Different responses of arterioles and venules in rat gastric mucosal microcirculation to endothelin-1 and endothelin-3.
Responses of the microvessels in the basal part of the gastric mucosa of anesthetized rats to endothelin (ET)-1 and ET-3 were examined by intravital microscopy. The posterior wall of the stomach, which was incised along the greater curvature, was secured in an observation chamber and superfused with Tyrode's solution, and the microcirculation was observed through a window made by removing a limited area of smooth-muscle layers with the serosa and submucosal tissue. Topical application of the same ranges of ET-1 and ET-3 (0.1-10 microM, 20 microliters) to the window dose-dependently constricted collecting venules and venules downstream. The constriction was inhibited by BQ-123, an ETA receptor antagonist, but the equipotency of ET-1 and ET-3 did not support the presence of the ETA receptor (tentatively called ETR-m). Arterioles were constricted through ETR-m, particularly at higher doses (> 3 microM), but 1 microM ET-1 dilated the arterioles by generating prostaglandin through BQ-123-sensitive ET receptor (tentatively called ETR-e), as shown by the inhibition of dilatation by indomethacin. Furthermore, the dilatation component of the arteriolar smooth-muscle responses to ET-1 and ET-3 was elicited by BQ-123 and was inhibited by NG-monomethyl-L-arginine (L-NMMA), indicating the generation of nitric oxide. This dilating effect of the endothelins was mediated by the ETB receptor.
Ohno
T
T
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Katori
M
M
Majima
M
M
Hayashi
H
H
Saigenji
K
K
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019332:Endothelin-1; D019334:Endothelin-3; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D019323:omega-N-Methylarginine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)