Involvement of endothelium in vasodilating effects of vintoperol.
Experiments were performed on vessels of the femoral vascular bed of anesthetized dogs and on isolated rings of the rat pulmonary artery, vena cava, and thoracic aorta. Vintoperol was administered intra-arterially (0.01, 0.1, and 0.3 mg/kg/min for 10 min) or added in vitro (10(-4) M). De-endothelialization by saponin (0.5 mg/ml for 5 min) of intact vascular beds or mechanical endothelium removal in rings decreased vasodilation or relaxation by 50-60% vs. control. In de-endothelialized vascular beds, vintoperol (0.3 mg/kg/min) increased blood flow by 18 +/- 5% but 47 +/- 4% under control conditions (p < 0.05). Methylene blue (10 mg/kg) reduced the increment of blood flow to vintoperol from 47 +/- 4 to 24 +/- 4% (p < 0.05). After de-endothelialization of the isolated pulmonary artery, relaxation of precontracted segments was reduced (21 +/- 4% vs. 56 +/- 5% under control conditions; p < 0.05). Vintoperol-induced relaxation of vascular rings was also inhibited by gossypol (2 x 10(-5) M) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) depended on the duration of exposure to the inhibitors. In conclusion, relaxation to vintoperol must be mediated by the release of endothelium-derived nitric oxide.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects; D006072:Gossypol / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D007211:Indoles; D011807:Quinolizines; D014665:Vasodilator Agents; D010208:Papaverine; C066359:vintoperol; D006072:Gossypol; D008751:Methylene Blue