Nitric oxide counteracts angiotensin II induced contraction in efferent arterioles in mice.

Efferent arterioles (Ef) are one of the final control elements in glomerular haemodynamics. The influence of nitric oxide (NO) on Ef remains ambiguous.To test the hypothesis that endothelial NO plays an important role in this context, afferent arterioles (Af) and Ef of wild-type mice (WT), and Ef of mice lacking the endothelial NO synthetase [eNOS(-/-)] were perfused. Perfusion was performed in Ef via Af (orthograde) as well as from the distal end of Ef (retrograde), which provides an estimate for the importance of substances derived from the glomerulus. Angiotensin II (Ang II) was added in doses ranging from 10(-12) to 10(-6) mol L(-1) to the bath solution.Ang II reduced the luminal diameter of Af to 68 +/- 7 and in Ef to 55 +/- 8% during orthograde, and to 35 +/- 6% during retrograde perfusion (10(-6) mol L(-1) Ang II) in WT. Pre-treatment with N(G)-Nitro-L-arginine-methylester (l-NAME) (10(-4) mol L(-1)) increased the Ang II sensitivity in retrograde (17 +/- 9%) and orthograde perfused Ef (19 +/- 9%). The Ang II sensitivity was enhanced in eNOS(-/-) mice compared with WT, too. Already at a dose of Ang II 10(-9) mol L(-1), luminal diameters diminished to 8 +/- 7 and 7 +/- 4%.The increased Ang II sensitivity during L-NAME pre-treatment and in eNOS(-/-) mice indicates a strong counteraction of endothelial derived NO on Ang II induced contraction in Ef. Moreover, Ef are similarly sensitive to Ang II during either retrograde or orthograde perfusion in the absence of NO effects, suggesting that NO mediates, at least in part, the action of potential vasodilatory substances from the glomerulus.