title: Heterogeneity in vascular smooth muscle responsiveness to angiotensin II. Role of endothelin.
abstract: We compared the role of endothelium and of endothelin in mediating the vasoconstrictor responses to angiotensin II (Ang II) in three vascular smooth muscle preparations--aorta, mesenteric artery, and tail artery--isolated from adult male Sprague-Dawley rats. The vasoconstrictor potency for Ang II in blood vessels with endothelium varied in the following rank order: aorta > mesenteric artery > tail artery. Although the maximal tension responses to Ang II were similar for mesenteric and tail arteries, it was significantly lower in aorta. Endothelium removal led to a leftward shift in the concentration-response curves to Ang II in the aorta but a rightward shift in the mesenteric artery. Strikingly, Ang II failed to evoke tension responses in tail artery in the absence of endothelium. The endothelin-A (ETA)-selective antagonist BQ-123 blocked the responses to Ang II in a noncompetitive manner, with partial and complete attenuation of responses in the endothelium-intact mesenteric and tail artery preparations, respectively. In contrast, BQ-123 did not affect the responses to Ang II in the aorta. BQ-123 also failed to affect the responses to Ang II in endothelium-denuded mesenteric artery rings. The Ang II type 1 (AT1) receptor-selective antagonist losartan competitively blocked the responses to Ang II in the three tissues (pA2, 8.3 to 8.7) when endothelium was present. These data suggest that there are endothelium-dependent regional variations in vascular tissue sensitivity to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: J R
authors.initials: JR
authors.lastname: McNeill
authors.forename: T W
authors.initials: TW
authors.lastname: Wilson
authors.forename: V
authors.initials: V
authors.lastname: Gopalakrishnan
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta; D001158:Arteries; D001713:Biphenyl Compounds / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007093:Imidazoles; D010456:Peptides, Cyclic; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)