Interaction of angiotensin II and nitric oxide in isolated perfused afferent arterioles of mice

The present study was performed to evaluate angiotensin II (Ang II)-nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mi ce that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed fo r the NO precursor L-arginine (n = 4), NO inhibitor NG-nitro-L-arginine met hyl ester (L-NAME, n = 5), L-NAME after pretreatment with L-arginine (n = 5 ), Ang II (n = 8), and Ang II after pretreatment with L-NAME (n = 7). Acute administration of L-arginine and L-NAME (both in doses from 10(-6) to 10(- 3) mol/L) did not change arteriolar diameter. Moreover, pretreatment with L -arginine did not change the response to L-NAME. However, Ang II, applied i n doses of 10(-12), 10(-10), 10(-8), and 10(-6) mol/L, significantly reduce d the lumen to 66.5 +/- 7.0% and 62.2 +/- 8.0% at 10(-8) and 10(-6) mol/L A ng II, respectively. The contraction was augmented after L-NAME pretreatmen t (19.5 +/- 13.6% and 25.5 +/- 10.2% at 10(-8) and 10(-6) mol/L Ang II, res pectively). In eNOS (-/-) mice (n = 8), the response to Ang II also was enh anced (9.1 +/- 6.0% and 11.2 +/- 8.2% at 10(-8) and 10(-6) mol/L Ang II, re spectively). Female mice did not differ from male mice in their reactivity to Ang II (n = 9) and Ang II + L-NAME pretreatment (n = 11). The study show s that (1) it is feasible to microperfuse mouse Af, (2) the basal productio n of endothelial NO is very low and not inducible by L-arginine in Af of mi ce, and (3) a counteracting effect of NO is initiated by Ang II. High Ang I I sensitivity in eNOS (-/-) mice underscores the considerable role of endot helial-derived NO to balance Ang II vasoconstriction in Af.