Role of endothelin-1 in congestive gastropathy in portal hypertensive rats.
BACKGROUND
The aim of this study was to determine the role of endothelin (ET)-1 in portal hypertensive gastropathy (PHG) under portal hypertension, in order to investigate whether the ET(A/B) receptor inhibitor improves the permeability of gastric mucosal microvessels in PHG.


RESULTS
Portal hypertensive rats (PVL) and sham-operated rats (CTR) were prepared and then the concentration of plasma ET-1 was measured and the vasopressor response to ET-1 was compared between the two groups. The plasma ET-1 levels in PVL increased significantly compared with CTR; however, the vasopressor response to ET-1 in PVL decreased more than in CTR. Next, the portal venous pressure was measured in both CTR and PVL pretreated with or without a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), before the injection of ET-1. The portal venous pressure of PVL after receiving ET-1 and being pretreated with L-NAME significantly increased in comparison to the pressure of PVL treated with ET-1 alone (without L-NAME). Moreover, Evans-Blue was injected into each rat and the absorbancy of the gastric contents was measured. The absorbancy of Evans-Blue in PVL increased significantly compared with CTR; however, the absorbancy in PVL+ ET(A/B) receptor inhibitor (Ro47-0203) decreased significantly more than in PVL.


CONCLUSIONS
This study showed that ET-1 is a potent vasoconstrictive substance that also has a transitory vasodilative response through NO induced by ET-1 in portal hypertension. In addition, it was found that the vascular permeability of the gastric mucosa increased in portal hypertension and that Ro47-0203 inhibited the hyper-permeability. Accordingly, ET-1 may, thus, play an important role in the development of PHG through NO induced by ET-1. Ro47-0203 may, therefore, be a useful substance for improving PHG in portal hypertension.
Migoh
S
S
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hashizume
M
M
Tsugawa
K
K
Tanoue
K
K
Sugimachi
K
K
D000818:Animals; D000077300:Bosentan; D002199:Capillary Permeability; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply*; D006975:Hypertension, Portal / Q000150:complications*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000209:etiology*; D013449:Sulfonamides / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D009569:Nitric Oxide; D000077300:Bosentan; D019331:NG-Nitroarginine Methyl Ester