POSTJUNCTIONAL REGULATION BY ANGIOTENSIN-II OF ALPHA(1)-ADRENOCEPTOR-MEDIATED PRESSER RESPONSES IN THE RAT

The effects of angiotensin II on the vasopressor responses to the sele ctive alpha(1)-adrenoceptor agonist, phenylephrine, in intact and symp athectomized rats were investigated. Infusion of angiotensin II at sub pressor doses significantly enhanced the presser effects of phenylephr ine in intact rats. We also found that in the chemically sympathectomi zed rat, where prejunctional sympathetic function is impaired, the eff ects of angiotensin II infusion on the presser effects of phenylephrin e were similar to those obtained in intact rats. Furthermore, pretreat ment with valsartan -(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-valine),a new selective angiotensin AT(1) receptor antagonist, antagonized the effects of angiotensin II on phenylephrine-mediated presser responses, whereas the administration of the selective angiotensin AT(2) recepto r antagonist, PD 123319 tetrahydro-1H-imidazo[4,5-c]-pyridine-6-carbox ylic acid, ditriflouroacetate, monohydrate), injected in bolus doses o f 100 mu g/kg, did not antagonize the enhancing effect of angiotensin II. Collectively, these data suggest that angiotensin II modulates the response to phenylephrine primarily at a postjunctional level through the activation of angiotensin AT(1) receptors and that the suggested prejunctional facilitation mediated by angiotensin receptors is quanti tatively much less important in the intact animal.