Linked Life Data

20444882

Source:http://linkedlifedata.com/resource/pubmed/id/20444882

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-7-19
pubmed:abstractText
Acute inhibition of nitric-oxide synthase (NOS) unmasks the release of endothelium-derived contracting factors (EDCFs). The present study investigated whether chronic inhibition of NOS modulates endothelium-dependent contractions. Eighteen-week-old male Sprague-Dawley rats were treated by daily gavage for 6 weeks with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg) or vehicle (distilled water; 1 ml/kg). Chronic treatment with L-NAME increased arterial blood pressure. Isometric tension was measured in aortic rings with or without endothelium. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore 5-(methylamino)-2-[(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)-ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187) were reduced in preparations from L-NAME-treated rats. The reduction in relaxation to A23187 was partially reversed by L-arginine (1 mM). In quiescent aortic rings, A23187 caused contractions in the presence of L-NAME and intact endothelium. The A23187-induced contractions were greater in rings from the L-NAME-treated rats than in those from the control group. These contractions were abolished by the cyclooxygenase (COX)-2 inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide (NS-398) and the thromboxane-prostanoid (TP) receptor antagonist 3-((6R)-6-{[(4-chlorophenyl)sulfonyl]amido}-2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)propanoate (S18886), but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560). Chronic L-NAME treatment reduced the level of nitric oxide in the plasma but increased COX activity in the aortic rings. Western blotting and immunohistochemical staining showed that endothelial NOS expression was reduced in the aortae of the chronic L-NAME-treated group. COX-1 expression was augmented slightly, whereas COX-2 expression was up-regulated markedly. The TP receptor expression was comparable with control. These experiments demonstrate that chronic NOS inhibition increases endothelium-dependent contractions of the rat aorta by inducing COX-2 expression and augmenting the production of EDCF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
334
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
373-80
pubmed:meshHeading
pubmed-meshheading:20444882-6-Ketoprostaglandin F1 alpha, pubmed-meshheading:20444882-Animals, pubmed-meshheading:20444882-Aorta, Thoracic, pubmed-meshheading:20444882-Cyclooxygenase 1, pubmed-meshheading:20444882-Cyclooxygenase 2, pubmed-meshheading:20444882-Cyclooxygenase Inhibitors, pubmed-meshheading:20444882-Dinoprost, pubmed-meshheading:20444882-Endothelium, Vascular, pubmed-meshheading:20444882-Isometric Contraction, pubmed-meshheading:20444882-Male, pubmed-meshheading:20444882-Muscle, Smooth, Vascular, pubmed-meshheading:20444882-Muscle Relaxation, pubmed-meshheading:20444882-NG-Nitroarginine Methyl Ester, pubmed-meshheading:20444882-Nitric Oxide Synthase, pubmed-meshheading:20444882-Nitric Oxide Synthase Type III, pubmed-meshheading:20444882-Rats, pubmed-meshheading:20444882-Rats, Sprague-Dawley, pubmed-meshheading:20444882-Thromboxane B2, pubmed-meshheading:20444882-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Chronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2.
pubmed:affiliation
Department of Pharmacology and Pharmacy, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong. rykman@hku.hk.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't