Glucocorticoids inhibit the expression of calcium-dependent potassium channels in vascular smooth muscle.
Increased calcium-activated potassium channel (KCa) activity in vascular smooth muscle (VSM) cells leads to a relaxation response counteracting the effects of high blood pressure. Since chronic exposure to glucocorticoids (GC) can be associated with an increase in blood pressure, we reasoned that GCs might modify the expression of KCa channels resulting in a net rise in vascular tone. To test this hypothesis, primary cultures of rat VSM cells were exposed to (a) RU 28362 (a pure glucocorticoid receptor agonist), 1 microM; (b) corticosterone 10 nM + carbenoxolone (an inhibitor of bidirectional VSM 11beta-OH steroid dehydrogenase), 1 microM; (c) 11-dehydrocorticosterone (a biologically inactive metabolite), 10 nM + carbenoxolone; (d) carbenoxolone alone; or (e) aldosterone 10 nM for periods of up to 72 h. Proteins were then extracted and Western blots prepared. Gels were probed with a rabbit-derived polyclonal antibody directed against KCa channel protein. The experimental procedure was repeated on separate sets of VSM cells to ensure reproducibility. Expression of KCa channel protein was diminished in VSM cells incubated with corticosterone + carbenoxolone and with RU 28362 after 24 h and remained low at 72 h. Expression of KCa protein in cells exposed to 11-dehydrocorticosterone + carbenoxolone, carbenoxolone alone, and aldosterone was either similar to controls or mildly increased over the 72 h. These data are consistent with the hypothesis that GCs diminish the expression of KCa protein. Diminished KCa expression could contribute to the observed increase in vascular tone following chronic GC exposure.
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002229:Carbenoxolone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D008901:Mineralocorticoids / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors