Angiotensin II response in afferent arterioles of mice lacking either the endothelial or neuronal isoform of nitric oxide synthase

The aim of the study is to evaluate the impact of nitric oxide (NO) produced by endothelial NO synthase (eNOS) and neuronal NOS (nNOS) on the angiotensin II response in afferent arterioles (Af). Dose responses were assessed for angiotensin II in microperfused Af of mice homozygous for disruption of the eNOS gene [ eNOS(-/-)], or nNOS gene [ nNOS(-/-)], and their wild-type controls, eNOS(+/+) and nNOS(+/+). Angiotensin II at 10(-8) and 10(-6) mol/l reduced the lumen to 69% and 68% in eNOS(+/+), and to 59% and 50% in nNOS(+/+). N-G-nitro-L-arginine methyl ester (L-NAME) did not change basal arteriolar diameters, but augmented angiotensin II contraction, reducing diameters to 23% and 13% in eNOS(+/+), and 7% and 10% in nNOS(+/+) at 10(-8) and 10(-6) mol/l. The response to angiotensin II was enhanced in nNOS(-/-) mice (41% and 25% at 10(-8) and 10(-6) mol/l) and even more enhanced in eNOS(+/+) mice (12% and 9%) compared with nNOS(+/+) and eNOS(+/+). L-NAME led to complete constriction of Af in these groups. Mediato-lumen ratios of Af did not differ between controls and gene-deficient mice. mRNA expression of angiotensin II receptor types 1A and 1B and type 2 also did not differ. The results reveal that angiotensin II-induced release of NO from both eNOS and nNOS significantly contributes to the control of Af. Results also suggest that eNOS-derived NO is of greater importance than nNOS-derived NO in this isolated arteriolar preparation.

Steege, Andreas (författare)
Lai, En YinUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)enlai087 (författare)
Brinkmann, Jan Ole (författare)
Kupsch, Eckehardt (författare)
Spielmann, Nadine (författare)
Gericke, Adrian (författare)
Skalweit, Angela (författare)
Stegbauer, Johannes (författare)
Persson, Pontus B (författare)
Seeliger, Erdmann (författare)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

Ingår i:American Journal of Physiology. Regulatory Integrative and Comparative Physiology: American Physiological Society294:2, s. R429-R4370363-61191522-1490

Av författaren/redakt...: Patzak, Andreas; Steege, Andreas; Lai, En Yin; Brinkmann, Jan O ...; Kupsch, Eckehard ...; Spielmann, Nadin ...; visa fler...; Gericke, Adrian; Skalweit, Angela; Stegbauer, Johan ...; Persson, Pontus ...; Seeliger, Erdman ...; visa färre...

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