S. Hashimoto et al., EFFECTS OF VASOACTIVE SUBSTANCES ON THE PIG ISOLATED HEPATIC LYMPH VESSELS, The Journal of pharmacology and experimental therapeutics, 269(2), 1994, pp. 482-488
The present study examined the responses of isolated pig hepatic lymph
vessels to vasoactive substances, the classification of alpha adrenoc
eptors and the mode of action of acetylcholine (ACh) with special refe
rence to the lymphatic endothelial cells. Contractions of the hepatic
lymph vessels were induced by norepinephrine (NE), epinephrine, prosta
glandin F-2 alpha histamine and 5-hydroxytryptamine in a dose-dependen
t manner. NE was the most potent vasoconstrictor agent. 5-bromo-6[2-im
idazolin-2-ylamino]-quinoxaline, xylazine and clonidine also produced
dose-dependent contractions. NE-induced contractions were inhibited si
gnificantly 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 rauwolsci
ne (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. Thes
e results suggest that the NE-induced contraction in pig hepatic lymph
vessels seems to be mediated mainly through stimulation of alpha-2 ad
renoceptors. ACh, isoproterenol, histamine, 5-hydroxytryptamine, ATP a
nd adenosine caused dose-dependent relaxations in the hepatic lymph ve
ssels precontracted by 5 x 10(-6) M prostaglandin F-2 alpha. ACh was t
he 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-ind
uced relaxation. The ACh-induced relaxation was suppressed by pretreat
ment with N omega-nitro-L-arginine methyl ester (3 x 10(-5) M) and met
hylene blue (10(-5) M) but was unaffected by aspirin (10(-5) M). Addit
ional treatment with L-arginine (10(-3) M) in the presence of 3 x 10(-
5)M Nw-nitro-L-arginine methyl ester reversed completely the Nw-nitro-
L-arginine methyl ester-induced reduction of the relaxation. These res
ults suggest that ACh causes the release of nitric oxide or its relate
d compounds from the endothelial cells, which results in the relaxatio
n of the hepatic lymph vessels via the accumulation of cellular guanos
ine 3',5'-cyclic monophosphate.