Department of Clinical Pharmacology, University of Berne, Murtenstrasse 35, 3010 Berne, Switzerland (E. Biecker, H. Sägesser, J. Reichen).
Vasodilator mRNA levels are increased in the livers of portal hypertensive NO-synthase 3-deficient mice
Article first published online: 13 APR 2004
European Journal of Clinical Investigation
Volume 34, Issue 4, pages 283–289, April 2004
How to Cite
Biecker, E., Sägesser, H. and Reichen, J. (2004), Vasodilator mRNA levels are increased in the livers of portal hypertensive NO-synthase 3-deficient mice. European Journal of Clinical Investigation, 34: 283–289. doi: 10.1111/j.1365-2362.2004.01331.x
- Issue published online: 13 APR 2004
- Article first published online: 13 APR 2004
- Received 15 December 2003; accepted 9 February 2004
- Bile duct ligation;
- liver diseases;
- nitric oxide synthase;
- nitric oxide;
- quantitative PCR;
Background/aims Nitric oxide synthase (NOS) 3-deficient (NOS-3 KO) mice have an increased systemic arterial pressure but develop portal hypertension to the same extent as wildtype (WT) mice. We hypothesized that other vasodilators in the portal circulation compensate for the lack in NOS-3 activity. We used quantitative PCR as a screening method to identify mediators that possibly compensate for NOS-3 in NOS-3 KO mice.
Methods Mean arterial pressure (MAP) and portal venous pressure (PVP) were measured in the anaesthetized animal. mRNA levels in whole liver tissue were determined by quantitative RT-PCR.
Results NOS-3 KO mice had a significantly higher mean arterial pressure than WT mice, but portal venous pressure did not differ. Bile duct ligation (BDL) induced a drop in MAP and a rise in PVP in both groups. Bile duct ligation induced a significant increase in mRNA levels of the cannabinoid receptor (CB)-1, adrenomedullin and NOS-2 in the liver of NOS-3 KO and WT mice. Nitric oxide synthase-1 and NOS-3 mRNA levels were elevated in BDL WT mice compared with sham-operated WT mice. Higher mRNA levels of CB-1, NOS-1 and the adrenomedullin receptor were found in sham-operated NOS-3 KO mice compared with sham-operated WT mice.
Conclusions We used quantitative PCR as a screening method to identify vasodilative mediators that might be involved in the compensation for the lack of NOS-3 activity in NOS-3 KO mice. Elevated mRNA levels in sham-operated NOS-3 KO mice compared with sham-operated WT mice were demonstrated for CB-1, NOS-1 and the adrenomedullin receptor.