In vitro hyporeactivity to methoxamine in portal hypertensive rats: reversal by nitric oxide blockade.
The endothelial cell plays an important role in the local control of vascular smooth muscle tone. Portal hypertension is accompanied by systemic vasodilatation and a decreased response to vasoconstrictors, changes especially evident in the superior mesenteric arterial bed. To evaluate a possible effect of the locally released endothelium-derived relaxing factor nitric oxide (NO), we tested the effect of NO blockade in in vitro perfused superior mesenteric arterial beds of normal (sham) and portal hypertensive (PVL) rats, induced by partial portal vein ligation. A significant (n = 7/group; P = 0.02) hyporeactivity to the vasoconstrictive properties of the alpha-adrenoceptor agonist methoxamine (3 x 10(-6) to 3 x 10(-4) M) was prevented by blocking NO formation in PVL compared with sham rats, using the stereospecific biosynthesis antagonist N omega-nitro-L-arginine (10(-4) M, n = 7/group; NS for all methoxamine concentrations tested). This effect was reversed by the NO precursor L-arginine (10(-3) M, n = 5/group). In conclusion, these in vitro results in mesenteric vessels demonstrate that 1) portal hypertension is accompanied by a hyporeactivity to the vasopressor methoxamine and 2) locally released NO in this preparation is responsible for the decreased vasoconstrictive response.
Sieber
C C
CC
Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut.
Groszmann
R J
RJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006975:Hypertension, Portal / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008729:Methoxamine / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D008729:Methoxamine; D000109:Acetylcholine