The mechanisms that mediate hyporesponsiveness to vasoconstrictors in liver cirrhosis are not completely established. In the present study we have explored the role of NO and potassium channels by studying the pressor response to methoxamine in rats with carbon tetrachloride-induced cirrhosis with ascites. Experiments were performed in the isolated and perfused mesenteric arterial bed of control rats and of cirrhotic rats with ascites. Pressor responses to methoxamine, an α-adrenergic agonist, were analysed under basal conditions, after inhibition of guanylate cyclase with Methylene Blue (MB; 10 µM), after inhibition of NO synthesis with NG-nitro-L-arginine (L-NNA; 100 µM) and after blockade of potassium channels with tetraethylammonium (TEA; 3 mM). Compared with those from controls, preparations from cirrhotic rats showed a lower pressor response to methoxamine (maximum: controls, 114.4±6.8 mmHg; cirrhotic rats, 74.7±7.3 mmHg). Pretreatment with MB or L-NNA increased the responses in both groups, but without correcting the lower than normal response of the cirrhotic rats. Pretreatment with TEA alone did not modify the responses as compared with the untreated groups. Pretreatment with TEA plus MB or TEA plus L-NNA also potentiated the responses, and the responses of the cirrhotic animals were greater than those of the groups treated with MB or L-NNA alone. However, no treatment completely normalized the lower response of the mesenteries from cirrhotic animals, suggesting that factors other than NO and potassium channels also participate, although to a lesser degree, in the lower pressor response of the mesenteric arterial bed of animals with cirrhosis. These results confirm that NO and potassium channels are important mediators of the lower vascular pressor response of the mesenteric bed of cirrhotic rats with ascites. This effect seems to be mediated by the NO-dependent formation of cGMP and by the NO-dependent and -independent activation of potassium channels.
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October 27 2000
Mesenteric hyporesponsiveness in cirrhotic rats with ascites: role of cGMP and K+ channels
Noemí M. ATUCHA;
1Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain
Correspondence: Dr Noemí M. Atucha (e-mail [email protected]).
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M. Clara ORTÍZ;
M. Clara ORTÍZ
1Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain
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Lourdes A. FORTEPIANI;
Lourdes A. FORTEPIANI
1Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain
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Francisco Javier A. NADAL;
Francisco Javier A. NADAL
1Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain
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Concepción MARTÍNEZ-PRIETO;
Concepción MARTÍNEZ-PRIETO
1Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain
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Joaquín GARCÍA-ESTAÑ
Joaquín GARCÍA-ESTAÑ
1Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain
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Publisher: Portland Press Ltd
Received:
March 10 2000
Revision Received:
June 27 2000
Accepted:
July 26 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (5): 455–460.
Article history
Received:
March 10 2000
Revision Received:
June 27 2000
Accepted:
July 26 2000
Citation
Noemí M. ATUCHA, M. Clara ORTÍZ, Lourdes A. FORTEPIANI, Francisco Javier A. NADAL, Concepción MARTÍNEZ-PRIETO, Joaquín GARCÍA-ESTAÑ; Mesenteric hyporesponsiveness in cirrhotic rats with ascites: role of cGMP and K+ channels. Clin Sci (Lond) 1 November 2000; 99 (5): 455–460. doi: https://doi.org/10.1042/cs0990455
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