Pharmacological profile of depressor response elicited by sarthran in rat ventrolateral medulla

Injection of sarthran, an angiotensin receptor antagonist, bilaterally into the rostral ventrolateral medulla (RVLM) of alpha -chloralose-anesthetized rats decreases arterial pressure (AP) to the same extent as total autonomi c blockade. This response is not reproduced by selective AT(1) antagonists. To examine the pharmacological profile of the response elicited by [Sar(1) , Thr(8)]ANG II (sarthran), the ability of angiotensin analogs to inhibit t he effect of sarthran injected into the RVLM was tested. Coinjection of ang iotensin II (ANG II) prevented the sarthran-evoked decrease in AP, but this action of ANG II was markedly attenuated by pretreatment of the RVLM with the aminopeptidase inhibitor amastatin. Coinjection of ANG(3-8) or a select ive agonist of AT(4) receptors prevented the effect of sarthran injected in to the RVLM. ANG(1-7) was also able to prevent the effect of sarthran. None of the angiotensin fragments tested substantially altered blood pressure w hen injected alone into the RVLM. These results suggest that the depressor action of sarthran injected into the RVLM is not dependent on ANG II recept ors, though the nature of the site or sites of action of sarthran within th e RVLM remains uncertain.