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Pnas proceedings of the national academy of sciences of the united states of america skip to main page content info for authors editorial board about subscribe advertise contact feedback site map task channel deletion in mice causes primary hyperaldosteronism lucinda a. Davies *, changlong hu *, nick a. Guagliardo † , neil sen *, xiangdong chen *, edmund m. Talley * , ‡ , robert m. Carey † , douglas a. Bayliss * , ⧠, ⶠ, and paula q. Barrett * , ⧠, ⶠdepartments of *pharmacology, †internal medicine, and â§anesthesiology, university of virginia school of medicine, charlottesville, va 22908 communicated by gerhard giebisch, yale university school of medicine, new haven, ct, december 19, 2007 (received for review november 1, 2007) abstract when inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. viagra online Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (zg) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of twik-related acid-sensitive k (task)-1 and task-3 channels removes an important background k current that results in a marked depolarization of zg cell membrane potential. Although task channel deletion mice (task−/−) adjust urinary na excretion and aldosterone production to match na intake, they produce more aldosterone than control mice across the range of na intake. tips for buying viagra online Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of na intake. In addition, task−/− mice fail to suppress aldosterone production in response to dietary na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in task−/− mice. Thus, task−/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. tips for buying viagra online Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify task channels as a possible therapeutic target for primary hyperaldosteronism. Potassium channels adrenal glomerulosa cells renin aldosterone footnotes â¶to whom correspondence may be addressed. viagra without a doctor prescription E-mail: dab3y{at}virginia. Edu or pqb4b{at}virginia. Edu author contributions: l. A. buy viagra online D. , e. M. T. generic viagra online , r. M. C. , d. A. Natural remedies for viagra B. How are viagra and viagra different , and p. viagra for sale Q. best results from viagra B. Designed research; l. cheap generic viagra A. generic viagra rx D. , c. H. , n. A. viagra scary movie 4 G. , n. S. , and e. M. can take 40 mg viagra T. cheap viagra Performed research; x. C. buy cheap viagra , e. M. T. , d. A. B. , and p. Q. getting viagra legally uk B. Contributed new reagents. Women taking men's viagra
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