Norepinephrine-induced beta 1-adrenergic peripheral vasodilation in conscious dogs.
Norepinephrine (NE) elicits alpha-adrenergic vasoconstriction and beta 1-adrenergic increases in heart rate and myocardial contractility. To determine whether NE can also elicit peripheral beta 1-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 TPR 60 +/- 5% from 0.058 +/- 0.007 mmHg X ml-1 X min and increased cardiac output 55 +/- 11% from 2,159 +/- 188 ml/min. beta 1-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 beta 2-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 alpha-adrenergic receptor blockade, either administration of NE or release of endogenous NE elicits potent peripheral vasodilation, which appears to involve a beta 1-adrenergic receptor mechanism.
Vatner
S F
SF
Knight
D R
DR
Hintze
T H
TH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D006584:Hexamethonium Compounds; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D018738:Hexamethonium; D001262:Atenolol; D007545:Isoproterenol; C009118:pirbuterol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine