Norepinephrine-induced β₁-adrenergic peripheral vasodilation in conscious dogs

Norepinephrine (NE) elicits α-adrenergic vasoconstriction and β₁-adrenergic increases in heart rate and myocardial contractility. To determine whether NE can also elicit peripheral β₁-adrenergic vasodilation, conscious dogs were studied after recovery from instrumentation for the measurement of cardiac output, arterial pressure, and left ventricular (LV) pressure and calculations of LV dP/dt and total peripheral resistance (TPR). NE, after pretreatment with hexamethonium and phentolamine, reduced mean arterial pressure 40 ± 5% from 117 ± 9 mmHg and TRP 60 ± 5% from 0.058 ± 0.007 mmHg·ml^-1·min and increased cardiac output 55 ± 11% from 2,159 ± 188 ml/min. β₁-Adrenergic blockade with atenolol reversed the vasodilation induced by NE completely, while at this time isoproterenol was still able to reduce peripheral resistance further, by 67 ± 7%, indicating that β₂-adrenergic receptors were not blocked. Administration of phentolamine to intact dogs caused a fall in mean arterial pressure (23 ± 5%) and TPR (34 ± 5.4%) and an endogenous increase in plasma NE (2,987 ± 905 pg/ml) and epinephrine (584 ± 92 pg/ml). These increases in cardiac output and decreases in TPR were also reversed by atenolol (0.5 mg/kg). Moreover, this dose of atenolol blocked the increases in iliac blood flow induced by local injection of NE in the limb. Thus, in the presence of α-adrenergic receptor blockade, either administration of NE or release of endogenous NE elicits potent peripheral vasodilation, which appears to involve a β₁-adrenergic receptor mechanism.