Mesenteric hyporesponsiveness in cirrhotic rats with ascites: Role of cGMP and K+ channels

N. M. Atucha, M. C. Ortiz, L. A. Fortepiani, F. J.A. Nadal, C. Martinez-Prieto, J. Garcia-Estan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 N(G)-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.

Original languageEnglish (US)
Pages (from-to)455-460
Number of pages6
JournalClinical science
Volume99
Issue number5
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Isolated and perfused mesentery
  • Liver cirrhosis
  • Methoxamine
  • Nitric oxide
  • Portal hypertension
  • Splanchnic circulation

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Atucha, N. M., Ortiz, M. C., Fortepiani, L. A., Nadal, F. J. A., Martinez-Prieto, C., & Garcia-Estan, J. (2000). Mesenteric hyporesponsiveness in cirrhotic rats with ascites: Role of cGMP and K+ channels. Clinical science, 99(5), 455-460. https://doi.org/10.1042/cs0990455