Role of NADPH oxidase and iNOS in vasoconstrictor responses of vessels from hypertensive and normotensive rats

Background and purpose: To analyse the influence of hypertension in the modulation induced by inducible NOS (iNOS)‐derived NO and superoxide anion (O 2 •− ) of vasoconstrictor responses and the sources of O 2 •− implicated. Experimental approach: Vascular reactivity experiments were performed in segments of aorta from normotensive, Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR); protein and mRNA expressions were respectively measured by western blot and quantitative reverse transcription‐polymerase chain reaction and O 2 •− production was evaluated by ethidium fluorescence. Key results: The contractile responses to phenylephrine (1 n M –30 μ M ) and 5‐hydroxytryptamine (0.1–100 μ M ) were greater in aortic segments from SHR than WKY. The selective iNOS inhibitor, 1400W (10 μ M ), increased the phenylephrine contraction only in WKY segments; however, iNOS protein and mRNA expressions were greater in aorta from SHR than WKY. Superoxide dismutase (SOD, 150 U ml −1 ) reduced phenylephrine and 5‐hydroxytryptamine responses only in aorta from SHR; the NAD(P)H oxidase inhibitor apocynin (0.3 m M ) decreased phenylephrine and 5‐hydroxytryptamine responses more in vessels from SHR than WKY. Co‐incubation with SOD plus 1400W potentiated the phenylephrine and 5‐hydroxytryptamine responses more in segments from SHR than WKY. O 2 •− production was greater in aorta from SHR than WKY; apocynin abolished this difference. Conclusions and implications: Increased O 2 •− formation from NADP(H) oxidase in vessels from hypertensive rats contributes to the vasoconstrictor responses and counteract the increase of NO from iNOS and the consequent modulation of these responses. British Journal of Pharmacology (2008) 153 , 926–935; doi: 10.1038/sj.bjp.0707575 ; published online 12 November 2007