RUOLO DELL'ENDOTELINA E DELL'ENDOTHELIUM-DERIVED RELAXING FACTOR NELLA MICROCIRCOLAZIONE RENALE

In order to investigate the role of Endothelin (ET) and Endothelium-derived relaxing factor (EDRF) on control of renal vascular tone under basal conditions, we tested the effects of intravenous infusion of rabbit anti-human ET-1/3 antibodies (a-ET-1/3) and competitive inhibitor of nitric oxide (NO) synthase NG-nitro-L-arginine-methyl-ester (L-NAME) on the split hydronephrotic kidney of rats. A 25-min intravenous infusion of a-ET-1/3 (4.0·10^-13 mol·Kg^-1·min^-1) induced a time-dependent vasodilatation of larger pre-glomerular vessels, pronounced in distal arcuate (+16.5%) and proximal interlobular arteries (+18.6%), and increased glomerular blood flow (GBF) by 32%. Inhibition of EDRF/NO synthesis by intravenous infusion of the EDRF inhibitor L-NAME (2 mg·Kg^-1) induced a marked vasoconstriction of proximal (-17.1%) and distal (-7.1%) arcuate arteries as well as efferent arterioles (-20.1%), and a decrease of GBF by 43%. Inhibition of both systems by infusion of a-ET-1/3 followed after 10 min by a bolus injection of L-NAME induced vasoconstriction of efferent arteriole by 19.5% whereas diameters of preglomerular vessels remained unchanged. GBF decreased by 13%. Our observations by direct intravital microscopy with combined inhibition of ET effects and EDRF/NO synthesis suggest a physiological role of EDRF and ET in control of basal vascular tone in larger preglomerular vessels, whereas the tone of the efferent arteriole appears to be predominantly regulated by the action of EDRF/NO.