Endothelin and angiotensin mediate most glomerular responses to nitric oxide inhibition

Background. Endothelin (ET) and angiotensin mediate glomerular responses to systemic nitric oxide (NO) inhibition. Acute systemic NO synthase (NOS) in hibition in the rat causes marked increases in both preglomerular (R-A) and efferent arteriolar (R-E) resistances and a fall in the glomerular capilla ry ultrafiltration coefficient (K-f). In contrast, local intrarenal NOS inh ibition increases R-A, but has no effect on R-E while producing a similar K -f lowering effect as seen with systemic NOS inhibition. These studies were designed to assess whether the increase in R-E during systemic NOS inhibit ion is mediated by endogenous ET and whether angiotensin II (Ang II) also c ontributes. Methods. Micropuncture measurements were made before and during acute syste mic NOS inhibition with N-monomethyl L-arginine (NMA) alone, NMA + the nonp eptide ETA and ETB receptor antagonist, bosentan, NMA + the Ang II type 1 r eceptor blocker, losartan, and NMA during combined bosentan and losartan. Results. The falls in single nephron glomerular filtration rate (SNGFR) and glomerular plasma flow seen with systemic NOS inhibition were prevented by concomitant administration of bosentan and losartan alone and in combinati on. The increases in systemic blood pressure (BP), glomerular BP (P-GC), R- A, and R-E and the reduction in K-f seen with systemic NOS inhibition were attenuated by either bosentan or losartan. An attenuation in the elevation in total renal vascular resistance seen with systemic NOS inhibition was al so observed with bosentan. Combined ET and Ang II type 1 blockade completel y prevented the increase in systemic BP, P-GC, and R-E and the fall in K-f with systemic NOS inhibition, leaving only a very attenuated rise in RA Conclusions. These findings suggest that endogenous ET and Ang II partially mediate the glomerular hemodynamic responses (including the increased R-E) to acute systemic NOS inhibition. The actions of ET and Ang II are mainly additive, and almost all of the vasoconstrictor responses to acute NOS inhi bition are prevented when both vasoconstrictor systems are blocked.