Vasodilator mRNA levels are increased in the livers of portal hypertensive NO-synthase 3-deficient mice.
OBJECTIVE
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.
Biecker
E
E
Department of Clinical Pharmacology, University of Berne, Berne, Switzerland. Erwin.Biecker1@epost.de
Sägesser
H
H
Reichen
J
J
D053607:Adrenomedullin; D000818:Animals; D001652:Bile Ducts / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D006975:Hypertension, Portal / Q000201:enzymology* / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014665:Vasodilator Agents / Q000378:metabolism*
D010455:Peptides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D014665:Vasodilator Agents; D053607:Adrenomedullin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse