dinoprost and 6-anilino-5-8-quinolinedione

1. Since the role of mechanical stretches in vascular tone regulation is poorly understood, we studied how stretch can influence endothelial tone. 2. Isometric contractions of isolated rat aortic helical strips were recorded. The resting tension was set at 0.7 g, 1.2 g or 2.5 g. Endothelium-preserved strips were precontracted with either phenylephrine or prostaglandin F(2 alpha) (PGF(2 alpha)). 3. In control conditions, acetylcholine (ACh) dose-dependently relaxed phenylephrine-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 (5 microM) or ibuprofen (10 and 100 microM), at 0.7 g and 1.2 g resting tensions, ACh induced an endothelium-dependent, dose-dependent contraction. ACh (10(-6) M) increased the contraction up to two times greater the phenylephrine-induced one. Lipoxygenase inhibitors prevented it. At high stretch, the ACh vasorelaxant effect was marginally influenced by cyclooxygenase (COX) inhibition. Similar results were obtained when aortic strips were precontracted with PGF(2 alpha). 6. Our data indicate that when resting tension is low, ACh mobilizes a stored NO pool that, synergistically with COX-derived metabolites, can relax precontracted strips. COX inhibition up-regulates the lipoxygenase metabolic pathway, accounting for the ACh contractile effect. At an intermediate resting tension, NO production is present, but COX inhibition reveals a lipoxygenase-dependent, ACh-induced contraction. At high resting tension, NO synthesis predominates and COX metabolites influence ACh-induced relaxation marginally.

Topics: Acetylcholine; Aminoquinolines; Animals; Aorta, Thoracic; Cyclooxygenase Inhibitors; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Fatty Acids, Unsaturated; Guanylate Cyclase; Ibuprofen; In Vitro Techniques; Indoles; Indomethacin; Lipoxygenase Inhibitors; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; omega-N-Methylarginine; Phenylephrine; Rats; Rats, Wistar; Stress, Mechanical; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

Hypoxia causes complex changes in vascular tone of isolated blood vessels. This study was performed in rings with and without endothelium of rat abdominal aortas and canine coronary arteries suspended in organ chambers for isometric tension recording. In both aortic and coronary rings with endothelium precontracted with a half-maximal concentration of phenylephrine or prostaglandin F2 alpha, respectively, hypoxia induced transient relaxations (20 +/- 2 and 15 +/- 3%, respectively); removal of the endothelium prevented the response in aortas, but not coronary arteries. The transient hypoxic relaxation was followed in both preparations by endothelium-dependent contractions (EDCs). Hypoxic relaxations were prevented by indomethacin (10 microM) in canine arteries, but not in rat aortas. The inhibitor of nitric oxide (NO) synthase, N omega-nitro-L-arginine (30 microM), inhibited hypoxic relaxations in intact rat aortas, but left those in coronary arteries unchanged. Similar results were obtained with methylene blue and LY 83583. In preparations without endothelium, sodium nitroprusside (30 nM) elicited a reappearance of hypoxic relaxations in the rat but not the dog coronary artery. Thus, hypoxic relaxation is mediated by a prostaglandin in the dog coronary artery, but by endothelium-derived NO in the rat aorta. As the response was dependent on the level of contraction, this suggests that the release or action of NO decreases with increasing tone.

Topics: Aminoquinolines; Animals; Aorta, Abdominal; Arginine; Coronary Vessels; Dinoprost; Dogs; Endothelium, Vascular; In Vitro Techniques; Methylene Blue; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Nitroarginine; Norepinephrine; Oxygen; Rats; SRS-A; Vascular Resistance; Vasodilation

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

Topics: Acetylcholine; Aminoquinolines; Animals; Calcimycin; Catalase; Dinoprost; Dogs; Femoral Vein; Hemoglobins; In Vitro Techniques; Indomethacin; Methylene Blue; Muscle, Smooth, Vascular; Nitric Oxide; Norepinephrine; Ouabain; Potassium; SRS-A; Superoxide Dismutase; Vasodilation