title: Reduced capacitative calcium entry in the mesenteric vascular bed of bile duct-ligated rats.
abstract: In this work, we analyzed the interaction of nitric oxide (NO) with some of the mechanisms known to regulate intracellular calcium levels in order to gain insight into the mechanisms responsible for the reduced vascular pressor response to vasoconstrictors observed in an experimental model of liver cirrhosis. Specifically, we hypothesized that the entry of calcium through capacitative channels is defective in this model. The experiments were performed with isolated, Krebs-perfused and de-endothelialized mesenteric arterial bed of rats with bile duct ligation (4 weeks) and their controls. Pretreatment with thapsigargin to inhibit calcium uptake into sarcoplasmic reticulum potentiated the pressor responses to methoxamine, but the response of the cirrhotic vessels was significantly lower than that of the controls. Under the same conditions, perfusion of the mesenteries with zero calcium-Krebs resulted in lower pressor responses to methoxamine, especially in the mesenteries of the bile duct-ligated rats. To specifically analyze the entry of calcium through store-operated calcium channels, the pressor response to the addition of calcium was studied in mesenteries perfused with zero calcium-Krebs and in the presence of thapsigargin. Again, the response of the cirrhotic mesenteric beds was significantly lower than that of the control vessels. Under all these experimental conditions, the differences between control and cirrhotic responses were abolished by pretreatment with the NO synthesis inhibitor N(w)-nitro-L-arginine (NNA). These results indicate that, in the mesenteric bed of bile duct-ligated rats, an excess of nitric oxide interferes with the release of calcium from thapsigargin-sensitive internal stores and also reduces the capacitative entry of calcium into vascular muscular cells induced by the depletion of calcium from internal stores. This mechanism may have an important role in the reduced pressor response observed in the mesenteric vascular bed in cirrhosis.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, 30100 Murcia, Spain.
authors.forename: Noemí M
authors.initials: NM
authors.lastname: Atucha
authors.forename: F Javier A
authors.initials: FJ
authors.lastname: Nadal
authors.forename: Antonia
authors.initials: A
authors.lastname: Alcaraz
authors.forename: David
authors.initials: D
authors.lastname: Iyú
authors.forename: M Clara
authors.initials: MC
authors.lastname: Ortiz
authors.forename: Joaquín
authors.initials: J
authors.lastname: García-Estañ
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001652:Bile Ducts; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D008729:Methoxamine / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D008729:Methoxamine; D002118:Calcium