Nitric oxide-mediated beta 2-adrenoceptor relaxation is impaired in mesenteric veins from portal-hypertensive rats.
OBJECTIVE
beta-Adrenergic relaxation seems to be mediated by nitric oxide. The aim of this study was to evaluate changes induced by portal hypertension in beta 2-adrenergic vasorelaxation.


METHODS
Isolated rat mesenteric veins were relaxed by salbutamol, and nerve-mediated vasocontractions were induced by electrical field stimulation. Responses were evaluated in the presence of NG-nitro-L-arginine methyl ester (L-NAME) or tetrodotoxin. Immunocytochemical techniques were used for localization of neuronal NO synthase.


RESULTS
Salbutamol-induced relaxations were decreased in rings from portal-hypertensive animals. L-NAME reduced these relaxations, but its effects were more pronounced in sham-operated rats. Tetrodotoxin decreased the effect of salbutamol only in rings from sham-operated animals. Combination of L-NAME and tetrodotoxin did not exert a greater effect than either of these agents alone. Veins from portal-hypertensive animals were more sensitive to S-nitroso-N-acetyl penicillamine. L-NAME increased vasocontractions by electrical stimulation only in rings from sham-operated rats. Veins from portal-hypertensive animals exhibited a specific degeneration of NO-containing nerve endings.


CONCLUSIONS
beta 2-Adrenergic relaxation is impaired in mesenteric veins from portal-hypertensive rats, possibly as a result of a defective neuronal release of NO.
Martínez-Cuesta
M A
MA
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Moreno
L
L
Piqué
J M
JM
Bosch
J
J
Rodrigo
J
J
Esplugues
J V
JV
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006975:Hypertension, Portal / Q000503:physiopathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010208:Papaverine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013779:Tetrodotoxin; D026423:S-Nitroso-N-Acetylpenicillamine; D010208:Papaverine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D000420:Albuterol; D019331:NG-Nitroarginine Methyl Ester