Comparison of the vascular relaxant effects of ATP-dependent K+ channel openers on aorta and pulmonary artery isolated from spontaneously hypertensive and Wistar-Kyoto rats

The vasorelaxant actions of adenosine 5'-triphosphate (ATP)-dependent K+ ch annel openers and sodium nitroprusside in isolated thoracic aorta and pulmo nary artery of spontaneously hypertensive rats (SHR) and normotensive Wista r-Kyoto (WKY) rats (14-18 weeks old) were investigated. Cumulative addition of sodium nitroprusside and different ATP-dependent K+ channel openers (pi nacidil, cromakalim, nicorandil, 2-(2 "(1 ",3 "-dioxolone)-2-methyl-4-(2'-o xo-l'-pyrrolidinyl)-6-nitro-2H-1-benzopyren (KR-30450) and aprikalim) to th ese preparations caused a concentration-dependent relaxation of noradrenali ne-pre-contracted aorta and pulmonary artery from both strains. The relativ e order of relaxation potency, estimated by comparing the IC50, was sodium nitroprusside > KR-30450 > aprikalim greater than or equal to cromakalim > pinacidil > nicorandil in pulmonary artery and aorta from both strains. At high concentrations (greater than or equal to 1 mu M), cromakalim, aprikali m and KR-30450 produced a greater percentage relaxation in SHR aorta than i n WKY aorta. However, there was no apparent difference between SHR and WKY in the relaxation response to all drugs tested on the pulmonary artery. The effects of cromakalim, aprikalim, pinacidil and KR-30450 observed in aorta and pulmonary artery were significantly attenuated by 3 mu M glibenclamide . 6-Anilino-5,8-quinolinequinone (LY 83583, 1 mu M), a soluble guanylate cy clase inhibitor, abolished the vasorelaxant effects of nicorandil and sodiu m nitroprusside. In conclusion, sodium nitroprusside and ATP-dependent K+ c hannel openers cause relaxation of noradrenaline-pre-contracted aorta and p ulmonary artery from both strains. However, all the drugs tested failed to cause selective relaxation of the pulmonary artery relative to the thoracic aorta. (C) 1999 Elsevier Science B.V. All rights reserved.