The influence of the wall tension on the contractile responses of arteries.
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.
Nunes
J P
JP
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Guimarães
S
S
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
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