Interaction of Angiotensin II and Nitric Oxide in Isolated Perfused Afferent Arterioles of Mice

Abstract . The present study was performed to evaluate angiotensin II (Ang II)—nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mice that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed for the NO precursor L-arginine ( n = 4), NO inhibitor NG-nitro-L-arginine methyl 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 in doses of 10 -12 , 10 -10 , 10 -8 , and 10 -6 mol/L, significantly reduced the lumen to 66.5 ± 7.0% and 62.2 ± 8.0% at 10 -8 and 10 -6 mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 ± 13.6% and 25.5 ± 10.2% at 10 -8 and 10 -6 mol/L Ang II, respectively). In eNOS (-/-) mice ( n = 8), the response to Ang II also was enhanced (9.1 ± 6.0% and 11.2 ± 8.2% at 10 -8 and 10 -6 mol/L Ang II, respectively). 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 shows that ( 1 ) it is feasible to microperfuse mouse Af, ( 2 ) the basal production of endothelial NO is very low and not inducible by L-arginine in Af of mice, and ( 3 ) a counteracting effect of NO is initiated by Ang II. High Ang II sensitivity in eNOS (-/-) mice underscores the considerable role of endothelial-derived NO to balance Ang II vasoconstriction in Af.