LOSARTAN, NONPEPTIDE ANGIOTENSIN-II TYPE-1 (AT(1)) RECEPTOR ANTAGONIST, ATTENUATES PRESSER AND SYMPATHOEXCITATORY RESPONSES EVOKED BY ANGIOTENSIN-II AND L-GLUTAMATE IN ROSTRAL VENTROLATERAL MEDULLA

We investigated the effect of losartan, a nonpeptide angiotensin II (A ng II)-type 1 (AT,) receptor antagonist, on the responses evoked by An g II and L-glutamate (L-GIu) in the rostral ventrolateral medulla (RVL M). Adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were anesthetized with halothane and artificially ventilated. Re sponses of mean arterial pressure (MAP), heart rate (HR) and splanchni c sympathetic nerve activity (SNA) to microinjection of Ang II (100 pm ol) or L-Glu (2 nmol) into the RVLM were examined following microinjec tion of losartan (10 pmol-10 nmol). Ang II increased MAP (16 +/- 1 mmH g in SHR and 16 +/- 1 mmHg in WKY) and SNA (9 +/- 1% and 10 +/- 1%, re spectively), which were significantly (P < 0.01) attenuated by pretrea tment with losartan (100 pmol-l0 nmol) in both strains. In addition, t he presser and sympathoexcitatory responses evoked by L-Glu were atten uated by losartan in a dose-dependent manner. The increases of MAP evo ked by L-Glu (53 +/- 6 mmHg in SHR and 39 +/- 3 mmHg in WKY) were supp ressed to 5 +/- 3 mmHg (P < 0.01) and 4 +/- 2 mmHg (P < 0.01), respect ively, in the presence of 10 nmol of losartan. The increase of SNA was also-markedly inhibited by higher doses of losartan. The cardiovascul ar responses evoked by L-Glu, however, were not attenuated by pretreat ment with either 1 nmol of [Sar(1),Thr8]-Ang II or 10 nmol of potassiu m acetate, suggesting that the effect of losartan on L-Glu response ma y not be attributed to the blockade of Ang II receptor or to the high concentration of potassium. These results indicate that the AT, recept or is responsible, in part, for the vasomotor action of Ang II in the RVLM and losartan has an inhibitory effect on presser and sympathoexci tatory responses evoked by L-Glu by mechanisms other than those mediat ed by Ang II receptors.