Inhibition of aldosterone production and angiotensin action by drugs affecting potassium channels.
We screened potassium channel agonists and antagonists in a search for pharmacologic probes of the channels that mediate potassium's effects on adrenal zona glomerulosa cells. Suspensions of bovine cells were tested, and aldosterone was measured by radioimmunoassay. The most potent inhibitors were pinacidil, capsaicin, glyburide, and quinine. These reagents were more potent against aldosterone production than against cortisol production. Aldosterone produced under basal conditions, as well as that stimulated by potassium, angiotensin II, or dibutyryl cyclic AMP, was antagonized. The vasodilatory and aldosterone-inhibiting potencies of potassium channel reagents were very different. Candidate antihypertensives with potassium channel activity should be tested for adrenal inhibition.
Hadjokas
N
N
William S. Middleton Memorial Veterans Hospital, Madison, Wisc.
Goodfriend
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002417:Cattle; D000451:Mineralocorticoid Receptor Antagonists; D015221:Potassium Channels / Q000187:drug effects*; D011863:Radioimmunoassay; D014665:Vasodilator Agents / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000187:drug effects*
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D015221:Potassium Channels; D014665:Vasodilator Agents; D000804:Angiotensin II; D000450:Aldosterone; D000255:Adenosine Triphosphate