Mechanical stretch reveals different components of endothelial-mediated vascular tone in rat aortic strips

1 Since the role of mechanical stretches in vascular tone regulation is poo rly understood, we studied how stretch can influence endothelial tone. 2 Isometric contractions of isolated rat aortic helical strips were recorde d. The resting tension was set at 0.7 g, 1.2 g or 2.5 g. Endothelium-preser ved strips were precontracted with either phenylephrine or prostaglandin F- 2 alpha (PGF(2 alpha)). 3 In control conditions, acetylcholine (ACh) dose-dependently relaxed pheny lephrine-precontracted strips independently of resting tension. 4 At 0.7 g resting tension, nitric oxide synthase (NOS) inhibitors did not reduce ACh-induced relaxation, while either a guanylyl cyclase inhibitor or a NO trapping agent prevented it. At 1.2 g and 2.5 g resting tensions, NOS inhibitors shifted the ACh dose-response curve to the right. 5 After preincubation with indomethacin 15 muM) or ibuprofen (10 and 100 mu M). at 0.7 g and 1.2 g resting tensions, ACh induced an endothelium-depende nt, dose-dependent contraction. ACh (10(-6) M) increased the contraction up to two times greater the phenylephrine-induced one. Lipoxygenase inhibitor s prevented it. At high stretch, the ACh vasorelaxant effect was marginally influenced by cyclooxygenase (COX) inhibition. Similar results were obtain ed when aortic strips were precontracted with PGF(2 alpha). 6 Our data indicate that when resting tension is low. ACh mobilizes a store d NO pool that, synergistically with COX-derived metabolites, can relax pre contracted strips. COX inhibition upregulates the lipoxygenase metabolic pa thway, accounting for the ACh contractile effect. At an intermediate restin g tension, NO production is present, but COX inhibition reveals a lipoxygen ase dependent, ACh-induced contraction. At high resting tension, NO synthes is predominates and COX metabolites influence ACh-induced relaxation margin ally.