Published Online
on March 31, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on July 1, 2002
Revised on July 30, 2002

Aldosterone Regulates the Na-K-2Cl Cotransporter in Vascular Smooth Muscle

Gengru Jiang; Scott Cobbs; Janet D. Klein; and W. Charles O'Neill^*

From the Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Ga.

^* To whom correspondence should be addressed. E-mail: woneill{at}emory.edu.

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.

Key words: aldosterone • muscle, smooth, vascular • rats • hypertension, mineralocorticoid • vasoconstriction

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