Pharmacology of portal-systemic collaterals in portal hypertensive rats: role of endothelium.
The portal-systemic collateral circulation of portal hypertensive rats was studied. The collaterals were perfused through the mesenteric vein with Krebs solution, which was allowed to escape through the jugular veins. The portal-collateral resistance can be quantitated from slopes of the pressure-flow relationships. In collaterals perfused at constant flow, both norepinephrine (NE) and 5-hydroxytryptamine (5-HT) increased the perfusion pressure. Phentolamine caused surmountable antagonism of the constrictor effects of NE, suggesting an involvement of alpha-adrenoceptors. The effects of 5-HT were competitively blocked by the 5-HT2 receptor-selective antagonist ICI 169,369. Isoproterenol dilated NE-preconstricted collaterals. The effect of isoproterenol was blocked by propranolol, demonstrating that the effect was mediated by beta-adrenoceptors. Acetylcholine (ACh) dilated NE-preconstricted collaterals. The dilatation effect of ACh was absent in collaterals in which the endothelium was removed. The competitive inhibitor of the nitric oxide synthase, N omega-nitro-L-arginine (L-NNA), increased collateral resistance and prevented the ACh-induced dilatation of the collaterals. The constrictor response to L-NNA and the blockade of the ACh-induced relaxation by both L-NNA and removal of endothelium are consistent with an involvement of nitric oxide. This experimental model can thus be used to explore the pathophysiological and the pharmacological properties of the collateral venous bed in portal hypertensive states.
Mosca
P
P
Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516.
Lee
F Y
FY
Kaumann
A J
AJ
Groszmann
R J
RJ
D000818:Animals; D001794:Blood Pressure; D003097:Collateral Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D011168:Portal System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents