Effects of vasoactive substances on the pig isolated hepatic lymph vessels
Hashimoto, S.; Kawai, Y.; Ohhashi, T.
Journal of Pharmacology and Experimental Therapeutics 269(2): 482-488
1994
ISSN/ISBN: 0022-3565 PMID: 8182515 Document Number: 429076
The present study examined the responses of isolated pig hepatic lymph vessels to vasoactive substances, the classification of alpha adrenoceptors and the mode of action of acetylcholine (ACh) with special reference to the lymphatic endothelial cells. Contractions of the hepatic lymph vessels were induced by norepinephrine (NE), epinephrine, prostaglandin F-2alpha, histamine and 5-hydroxytryptamine in a dose-dependent manner. NE was the most potent vasoconstrictor agent. 5-bromo-6(2-imidazolin-2-ylamino)-quinoxaline, xylazine and clonidine also produced dose-dependent contractions. NE-induced contractions were inhibited significantly by yohimbine (10-8-10-6 M) but not by prazosin (10-8-10-6 M). Pretreatment with yohimbine (10-8-10-7 M) or rauwolscine (10-8-10-7 M) caused a parallel shift to the right of the dose-response curve for 5-bromo-6(2-imidazolin-2-ylamino)-quinoxaline. These results suggest that the NE-induced contraction in pig hepatic lymph vessels seems to be mediated mainly through stimulation of alpha-2 adrenoceptors. ACh, isoproterenol, histamine, 5-hydroxytryptamine, ATP and adenosine caused dose-dependent relaxations in the hepatic lymph vessels precontracted by 5 times 10-6 M prostaglandin F-2alpha. ACh was the most potent vasorelaxant agent. Pretreatment with atropine (10-9-10-7 M) inhibited the ACh-induced relaxation in a competitive manner. Removal of endothelium caused a significant reduction of the ACh-induced relaxation. The ACh-induced relaxation was suppressed by pretreatment with N-omega-nitro-L-arginine methyl ester (3 times 10-5 M) and methylene blue (10-5 M) but was unaffected by aspirin (10-5 M). Additional treatment with L-arginine (10-3 M) in the presence of 3 times 10-5 M N-omega-nitro-L-arginine methyl ester reversed completely the N-omega-nitro-L-arginine methyl ester-induced reduction of the relaxation. These results suggest that ACh causes the release of nitric oxide or its related compounds from the endothelial cells, which results in the relaxation of the hepatic lymph vessels via the accumulation of cellular guanosine 3',5'-cyclic monophosphate.