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

Hypertension. 2007 Apr;49(4):893-901. doi: 10.1161/01.HYP.0000259669.40991.1e. Epub 2007 Feb 19.


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(2+)-activated K(+) channels had no effect on ANG versus blunting relaxation in NORM (log EC(50): -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 H(2)O(2) 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 H(2)O(2) production (ACh: 2.8+/-0.2 micromol/mg; N(omega)-nitro-l-arginine methyl ester hydrochloride+ACh: 1.8+/-0.1 micromol/mg) in small arteries from ANG. H(2)O(2) induced vasorelaxation and catalase blunted ACh-mediated vasorelaxation. In conclusion, Ca(2+)-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 H(2)O(2) production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Angiotensin II
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Aorta / metabolism
  • Arteries / drug effects
  • Arteries / enzymology
  • Arteries / physiopathology*
  • Blood Pressure
  • Cyclic GMP / metabolism
  • Drug Combinations
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Hypertension / chemically induced
  • Hypertension / enzymology
  • Hypertension / physiopathology*
  • Male
  • Mesenteric Arteries / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism*
  • Potassium Channels, Calcium-Activated / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Sodium Chloride
  • Vasodilation*
  • Vasodilator Agents / pharmacology


  • Antioxidants
  • Drug Combinations
  • Potassium Channels, Calcium-Activated
  • Vasodilator Agents
  • Angiotensin II
  • Nitric Oxide
  • Sodium Chloride
  • Hydrogen Peroxide
  • Nitric Oxide Synthase
  • Cyclic GMP
  • Acetylcholine