α₁ and α₂-adrenoceptor-mediated pressor and chronotropic effects in the rat and rabbit

In pithed rats or rabbits the pressor effect s of catecholamines or sympathetic nerve stimulation can be reduced by "selective" antagonists of α₁, (prazosin) or α₂ (rauwolscine) adrenoceptors. In rabbits the pressor response to low and high doses of intravenous noradrenahne were due predominantly to α₂-and α₁-adrenoeeptors, respectively. With low frequencies of vasopressor nerve stimulation, the response could be blocked by each antagonist, suggesting either that both receptors were involved or that the receptors were unlike those activated by circulating noradrenahne. With higher frequencies, prazosin reduced responses but left a residual response which could not he eliminated by rauwolscine; this could indicate a "non-α" junctional activation: rauwolscine. on its own. could increase responses to high frequencies indicating blockade of prejunctional α-mediated feedback. In rats, acid- base balance was critical for the activation of α¹- and α₂-adrenoceptors. The effects of the antagonists indicated that adrenaline acts predominantly through α₁-adrenoceptors at high pH. but that the influence of α₂, increased as pH falls. Also, as pH fell, the pressor effects of phenylephrine and xylazine decreased and increased, respectively, suggesting that the mechanism of the change lies at the receptors or a subsequent stage in excitation-contraction coupling. These results are discussed in relation to current hypotheses on the heterogeneity of postjunctional adrenoceptors.