title: The influence of the wall tension on the contractile responses of arteries.
abstract: The present study aimed at determining the influence of tension on the responses of arterial smooth muscle to noradrenaline, phenylephrine and angiotensin II. Concentration-response curves to these agonists were obtained in the rat aorta, at two levels of tension: 3 g (29.4 mN) and 0.5 g (4.9 mN). The results obtained show that the maximal responses to the agonists used (in percent of the maximal response to noradrenaline) were significantly larger (P < 0.05) at 3 g than at 0.5 g: 113% versus 66%, respectively, for noradrenaline; 95% versus 59%, respectively, for phenylephrine; 60% versus 24%, respectively, for angiotensin II. In the presence of gadolinium (100 mumol/L)--a mechanogated ion channel blocker--the responses to noradrenaline at 3 g were still significantly larger than responses at 0.5 g: 103% versus 67%, respectively. The compound H-7 (20 mumol/L)--a protein kinase C inhibitor--caused a marked decrease in the maximal responses to noradrenaline at both levels of tension, the responses being reduced to 44% at 3 g and to 20% at 0.5 g. Isradipine (1 mumol/L)--a calcium channel blocker--caused a slight decrease in the responses to noradrenaline at both levels of tension, the responses being reduced to 86% (3 g) and to 50% (0.5 g). In endothelium-free arterial rings, the responses to noradrenaline at 3 g and 0.5 g were also significantly different: 118% versus 80%, respectively. It is concluded that the tension of the arterial wall is a major factor influencing the effects of vasoconstrictor agents; however the mechanisms underlying this supersensitivity at higher tension remain unknown.
authors.affiliation: Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
authors.forename: J P
authors.initials: JP
authors.lastname: Nunes
authors.forename: S
authors.initials: S
authors.lastname: Guimarães
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001158:Arteries / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D010656:Phenylephrine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005682:Gadolinium; D011493:Protein Kinase C; D009638:Norepinephrine; D017275:Isradipine