Alterations of α-Adrenergic Modulations of Coronary Microvascular Tone in Dogs With Heart Failure

It remains unclear whether coronary microvascular response to α-adrenergic activation alters in chronic heart failure (CHF). We investigated the α-adrenergic receptor–mediated effects on coronary pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure model. The dogs studied were male (29 of 31) and the drugs were given intracoronary. The slope of CPFR during long diastole was evaluated as an index of coronary vascular resistance, during α 1- or α 2-adrenergic stimulation or inhibition under anesthesia in the baseline and failing state after 3 weeks of rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in the failing state from the baseline state. Neither α 1 nor α 2 stimulation changed the slope of CPFR in the baseline state. However, in the failing state, α 1 stimulation decreased the slope of CPFR by 23 ± 5% ( P < .05), whereas α 2 stimulation increased it by 73 ± 10% ( P < .05), which was nearly abolished by pretreatment with N G-nitro- l-arginine methyl ester. α 2-mediated vasodilatory action, presumably via endothelium-derived nitric oxide release, would be enhanced in the coronary microvascular bed, which may antagonize enhanced α 1-induced vasoconstriction in CHF.