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Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats.
J Hepatol. 1999 Aug; 31(2):300-5.JH

Abstract

BACKGROUND/AIMS

Increased intrahepatic vascular tone can be pharmacologically manipulated in isolated cirrhotic livers. Intrahepatic endothelial dysfunction may lead to a decreased production of the potent endogenous vasodilator nitric oxide in cirrhotic livers. The aims of the study were to determine whether portal pressure can be lowered in vivo by injecting nitric oxide donors glyceryl trinitrate or nitroprusside directly in the portal vein and whether this is related to a decrease in intrahepatic resistance.

METHODS

In anaesthetised CCl4 cirrhotic rats, intraportal doses of glyceryl trinitrate 0.5, 1 or 5 microg/kg/ min or nitroprusside 1, 5 or 10 microg/kg/min did not decrease portal pressure but only arterial pressure. Systemic and splanchnic haemodynamics were measured before and during 15 min intraportal infusion of glyceryl trinitrate 10 microg/kg/min or nitroprusside 20 microg/kg/min.

RESULTS

Glyceryl trinitrate decreased portal pressure from 14.0+/-1.1 to 11.8+/-1.4 mm Hg, splanchnic perfusion pressure from 102+/-10 to 74+/-5 mm Hg and portal sinusoidal flow from 2.11+/-0.38 to 1.70+/-0.35 ml/min/g liver (all p<0.05). Nitroprusside did not decrease portal pressure significantly but led to a reduction of the splanchnic perfusion pressure (104+/-9 to 66+/-7 mm Hg) and the portal sinusoidal flow (2.39+/-0.50 to 1.77+/-0.31 ml/min/g liver; all p<0.05). Portal sinusoidal resistance was not altered by either drug.

CONCLUSIONS

Intraportal infusion of nitric oxide donors decreased arterial pressure more than portal pressure. Portal sinusoidal resistance remained unaffected, but the liver parenchyma became less perfused with high doses. The systemic effects of nitric oxide donating drugs prevailed.

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Authors+Show Affiliations

Van de Casteele M
Department of Clinical Pharmacology, University of Berne, Switzerland.
Hösli M
No affiliation info available
Sägesser H
No affiliation info available
Reichen J
No affiliation info available

MeSH

AnimalsBlood PressureHypertension, PortalInfusions, IntravenousLiver CirculationLiver Cirrhosis, ExperimentalMaleNitric OxideNitric Oxide DonorsNitroglycerinNitroprussidePortal VeinRatsRats, Sprague-DawleySplanchnic CirculationVascular ResistanceVasodilator Agents

Pub Type(s)

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

Language

eng

PubMed ID

10453944

Citation

Van de Casteele, M, et al. "Intraportal Administration of Glyceryl Trinitrate or Nitroprusside Exerts More Systemic Than Intrahepatic Effects in Anaesthetised Cirrhotic Rats." Journal of Hepatology, vol. 31, no. 2, 1999, pp. 300-5.
Van de Casteele M, Hösli M, Sägesser H, et al. Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats. J Hepatol. 1999;31(2):300-5.
Van de Casteele, M., Hösli, M., Sägesser, H., & Reichen, J. (1999). Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats. Journal of Hepatology, 31(2), 300-5.
Van de Casteele M, et al. Intraportal Administration of Glyceryl Trinitrate or Nitroprusside Exerts More Systemic Than Intrahepatic Effects in Anaesthetised Cirrhotic Rats. J Hepatol. 1999;31(2):300-5. PubMed PMID: 10453944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats. AU - Van de Casteele,M, AU - Hösli,M, AU - Sägesser,H, AU - Reichen,J, PY - 1999/8/24/pubmed PY - 1999/8/24/medline PY - 1999/8/24/entrez SP - 300 EP - 5 JF - Journal of hepatology JO - J Hepatol VL - 31 IS - 2 N2 - BACKGROUND/AIMS: Increased intrahepatic vascular tone can be pharmacologically manipulated in isolated cirrhotic livers. Intrahepatic endothelial dysfunction may lead to a decreased production of the potent endogenous vasodilator nitric oxide in cirrhotic livers. The aims of the study were to determine whether portal pressure can be lowered in vivo by injecting nitric oxide donors glyceryl trinitrate or nitroprusside directly in the portal vein and whether this is related to a decrease in intrahepatic resistance. METHODS: In anaesthetised CCl4 cirrhotic rats, intraportal doses of glyceryl trinitrate 0.5, 1 or 5 microg/kg/ min or nitroprusside 1, 5 or 10 microg/kg/min did not decrease portal pressure but only arterial pressure. Systemic and splanchnic haemodynamics were measured before and during 15 min intraportal infusion of glyceryl trinitrate 10 microg/kg/min or nitroprusside 20 microg/kg/min. RESULTS: Glyceryl trinitrate decreased portal pressure from 14.0+/-1.1 to 11.8+/-1.4 mm Hg, splanchnic perfusion pressure from 102+/-10 to 74+/-5 mm Hg and portal sinusoidal flow from 2.11+/-0.38 to 1.70+/-0.35 ml/min/g liver (all p<0.05). Nitroprusside did not decrease portal pressure significantly but led to a reduction of the splanchnic perfusion pressure (104+/-9 to 66+/-7 mm Hg) and the portal sinusoidal flow (2.39+/-0.50 to 1.77+/-0.31 ml/min/g liver; all p<0.05). Portal sinusoidal resistance was not altered by either drug. CONCLUSIONS: Intraportal infusion of nitric oxide donors decreased arterial pressure more than portal pressure. Portal sinusoidal resistance remained unaffected, but the liver parenchyma became less perfused with high doses. The systemic effects of nitric oxide donating drugs prevailed. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/10453944/Intraportal_administration_of_glyceryl_trinitrate_or_nitroprusside_exerts_more_systemic_than_intrahepatic_effects_in_anaesthetised_cirrhotic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168827899802281 DB - PRIME DP - Unbound Medicine ER -