TITLE

Collecting duct--specific knockout of endothelin-1 causes hypertension and sodium retention

AUTHOR(S)
Ahn, Dowhan; Yuqiang Ge; Stricklett, Peter K.; Gill, Pritmohinder; Taylor, Deborah; Hughes, Alisa K.; Yanagisawa, Masashi; Miller, Lance; Nelson, Raoul D.; Kohan, Donald E.
PUB. DATE
August 2004
SOURCE
Journal of Clinical Investigation;Aug2004, Vol. 114 Issue 4, p504
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
In vitro studies suggest that collecting duct-derived (CD-derived) endothelin-1 (ET-1) can regulate renal Na reabsorption; however, the physiologic role of CD-derived ET-1 is unknown. Consequently, the physiologic effect of selective disruption of the ET-1 gene in the CD of mice was determined. Mice heterozygous for aquaporin2 promoter Cre recombinase and homozygous for loxP-flanked exon 2 of the ET-1 gene (called CD-specific KO of ET-1 [CD ET-1 KO] mice) were generated. These animals had no CD ET-1 mRNA and had reduced urinary ET-1 excretion. CD ET-1 KO mice on a normal Na diet were hypertensive, while body weight, Na excretion, urinary aldosterone excretion, and plasma renin activity were unchanged. CD ET-1 KO mice on a high-Na diet had worsened hypertension, reduced urinary Na excretion, and excessive weight gain, but showed no differences between aldosterone excretion and plasma renin activity. Amiloride or furosemide reduced BP in CD ET-1 KO mice on a normal or high-Na diet and prevented excessive Na retention in salt-loaded CD ET-1 KO mice. These studies indicate that CD-derived ET-1 is an important physiologic regulator of renal Na excretion and systemic BP.
ACCESSION #
14163017

 

Related Articles

  • Role of Endothelin in the Pathogenesis of Hypertension. del Villar, Candelas Perez; Alonso, Carlos Javier Garcia; Feldstein, Carlos A.; Juncos, Luis A.; Romero, J. Carlos // Mayo Clinic Proceedings;Jan2005, Vol. 80 Issue 1, p84 

    In 1985, Investigators characterized a potent vasoconstrictor of endothelial origin called endothelin (ET). Subsequently, 3 peptides were recognized that had a comparable molecular structure but different receptors that mediate potent vasoconstrictive and mild vasodilative effects. The renal...

  • Age versus urinary sodium for judging renin, aldosterone, and catecholamine levels: Studies in normal subjects and patients with essential hypertension. Weidmann, Peter; Beretta-Piccoli, Carlo; Ziegler, Walter H.; Keusch, Gerald; Glück, Zeev; Reubi, François C. // Kidney International;Dec1978, Vol. 14 Issue 6, p619 

    The relative influence of sodium balance and age on plasma renin activity (PRA), aldosterone (PA), norepinephrine (NE). and epinephrine (E) levels, and urinary NE or E measured in an outpatient setting was evaluated in 90 normal subjects and 79 patients with benign essential hypertension. Ranges...

  • Aldosterone synthase inhibitors in hypertension: current status and future possibilities. Hargovan, Milan; Ferro, Albert // JRSM Cardiovascular Disease;Jan-Dec2014, Vol. 3, p1 

    The renin-angiotensin aldosterone system is a critical mechanism for controlling blood pressure, and exerts most of its physiological effects through the action of angiotensin II. In addition to increasing blood pressure by increasing vascular resistance, angiotensin II also stimulates...

  • The renin-aldosterone system during normal and hypertensive pregnancy. Elsheikh, A.; Creatsas, G.; Mastorakos, G.; Milingos, S.; Loutradis, D.; Michalas, S. // Archives of Gynecology & Obstetrics;Jan2001, Vol. 264 Issue 4, p182 

    Gestational hypertension complicates approximately 5%–7% of pregnancies and it may be deleterious to both maternal and fetal health. Gestational hypertension is a multisystem disorder which always resolves itself after delivery; its primary pathology still remains incompletely clarified....

  • Effect of a Selective Endothelin Receptor A Blocker on Cardiovascular Remodeling in Uninephrectomized Spontaneously Hypertensive Rats of the Stroke-Prone Strain. Orth, Stephan R.; Schiele, Günter; Banas, Bernhard; Ritz, Eberhard; Amann, Kerstin // Kidney & Blood Pressure Research;2007, Vol. 30 Issue 6, p400 

    Background/Aims: The role of endothelin (ET) in cardiovascular remodeling was investigated by treating uninephrectomized spontaneously hypertensive rats of the stroke-prone strain (UNX-SHRsp) on normal- or high (3%)-salt diet with the selective ETA receptor blocker LU 135252. Methods: SHRsp on...

  • Conn's Syndrome: A Diagnostic Dilemma. Case Report. Butt, Waqas Tariq; Butt, Muhammad Umer; Gauhar, Tooba Mahmud; Khawaja, Ali Azim; Afzal, Ameer; Ahmed, Ashfaq; Azim, Khawaja Muhammad // Internet Journal of Surgery;2010, Vol. 24 Issue 1, p1 

    Conn's syndrome or primary hyperaldosteronism is characterized by hypertension, hypokalemia and increased ratio of plasma aldosterone concentration (ng/dl) to plasma renin activity (ng/ml per hour). Primary aldosteronism occurs most commonly due to aldosterone producing adenoma (Conn's syndrome)...

  • Primary Hyperaldosteronism in the Hypertensive Disease. Fardella, Carlos E.; Carvajal, Cristian A.; Mosso, Lorena M. // Current Hypertension Reviews;2006, Vol. 2 Issue 1, p33 

    Primary aldosteronism (PA) is one of the potentially curable forms of hypertension. The hypertension is secondary to aldosterone action in the kidney, reabsorbing sodium and water that increases the intravascular volume and blood pressure. PA was previously believed to account for less than 1%...

  • The Resurgence of Aldosterone in Hypertension and Cardiovascular Disease. Freel, E. Marie; Connell, John M. C. // Current Hypertension Reviews;2006, Vol. 2 Issue 1, p21 

    Aldosterone is a key cardiovascular hormone. Recent studies have illustrated its role in cardiac fibrosis and left ventricular hypertrophy as well as in impaired vascular reactivity. Moreover, many of these actions have been shown to be independent of its known effects on blood pressure. In a...

  • Nitric Oxide Mediates Vasoactive Effects of Endothelin-3 on Rat Mesenteric Microvascular Beds in Vivo. Kurose, Iwao; Fukumura, Dai; Miura, Soichiro; Sekizuka, Eiichi; Nagata, Hiroshi; Suematsu, Makoto; Tsuchiya, Masaharu // Angiology;Jun1993, Vol. 44 Issue 6, p483 

    In order to clarify whether the vasoactive effects of endothelin-3 (ET-3) on microvessels are associated with the endothelium-derived relaxing factor (EDRF) in vivo, the authors examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics