ROLE OF ENDOGENOUS ANGIOTENSIN-II ON SYMPATHETIC REFLEXES IN CONSCIOUS RABBITS

In the present study we sought to determine the contribution of endoge nous brain stem angiotensin to renal sympathetic reflexes in conscious rabbits. Initial studies determined the subtype of receptor involved in the presser response to angiotensin II (ANG II) administration into the fourth ventricle (4V). The AT(1) antagonist losartan (0.001-10 mu g 4V) had no effect on blood pressure alone but caused a dose-depende nt blockade of the presser effect of ANG II, with complete blockade pr oduced by 10 mu g, an effect that lasted for at least 3 h. The AT(2) a ntagonist PD-123319 (0.1-1,000 mu g and vehicle had no effect on the A NG II presser response. The effect of losartan (10 mu g) on the barore ceptor, chemoreceptor, and trigeminal reflexes was examined in eight r abbits that had been implanted with 4V catheters and an electrode for recording renal sympathetic nerve activity (RSNA) 1 wk earlier. Barore flex assessments were made during normoxia and two conditions of hypox ia (10% O-2 and 10% O-2 + 3% CO2) before and after 10 mu g losartan or vehicle, on separate experimental days. During normoxia and hypoxia CO2 losartan increased resting RSNA, the range, and upper plateau of the RSNA-MAP baroreflex curves. By contrast the marked increase in RSN A due to activation of trigeminal afferents was not affected by losart an. In conclusion the effect of losartan to increase RSNA activity in conscious rabbits, particularly during hypoxia and baroreceptor unload ing, suggests that endogenous ANG II via AT(1) receptors normally inhi bits renal sympathetic baroreceptor and chemoreceptor reflexes.