Role of the postsynaptic alpha(2)-adrenergic receptor subtypes in catecholamine-induced vasoconstriction

Catecholamines induce direct vasoconstriction mediated by postsynaptic alph a-adrenergic receptors (alpha-ARs) of both the alpha(1) and alpha(2) type. To evaluate the contribution of each alpha(2)-AR subtype (alpha(2A), alpha( 2B), and alpha(2C)) to this function, we used groups of genetically enginee red mice deficient for the gene to each one of these subtypes and compared their blood pressure (BP) responses to their wild-type counterparts. Blood pressure responses to a bolus of norepinephrine (NE) were assessed before a nd after sequential blockade of alpha(1)-ARs with prazosin and alpha(2)-ARs with yohimbine. The first NE bolus elicited a brief 32 to 44 mm Hg BP rise (p < 0.001 from baseline) in all six groups. Prazosin decreased BP by 23 t o 33 mm Hg in all groups, establishing a new lower baseline. Repeat NE at t hat point elicited lesser but still significant (p < 0.001) brief presser r esponses between 32% and 45% of the previous BP rise in five of the six gro ups. Only the alpha(2A)-AR gene knockouts differed, responding instead with a 20-mm Hg fall in BP, a significant change from baseline (p < 0.001) and different from the presser response of their wild-type counterparts (p < 0. 001). The addition of yohimbine produced no further BP change in the five g roups, but it did produce a small 7.5-mm Hg fall (p < 0.05) in the alpha(2A )-AR knockouts. Norepinephrine bolus during concurrent alpha(1) and alpha(2 )-AR blockade produced significant (p < 0.001) hypotensive responses in all subgroups, presumably attributable to unopposed stimulation of beta(2)-vas cular wall ARs. We conclude that the alpha(2)-AR-mediated vasoconstriction induced by catecholamines is attributable to the alpha(2A)-AR subtype becau se mice deficient in any one of the other subtypes retained the capacity fo r normal vasoconstrictive responses. However, the alpha(1)-ARs account for the major part (as much as 68%) of catecholamine-induced vasoconstriction. (C) 2000 Elsevier Science Inc. All rights reserved.