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A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats.
J Hepatol. 2003 Dec; 39(6):940-6.JH

Abstract

BACKGROUND/AIMS

A decreased intra-hepatic nitric oxide (NO) production participates on the pathogenesis of portal hypertension in cirrhosis. We tested the hemodynamic effects of a liver-specific NO donor (NCX-1000) derived from ursodeoxycholic acid in portal hypertensive cirrhotic rats.

METHODS

After a 14-day treatment with ursodeoxycholic acid or NCX-1000 by gavage, ascitic cirrhotic rats (CCl4-induced) were used in two studies: (1) in vivo mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery (SMA) blood flow measurements before and during progressive blood volume expansion (blood infusion); and (2) in situ liver perfusion to obtain dose/response curves to methoxamine (alpha1-adrenergic agonist) and flow/pressure curves.

RESULTS

Basal heart rate, MAP, and PP were similar in both groups. During blood infusion, similar MAP and SMA flow increases were observed in both groups; however, PP increase observed in control rats was blunted in NCX-1000 treated rats (P=0.015). In liver perfusions, flow/pressure curves were similar in both groups; however, NCX-1000-treated livers showed a lower response to methoxamine (P=0.016). cGMP concentration in NCX-1000-treated livers was higher (P=0.015) than in controls.

CONCLUSIONS

Treatment with a liver-specific NO donor improves the portal system adaptability to portal blood flow increase and ameliorates the intra-hepatic response to methoxamine in cirrhotic rats.

Authors+Show Affiliations

Loureiro-Silva MR
Hepatic Hemodynamic Laboratory, Digestive Diseases Section/111H, VA Medical Center, 950 Campbell Avenue, West Haven, CT 06516, USA.
Cadelina GW
No affiliation info available
Iwakiri Y
No affiliation info available
Groszmann RJ
No affiliation info available

MeSH

AnimalsDrug InteractionsHypertension, PortalLiver CirculationLiver CirrhosisMaleMesenteric Artery, SuperiorMethoxamineNitratesNitric Oxide DonorsPortal VeinRatsRats, Sprague-DawleyUrsodeoxycholic AcidVascular ResistanceVasoconstrictor Agents

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

14642609

Citation

Loureiro-Silva, Mauricio R., et al. "A Liver-specific Nitric Oxide Donor Improves the Intra-hepatic Vascular Response to Both Portal Blood Flow Increase and Methoxamine in Cirrhotic Rats." Journal of Hepatology, vol. 39, no. 6, 2003, pp. 940-6.
Loureiro-Silva MR, Cadelina GW, Iwakiri Y, et al. A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. J Hepatol. 2003;39(6):940-6.
Loureiro-Silva, M. R., Cadelina, G. W., Iwakiri, Y., & Groszmann, R. J. (2003). A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. Journal of Hepatology, 39(6), 940-6.
Loureiro-Silva MR, et al. A Liver-specific Nitric Oxide Donor Improves the Intra-hepatic Vascular Response to Both Portal Blood Flow Increase and Methoxamine in Cirrhotic Rats. J Hepatol. 2003;39(6):940-6. PubMed PMID: 14642609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. AU - Loureiro-Silva,Mauricio R, AU - Cadelina,Gregory W, AU - Iwakiri,Yasuko, AU - Groszmann,Roberto J, PY - 2003/12/4/pubmed PY - 2004/8/4/medline PY - 2003/12/4/entrez SP - 940 EP - 6 JF - Journal of hepatology JO - J Hepatol VL - 39 IS - 6 N2 - BACKGROUND/AIMS: A decreased intra-hepatic nitric oxide (NO) production participates on the pathogenesis of portal hypertension in cirrhosis. We tested the hemodynamic effects of a liver-specific NO donor (NCX-1000) derived from ursodeoxycholic acid in portal hypertensive cirrhotic rats. METHODS: After a 14-day treatment with ursodeoxycholic acid or NCX-1000 by gavage, ascitic cirrhotic rats (CCl4-induced) were used in two studies: (1) in vivo mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery (SMA) blood flow measurements before and during progressive blood volume expansion (blood infusion); and (2) in situ liver perfusion to obtain dose/response curves to methoxamine (alpha1-adrenergic agonist) and flow/pressure curves. RESULTS: Basal heart rate, MAP, and PP were similar in both groups. During blood infusion, similar MAP and SMA flow increases were observed in both groups; however, PP increase observed in control rats was blunted in NCX-1000 treated rats (P=0.015). In liver perfusions, flow/pressure curves were similar in both groups; however, NCX-1000-treated livers showed a lower response to methoxamine (P=0.016). cGMP concentration in NCX-1000-treated livers was higher (P=0.015) than in controls. CONCLUSIONS: Treatment with a liver-specific NO donor improves the portal system adaptability to portal blood flow increase and ameliorates the intra-hepatic response to methoxamine in cirrhotic rats. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/14642609/A_liver_specific_nitric_oxide_donor_improves_the_intra_hepatic_vascular_response_to_both_portal_blood_flow_increase_and_methoxamine_in_cirrhotic_rats_ DB - PRIME DP - Unbound Medicine ER -