combined α- and β-adrenergic blockade (phentolamine 2 mg/kg and propranolol 1 mg/kg). Diameters of both arterial and venous vessels were reduced during β-adrenergic blockade but returned back to baseline with pacing. At the lowest level of norepinephrine infusion or frequency of bilateral stellate stimulation, microvessel constriction was not observed. At the highest doses of norepinephrine a -5.1 ± 0.9% (1.0-2.0 μg/kg/min) and a -4.0 ± 1.1% (0.5 μg/kg/min) decrease in diameter of arterial vessels greater than 100 μm in diameter were observed (p < 0.05). At 10 Hz and 20 Hz of stellate stimulation, diameter decreased by -4.8 ± 1.9% and -4.4 ± 2.1%, respectively, in these relatively large vessels. Small coronary arterioles (<100 μm diameter) dilated significantly during the highest levels of nerve stimulation (9.2 ± 2.5% increase in diameter) or infusion rate of norepinephrine (13.6 ± 2.7% increase in diameter) (p < 0.05). These constrictor and dilator responses were abolished following combined α- and β-adrenergic blockade. Norepinephrine infusion resulted in a decrease in diameter of coronary veins and venules (7.2 ± 1.3%) (p < 0.05), whereas stellate stimulation did not significantly reduce venous and venular diameters. In summary, the coronary venous and venular vasculature responds to α-adrenergic activation from circulating norepinephrine but is not affected by stellate stimulation. In contrast, stellate stimulation and norepinephrine infusion elicit similar responses in the coronary arterial and arteriolar microvasculature. Constriction occurs in vessels greater than 100 μm in diameter, whereas dilation predominates in vessels less than 100 μm in diameter. Such heterogeneous arterial responses would undoubtedly result in a redistribution of coronary vascular resistance toward larger coronary arteries and arterioles.