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Involvement of beta 2-adrenoceptor-mediated mechanisms in the cardiovascular responses to alpha 1- and alpha 2-adrenoceptor antagonism in conscious, unrestrained, Long Evans and Brattleboro rats.

1. Intra-arterial blood pressures and heart rates were recorded in conscious, unrestrained, Long Evans and Brattleboro rats receiving sequential, continuous administrations of selective alpha 1- (prazosin) and alpha 2- (idazoxan) adrenoceptor antagonists. The same protocols were also run in the presence of ICI 118551 (a selective antagonist of beta 2-adrenoceptors). 2. Prazosin and idazoxan caused large, but transient, hypotensions in Long Evans and Brattleboro rats. In the continued presence of both drugs there were marked, intermittent, depressor episodes and tachycardias in both strains of rat. 3. In the presence of low or high doses of ICI 118551 the hypotensive responses to prazosin and idazoxan were markedly reduced in both strains of rat and blood pressures showed little variability, although intermittent tachycardias still occurred. 4. In adrenal-demedullated Long Evans rats, the hypotensive responses to prazosin and idazoxan were attenuated and in the presence of both drugs, blood pressure was relatively steady, although intermittent tachycardias still occurred. 5. In the presence of prazosin and idazoxan, when a depressor episode was not occurring, administration of captopril caused hypotension in Long Evans and Brattleboro rats. In the latter, the reduction in blood pressure was sustained, whereas there was a recovery in blood pressure in Long Evans rats. This recovery was punctuated by depressor episodes, and was abolished by a V1-receptor antagonist (d(CH2)5DAVP). 6. Long Evans rats given two primed doses of the non-selective alpha-adrenoceptor antagonist, phentolamine, exhibited variation in blood pressure similar to that seen in the presence of prazosin and idazoxan. As in the latter case, blood pressure variability was inhibited by the beta 2-adrenoceptor antagonist, ICI 118551. 7. Administration of idazoxan into a lateral ventricle in Long Evans rats receiving phenoxybenzamine intravenously did not cause blood pressure instability. However, intravenous administration of idazoxan in the same animals produced intermittent depressor episodes and tachycardias similar to those seen in the presence of prazosin and idazoxan. 8. The simplest explanation of the results is that beta 2-adrenoceptor-mediated depressor mechanisms contribute to the hypotensive responses to alpha 1- and alpha 2-adrenoceptor antagonism. Furthermore, in the presence of adequate peripheral alpha 1- and alpha 2-adrenoceptor antagonism, blood pressure may be maintained by the renin-angiotensin system and vasopressin (although it is only when the former system has been antagonized that a clear-cut pressor action of vasopressin is apparent). Under these conditions, blood pressure maintenance is interrupted by intermittent depressor episodes that are largely due to adrenal medullary activation.