Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension.
OBJECTIVE
In portal hypertension, the mechanisms responsible for nitric oxide (NO) overproduction and vasodilation have not yet been clearly identified. One hypothesis is that NO synthase (NOS) 3 is overactivated because of shear stress in endothelial cells caused by hyperkinetic circulation. The aim of this study was to evaluate aortic NOS3 after a reduction of blood flow by long-time beta-adrenoceptor antagonist administration.


METHODS
Propranolol or atenolol was administered by gavage in portal vein-stenosed and sham-operated rats. The vascular reactivity of thoracic aortic rings to phenylephrine, total aortic NOS activity, and aortic NOS3 messenger RNA and protein expressions were studied.


RESULTS
After propranolol or atenolol administration, the aortic hyporesponse returned to normal in portal vein-stenosed rats. Total aortic NOS activity was higher in portal vein-stenosed aortas and significantly decreased after beta-blocker administration. Aortic NOS3 expressions were more marked in portal vein-stenosed aortas than in controls, but NOS3 expressions were reduced after propranolol administration.


CONCLUSIONS
In portal hypertension, aortic NOS3 activity and expressions are enhanced but return to normal after beta-blocker administration. These results suggest that in portal hypertension, increased shear stress, related to high blood flow, induces enhanced aortic NOS3.
Pateron
D
D
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM Unité 481, Hôpital Beaujon, Clichy, France.
Tazi
K A
KA
Sogni
P
P
Heller
J
J
Chagneau
C
C
Poirel
O
O
Philippe
M
M
Moreau
R
R
Lebrec
D
D
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000201:enzymology*; D001262:Atenolol / Q000494:pharmacology; D003251:Constriction, Pathologic; D006975:Hypertension, Portal / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D011169:Portal Vein / Q000503:physiopathology; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D012333:RNA, Messenger; D014665:Vasodilator Agents; D001262:Atenolol; D011433:Propranolol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat