Novel nitric oxide synthase-dependent mechanism of vasorelaxation in small arteries from hypertensive rats

Kyu Tae Kang, Jennifer C. Sullivan, Jennifer M. Sasser, John D. Imig, Jennifer S. Pollock

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

To determine the mechanism(s) involved in vasorelaxation of small arteries from hypertensive rats, normotensive (NORM), angiotensin II-infused (ANG), high-salt (HS), ANG high-salt (ANG/HS), placebo, and deoxycorticosterone acetate-salt rats were studied. Third-order mesenteric arteries from ANG or ANG/HS displayed decreased sensitivity to acetylcholine (ACh)-induced vasorelaxation compared with NORM or HS, respectively. Maximal relaxations were comparable between groups. Blockade of Ca-activated K channels had no effect on ANG versus blunting relaxation in NORM (log EC50: -6.8±0.1 versus -7.2±0.1 mol/L). NO synthase (NOS) inhibition abolished ACh-mediated relaxation in small arteries from ANG, ANG/HS, and deoxycorticosterone acetate-salt versus blunting relaxation in NORM, HS, and placebo (% maximal relaxation: ANG: 2.7±1.8; ANG/HS: 7.2±3.2; NORM: 91±3.1; HS: 82.1±13.3; deoxycorticosterone acetate-salt: 35.2±17.7; placebo: 79.3±10.3), indicating that NOS is the primary vasorelaxation pathway in these arteries from hypertensive rats. We hypothesized that NO/cGMP signaling and NOS-dependent H2O2 maintains vasorelaxation in small arteries from ANG. ACh increased NOS-dependent cGMP production, indicating that NO/cGMP signaling is present in small arteries from ANG (55.7±6.9 versus 30.5±5.1 pmol/mg), and ACh stimulated NOS-dependent H2O2 production (ACh: 2.8±0.2 μmol/mg; Nω-nitro-L-arginine methyl ester hydrochloride+ACh: 1.8±0.1 μmol/mg) in small arteries from ANG. H2O2 induced vasorelaxation and catalase blunted ACh-mediated vasorelaxation. In conclusion, Ca-activated K channel-mediated relaxation is dysfunctional in small mesenteric arteries from hypertensive rats, and the NOS pathway compensates to maintain vasorelaxation in these arteries through NOS-mediated cGMP and H2O2 production.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalHypertension
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2007

Keywords

  • Aorta
  • Endothelium-dependent vasorelaxation
  • Hydrogen peroxide
  • Hypertension
  • Mesenteric arteries
  • NO

ASJC Scopus subject areas

  • Internal Medicine

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