{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:40:07Z","timestamp":1791092407327,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>Genomic mechanisms of steroid action have been increasingly elucidated over the past four decades. In contrast, rapid steroid actions have been widely recognized only recently, and detailed analysis of the mechanisms involved are still lacking. The present article describes rapid effects of mineralocorticoid hormones on free intracellular calcium in vascular smooth muscle cells as determined by fura 2 spectrofluorometry in single cultured cells from rat aorta. These effects are almost immediate and reach a plateau after only 3 to 5 minutes and are characterized by high specificity for mineralocorticoids versus glucocorticoids. The potent mineralocorticoids aldosterone and fludrocortisone are agonists with estimated apparent EC<jats:sub>50<\/jats:sub>values of \u22480.1 to 0.5 nmol\/L; deoxycorticosterone acetate is an agonist with an EC<jats:sub>50<\/jats:sub>of \u22485 nmol\/L; and progesterone, cortisol, corticosterone, and estradiol have much lower potency (EC<jats:sub>50<\/jats:sub>values of \u22480.5 to 5 \u03bcmol\/L). The effect of aldosterone is blocked by neomycin and short-term treatment with phorbol esters but augmented by staurosporine, indicating an involvement of phospholipase C and protein kinase C. The Ca<jats:sup>2+<\/jats:sup>effect appears to involve the release of intracellular Ca<jats:sup>2+<\/jats:sup>, as shown by the inhibitory effect of thapsigargin; intriguingly, a relatively small maximum effect (\u224840 nmol\/L increase) is consistently seen. This mechanism operates at physiological subnanomolar aldosterone concentrations and appears to be a likely candidate for rapid fine tuning of cardiovascular responsivity. It may also contribute to known clinical features of mineralocorticoid action that are difficult to explain by the traditional genomic mechanism alone.<\/jats:p>","DOI":"10.1161\/01.res.76.6.973","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"973-979","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["Nongenomic Effects of Aldosterone on Intracellular Ca<sup>2+<\/sup>in Vascular Smooth Muscle Cells"],"prefix":"10.1161","volume":"76","author":[{"given":"Martin","family":"Wehling","sequence":"first","affiliation":[{"name":"From the Baker Medical Research Institute, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig B.","family":"Neylon","sequence":"additional","affiliation":[{"name":"From the Baker Medical Research Institute, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryl","family":"Fullerton","sequence":"additional","affiliation":[{"name":"From the Baker Medical Research Institute, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Bobik","sequence":"additional","affiliation":[{"name":"From the Baker Medical Research Institute, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Funder","sequence":"additional","affiliation":[{"name":"From the Baker Medical Research Institute, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"268","volume":"23","year":"1987","unstructured":"Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman D, Evans RM. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987;23:268-275.","journal-title":"Science"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-3-11-1877"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1987.252.5.C505"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(90)90010-R"},{"key":"e_1_3_2_5_2","first-page":"E170","volume":"257","year":"1989","unstructured":"Wehling M, Kuhls S, Armanini D. Volume regulation of human lymphocytes by aldosterone in isotonic medium. Am J Physiol. 1989;257:E170-E174.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1991.260.5.E719"},{"key":"e_1_3_2_7_2","first-page":"1452","volume":"77","year":"1993","unstructured":"Christ M, Eisen C, Aktas J, Theisen K, Wehling M. The inositol-1,4,5-trisphosphate system is involved in rapid effects of aldosterone in human mononuclear leukocytes. J Clin Endocrinol Metab. 1993;77:1452-1457.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.1.117"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.5.1464"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90233-B"},{"key":"e_1_3_2_11_2","first-page":"E974","volume":"263","year":"1992","unstructured":"Wehling M, Christ M, Theisen K. Membrane receptors for aldosterone: a novel pathway for mineralocorticoid action. 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