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 (Ang II)-type 1 (AT,) receptor antagonist, on the responses evoked by Ang II and L-glutamate (L-GIu) in the rostral ventrolateral medulla (RVLM). Adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were anesthetized with halothane and artificially ventilated. Responses of mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nerve activity (SNA) to microinjection of Ang II (100 pmol) or L-Glu (2 nmol) into the RVLM were examined following microinjection of losartan (10 pmol-10 nmol). Ang II increased MAP (16 +/- 1 mmHg in SHR and 16 +/- 1 mmHg in WKY) and SNA (9 +/- 1% and 10 +/- 1%, respectively), which were significantly (P < 0.01) attenuated by pretreatment with losartan (100 pmol-l0 nmol) in both strains. In addition, the presser and sympathoexcitatory responses evoked by L-Glu were attenuated by losartan in a dose-dependent manner. The increases of MAP evoked by L-Glu (53 +/- 6 mmHg in SHR and 39 +/- 3 mmHg in WKY) were suppressed to 5 +/- 3 mmHg (P < 0.01) and 4 +/- 2 mmHg (P < 0.01), respectively, in the presence of 10 nmol of losartan. The increase of SNA was also-markedly inhibited by higher doses of losartan. The cardiovascular responses evoked by L-Glu, however, were not attenuated by pretreatment with either 1 nmol of [Sar(1),Thr8]-Ang II or 10 nmol of potassium acetate, suggesting that the effect of losartan on L-Glu response may not be attributed to the blockade of Ang II receptor or to the high concentration of potassium. These results indicate that the AT, receptor is responsible, in part, for the vasomotor action of Ang II in the RVLM and losartan has an inhibitory effect on presser and sympathoexcitatory responses evoked by L-Glu by mechanisms other than those mediated by Ang II receptors.