Inhibition of vascular smooth muscle tone by the H+, K+-ATPase inhibitor SCH 28080.
Vascular smooth muscle is thought to possess an H+-K+ ATPase that contributes to the regulation of intracellular K+ concentration and pH. We have examined the effect of the H+, K+-ATPase inhibitor SCH 28080 on vascular smooth muscle tone in guinea-pig and human isolated arteries, and on 86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. SCH 28080 (0.1-300 microM) produced relaxation of isolated guinea-pig aorta, guinea-pig pulmonary artery and human pulmonary artery. Relaxation occurred in tissues pre-contracted with phenylephrine, histamine or the thromboxane mimetic U44069. Relaxation. was reversible, and was not affected by tetrodotoxin, indomethacin, nordihydroguiaretic acid (NDGA), 1-aminobenzotriazole (1-ABT), N(G)-nitro-L-arginine methyl ester (L-NAME), removal of the endothelium or removal of extracellular K+. SCH 28080 had no effect on 86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. In conclusion, SCH 28080 relaxes vascular smooth muscle at concentrations known to inhibit the H+-K+ ATPase. The persistence of relaxation in a K+-free medium and the failure of SCH 28080 to inhibit 86Rb+ uptake suggest that relaxation may be unrelated to H+, K+-ATPase inhibition, and indicate that this agent may not be considered as a selective H+, K+-ATPase inhibitor in vascular preparations.
Rhoden
K J
KJ
Department. Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA. krhoden@jbpierce.org
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D054328:Proton Pump Inhibitors; D012413:Rubidium / Q000378:metabolism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D054328:Proton Pump Inhibitors; C035235:Sch 28080; D012413:Rubidium