REGIONAL HETEROGENEITY OF ENDOTHELIUM-DEPENDENT VASODILATATION IN THE RABBIT KIDNEY

1. Regional heterogeneity of endothelial function exists but its role in the local regulation of vascular tone is uncertain. This heterogeneity may be very important in the control of the glomerular filtration rate (GFR) in which the differential tone in the afferent and efferent arterioles is crucial. 2. When an endothelium-independent vasodilator, prostacyclin (PGI2) or nitroprusside, was infused into anaesthetized rabbits there were dose-dependent falls in both mean arterial pressure (MAP) and GFR; PGI2 (0.4 nmol kg-1 min-1) altered MAP and GFR by -18.5 +/- 3.6% (mean +/- S.E.M.) and -37.7 +/- 13.3% respectively and nitroprusside (30 nmol kg-1 min-1) by -29.7 +/- 3.1% and -67.0 +/- 2.4%. In contrast infusion of an endothelium-dependent vasodilator, acetylcholine (ACh) or substance P, produced dose-dependent decreases in MAP but dose-dependent increases in GFR; ACh (10 nmol kg-1 min-1) -15.1 +/- 2.0% and +43.8 +/- 16.5% and substance P (30 nmol kg-1 min-1) -18.7 +/- 1.9% and +45.3 +/- 23.1% respectively. The effects of endothelium-dependent and independent vasodilators on GFR was significantly different (p < 0.005). 3. Simultaneous administration of indomethacin, Methylene Blue or NG-monomethyl-L-arginine (L-NMMA), inhibitors of cyclo-oxygenase and endothelium-derived relaxing factor (EDRF) respectively, attenuated or reversed the effect of ACh (10 nmol kg-1 min-1) on MAP and GFR. 4. These data suggest that endothelium-dependent vasodilatation in the kidney has a heterogeneous effect on the renal microvasculature, exerting a preferential effect on afferent glomerular arterioles and thereby preserving GFR despite the fall in MAP. If correct, this has important implications for the regulation of GFR.