ROLE OF ENDOGENOUS ENDOTHELIN AND NITRIC-OXIDE IN TUBULOGLOMERULAR FEEDBACK

To elucidate the roles of endogenous endothelin (ET) and nitric oxide (NO) in tubuloglomerular feedback (TGF), the effects of FR139317, a sp ecific ET-A receptor antagonist, and N-G-nitro-L-arginine (L-NNA), a N O synthase inhibitor on TGF were studied in Sprague-Dawley rats. FR139 317 (1.5 mg/kg/hr i.v.) reversed the systemic presser and renal vasoco nstrictor responses induced by ET-1 (2 nmol/kg/hr i.v.), but did not a lter the early proximal flow rate (EPFR) reduction in response to a lo op perfusion with an artificial tubular fluid at 40 nl/min (47 +/- 3 v s. 47 +/- 3% in controls). L-NNA (0.2 mg/kg + 2 mu g/kg/min i.v.) had no effect on systemic blood pressure (BP), renal hemodynamics or EPFR measured at zero perfusion (32 +/- 2 vs. 31 +/- 2 nl/min in controls), but enhanced the EPFR reduction during loop perfusion to 77 +/- 3%. L oop perfusion with 10(-3) M L-NNA in perfusate also increased the EPFR reduction to 70 +/- 7%. In conclusion, inhibition of NO synthesis enh ances the TGF-mediated reduction of nephron GFR. This indicates an act ive participation of endogenous NO in the control of afferent arteriol ar tone. Endogenous ET does not influence TGF via the ET-A receptor.