Document Detail


Novel nitric oxide synthase--dependent mechanism of vasorelaxation in small arteries from hypertensive rats.
MedLine Citation:
PMID:  17309950     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kyu-Tae Kang; Jennifer C Sullivan; Jennifer M Sasser; John D Imig; Jennifer S Pollock
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-02-19
Journal Detail:
Title:  Hypertension     Volume:  49     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-22     Completed Date:  2007-04-05     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  893-901     Citation Subset:  IM    
Affiliation:
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Angiotensin II
Animals
Antioxidants / metabolism,  pharmacology
Aorta / metabolism
Arteries / drug effects,  enzymology,  physiopathology*
Blood Pressure
Cyclic GMP / metabolism
Drug Combinations
Hydrogen Peroxide / metabolism,  pharmacology
Hypertension / chemically induced,  enzymology,  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
Grant Support
ID/Acronym/Agency:
AG24616/AG/NIA NIH HHS; HL59699/HL/NHLBI NIH HHS; HL60653/HL/NHLBI NIH HHS; HL69999/HL/NHLBI NIH HHS; HL74167/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Drug Combinations; 0/Potassium Channels, Calcium-Activated; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 11128-99-7/Angiotensin II; 51-84-3/Acetylcholine; 7647-14-5/Sodium Chloride; 7665-99-8/Cyclic GMP; 7722-84-1/Hydrogen Peroxide; EC 1.14.13.39/Nitric Oxide Synthase

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