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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/H853    most recent 00737.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Varagic, J. Articles by Díez, J. Search for Related Content PubMed PubMed Citation Articles by Varagic, J. Articles by Díez, J.

AT₁ receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure

¹Hypertension Research Laboratory, Ochsner Clinic Foundation, New Orleans, Louisiana; ²Hypertension and Vascular Research Center, Wake Forest University, School of Medicine, Winston-Salem, North Carolina; and ³Division of Cardiovascular Sciences, Centre for Applied Medical Research, and ⁴Department of Cardiology and Cardiovascular Surgery, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain

Submitted 26 June 2007 ; accepted in final form 29 November 2007

Our recent studies have demonstrated that salt excess in the spontaneously hypertensive rat (SHR) produces a modestly increased arterial pressure while promoting marked myocardial fibrosis and structural damage associated with altered coronary hemodynamics and ventricular function. The present study was designed to determine the efficacy of an angiotensin II type 1 (AT₁) receptor blocker (ARB) in the prevention of pressure increase and development of target organ damage from high dietary salt intake. Eight-week-old SHRs were given an 8% salt diet for 8 wk; their age- and gender-matched controls received standard chow. Some of the salt-loaded rats were treated concomitantly with ARB (candesartan; 10 mg·kg^–1·day^–1). The ARB failed to reduce the salt-induced rise in pressure, whereas it significantly attenuated left ventricular (LV) remodeling (mass and wall thicknesses), myocardial fibrosis (hydroxyproline concentration and collagen volume fraction), and the development of LV diastolic dysfunction, as shown by longer isovolumic relaxation time, decreased ratio of peak velocity of early to late diastolic waves, and slower LV relaxation (minimum first derivative of pressure over time/maximal LV pressure). Without affecting the increased pulse pressure by high salt intake, the ARB prevented the salt-induced deterioration of coronary and renal hemodynamics but not the arterial stiffening or hypertrophy (pulse wave velocity and aortic mass index). Additionally, candesartan prevented the salt-induced increase in kidney mass index and proteinuria. In conclusion, the ARB given concomitantly with dietary salt excess ameliorated salt-related structural and functional cardiac and renal abnormalities in SHRs without reducing arterial pressure. These data clearly demonstrated that angiotensin II (via AT₁ receptors), at least in part, participated importantly in the pressure-independent effects of salt excess on target organ damage of hypertension.

left ventricular function; fibrosis; coronary circulation; angiotensi II type 1 receptor blocker

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