Candesartan ameliorated salt-related structural and functional cardiac and renal abnormalities in spontaneously hypertensive rats without reducing arterial pressure.
Does candesartan prevent target organ damage in salt-loaded spontaneously hypertensive rats?
AT1 receptor antagonism with candesartan ameliorates salt-induced structural and functional cardiac and renal abnormalities in spontaneously hypertensive rats independently of arterial pressure reduction.
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 (AT(1)) 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 AT(1) receptors), at least in part, participated importantly in the pressure-independent effects of salt excess on target organ damage of hypertension.
Varagić et al. (Sat,) conducted a other in Hypertension and salt-induced target organ damage. Candesartan vs. 8% salt diet alone and standard chow controls was evaluated on Arterial pressure and target organ damage (LV remodeling, myocardial fibrosis, LV diastolic dysfunction). Candesartan ameliorated salt-related structural and functional cardiac and renal abnormalities in spontaneously hypertensive rats without reducing arterial pressure.