L-NAME augments PAF-induced venoconstriction in isolated perfused livers of rat and guinea pig, but not mouse.
Platelet-activating factor (PAF), one of vasoconstrictive lipid mediators, is involved in systemic anaphylaxis. On the other hand, nitric oxide (NO) is known to attenuate anaphylactic venoconstriction of the pre-sinusoids in isolated guinea pig and rat livers. However, it is not known whether NO attenuates PAF-induced hepatic venoconstriction. We therefore determined the effects of L-NAME, a NO synthase inhibitor, on PAF-induced venoconstriction in blood- and constant flow-perfused isolated livers of mice, rats and guinea pigs. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. PAF (0.01-1 microM) concentration-dependently caused predominant pre-sinusoidal constriction in all livers of three species studied. The guinea pig livers were the most sensitive to PAF, while the mouse livers were the weakest in responsiveness. L-NAME pretreatment selectively increased the basal Rpre in all of three species. L-NAME also significantly augmented the PAF-induced increases in Rpre, but not in Rpost, in rat and guinea pig livers. This augmentation was stronger in rat livers than in guinea pig livers at the high concentration of 0.1 microM PAF. However, L-NAME did not augment PAF-induced venoconstriction in mouse livers. In conclusion, in rat and guinea pig livers, NO may be released selectively from the pre-sinusoids in response to PAF, and then attenuate the PAF-induced pre-sinusoidal constriction. In mouse liver, PAF-induced venoconstriction is weak and not modulated by NO.
Cui
Sen
S
Department of Physiology, Kanazawa Medical University, Uchinada 920-0293, Japan.
Shibamoto
Toshishige
T
Zhao
Zhansheng
Z
Takano
Hiromichi
H
Kurata
Yasutaka
Y
D000818:Animals; D006168:Guinea Pigs; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism / Q000494:pharmacology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D010972:Platelet Activating Factor; D019331:NG-Nitroarginine Methyl Ester