ENDOTHELIUM-DERIVED RELAXING FACTOR NITRIC-OXIDE MODULATES ANGIOTENSIN-II ACTION IN THE ISOLATED MICROPERFUSED RABBIT AFFERENT BUT NOT EFFERENT ARTERIOLE

It has been reported that sensitivity to angiotensin II (Ang II) is hi gher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the inter action between Ang II and endothelium-derived relaxing factor/nitric o xide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrog rade perfusion) to eliminate influences of the Af-Art or glomerulus, r espectively. Ang II did not alter Af-Art luminal diameter until the co ncentration reached 10(-9) M, which decreased the diameter by 11+/-2.6 % (n = 11; P < 0.002). In contrast, Ef-Arts became significantly const ricted at concentrations as low as 10(-11) M with either perfusion. Su rprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10 (-8) M was significantly greater with retrograde perfusion (44+/-6.9%, 70+/-5.6%, and 74+/-4.1%, respectively; n = 5) than with orthograde p erfusion (16+/-4.2%, 25+/-2.9%, and 35+/-3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decrea sed the diameter to a greater extent in Af-Arts (22+/-3.0%; n = 11) co mpared to Ef-Arts with either orthograde (9.5+/-2.3%; n = 8) or retrog rade perfusion (1.2+/-2.1%; n = 6). With L-NAME pretreatment, Af-Art c onstriction induced by 10(-10) M (14+/-4.0%, n = 9) and 10(-9) M Ang I i (38+/-3.9%) was significantly greater compared to nontreated Af-Arts . In contrast, L-NAME pretreatment had no effect on Ang II-induced con striction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly wit h retrograde perfusion. Our results suggest that EDNO significantly mo dulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef- Arts, contributing to the differential sensitivity to Ang II.