Inhibition of calcium release of diazoxide studied in the isolated rat kidney
Slegers, J.F.; Förster, M.T.; Moons, W.M.
Archives Internationales de Pharmacodynamie et de Therapie 250(1): 147-163
1981
ISSN/ISBN: 0003-9780 PMID: 7271376 Document Number: 178050
Isolated kidneys of normotensive Wistar rats (NWR) and of genetically hypertensive Kyoto rats (SHR) were perfused. Contraction of intrarenal vascular smooth muscle cells were induced by Ba ions (0.1-1.0 mmol) and by high K concentrations (40 nmol). Ba stimulates intracellular Ca stores to release activator Ca. Repeated stimulation with Ba under Ca-free perfusion conditions depleted the stores. In kidneys of SHR rats the tension development in response to Ba was stronger as compared with NWR rats and the time needed to deplete the stores was prolonged. Smooth muscle cells of SHR rats contain more sequestered Ca. Diazoxide inhibited the Ba contracture rapidly, reversibly and dose dependently. The inhibition was non-competitive. Percentual inhibition was equal in NWR and in SHR rat kidneys. Diazoxide did not block the Ca influx across the sarcolemma membrane. The magnitude of the K contractures depended entirely upon the extracellular Ca concentration. In the range of 0.1-1.0 mmol Ca, tension development varied linearly with log Ca concentration. Diazoxide inhibited the K contractures, provided normally filled Ca stores were available. Diazoxide apparently prevents intracellular Ca stores from releasing Ca. This action is the basic mechanism of the vasodilating activity of diazoxide in smooth muscle cells of rat intrarenal vessels.