title: Aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle.
abstract: Aldosterone increases cation transport and contractility of vascular smooth muscle, but the specific transporter involved and how it is linked to smooth muscle tone is unknown. Because the Na-K-2Cl cotransporter (NKCC1) contributes to vascular smooth muscle contraction and is regulated by vasoactive compounds, we sought to determine whether this transporter is a target of aldosterone in rat aorta. Treatment of adrenalectomized rats with aldosterone for 7 days resulted in a 63% increase in NKCC1 activity as measured by bumetanide-sensitive efflux of 86Rb+. Treatment of normal aortas in culture with aldosterone for 3 and 7 days resulted in 29% and 47% increases in NKCC1 activity, respectively. Aldosterone had no acute effect on 86Rb+ efflux. Stimulation of NKCC1 was blocked by spironolactone, a mineralocorticoid receptor antagonist, but not by RU38486, a glucocorticoid receptor antagonist. Aldosterone did not augment the stimulation of NKCC1 by phenylephrine and did not increase NKCC1 mRNA as determined by real-time polymerase chain reaction. We conclude that aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle through classic mineralocorticoid receptors but not through changes in the abundance of NKCC1 mRNA. This could account for the increase in Na+, K+, and Cl- fluxes previously observed in vascular smooth muscle from mineralocorticoid-treated animals and may contribute to increased vascular tone.
authors.affiliation: Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Ga 30322, USA.
authors.forename: Gengru
authors.initials: G
authors.lastname: Jiang
authors.forename: Scott
authors.initials: S
authors.lastname: Cobbs
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: W Charles
authors.initials: WC
authors.lastname: O'Neill
mesh_terms: D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D012414:Rubidium Radioisotopes; D028021:Sodium-Potassium-Chloride Symporters; D014662:Vasoconstrictor Agents; D002034:Bumetanide; D010656:Phenylephrine; D013148:Spironolactone; D000450:Aldosterone