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

Abstract

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 10-6to 10-3mol/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 10-6mol/L, significantly reduced the lumen to 66.5 ± 7.0% and 62.2 ± 8.0% at 10-8and 10-6mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 ± 13.6% and 25.5 ± 10.2% at 10-8and 10-6mol/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 10-8and 10-6mol/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.