title: Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade.
abstract: We tested whether the alpha 1- and alpha 2-blocking agent phentolamine can be used to assess the contribution of alpha-adrenergic constriction in circulatory control. In 15 conscious dogs at rest, phentolamine (2 mg/kg i.v.) caused hypotension (-17 mm Hg mean arterial pressure), vasodilation (-29% total peripheral resistance), tachycardia, and an increase in cardiac output, oxygen consumption, and plasma catecholamines. Following beta-adrenoceptor blockade (2 mg/kg i.v. nadolol), phentolamine still produced hypotension and increased plasma catecholamine levels, but neither vasodilation nor augmented oxygen consumption. During beta-blockade, phentolamine caused a 28-fold decrease in the vasoconstrictor response to norepinephrine infusions. An equihypotensive dosage of the alpha 1-adrenoceptor blocking agent prazosin (1.2 mg/kg i.v.) did not elevate heart rate, cardiac output, plasma catecholamines, or oxygen consumption. The prazosin-induced vasodilation was not attenuated by prior beta-blockade, in contrast to the phentolamine-induced vasodilation. It is concluded that phentolamine increased catecholamine release by presynaptic alpha 2-blockade, thereby suppressing the autoinhibition of transmitter release. This excess of catecholamines causes a rise of oxygen consumption and vasodilation by beta-adrenergic stimulation. Under beta-blockade, this excess competitively counteracts the postsynaptic vascular alpha-blockade. The combination of pre- and postsynaptic effects invalidates the use of phentolamine in the assessment of alpha-adrenoceptor-mediated vasoconstrictor tone.
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002395:Catecholamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine