Cardiovascular effects of prorenin blockade in genetically spontaneously hypertensive rats on normal and high-salt diet.
نویسندگان
چکیده
Recent reports have demonstrated a potential role of tissue prorenin in the pathogenesis of cardiovascular and renal damage. This study was designed to examine the role of prorenin in the pathogenesis of target organ damage in spontaneously hypertensive rats (SHRs), the best naturally occurring experimental model of essential hypertension. To this end, we studied 20-wk-old male SHRs receiving a normal diet and 8-wk-old male SHRs given food with 8% NaCl. One-half the rats in each group were given prorenin inhibitor (PRAM-1, 0.1 mg.kg(-1).day(-1)) via osmotic minipumps; the other half served as controls. Arterial pressure, left ventricular function, cardiovascular mass indexes, cardiac fibrosis, and renal function were examined at the end of the experiment. Arterial pressure was unaffected by PRAM-1 in rats on either regular or salt-excess diets. In those rats receiving a normal diet, the blockade of prorenin activation consistently reduced left ventricular mass but affected no other variable. Salt-loaded rats given PRAM-1 for 8 wk demonstrated (1) reduced serum creatinine level, (2) decreased left ventricular mass, (3) improved left ventricular function, and (4) reduced left ventricular fibrosis. These data demonstrated that the blockade of nonproteolytic activation of prorenin exerted significant cardiovascular and renal benefit in SHRs with cardiovascular damage produced by salt excess and suggested that the activation of cardiovascular or renal prorenin may be a major mechanism that mediates cardiac and renal damage in this form of accelerated hypertension.
منابع مشابه
Cardiovascular Effects of Prorenin Blockade in Genetically Hypertensive Rats (shr) on Normal and High Salt Diet
متن کامل
Excessively low salt diet damages the heart through activation of cardiac (pro) renin receptor, renin-angiotensin-aldosterone, and sympatho-adrenal systems in spontaneously hypertensive rats
OBJECTIVE A high salt intake causes hypertension and leads to cardiovascular disease. Therefore, a low salt diet is now recommended to prevent hypertension and cardiovascular disease. However, it is still unknown whether an excessively low salt diet is beneficial or harmful for the heart. METHODS Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) received normal salt chow (0....
متن کاملEffects of a chronic high-salt diet on large artery structure: role of endogenous bradykinin.
Bradykinin activity could explain the blood pressure increase during NaCl loading in hypertensive animals, but its contribution on vascular structure was not evaluated. We determined cardiac mass and large artery structure after a chronic, 4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe-140. Four-week-old rats were divided into eight groups according to strain [s...
متن کاملCardiovascular effects of nonproteolytic activation of prorenin.
Cardiovascular Effects of Nonproteolytic Activation of Prorenin To the Editor: Several articles have appeared recently on the role of tissue prorenin in the pathogenesis of cardiovascular and renal damage in experimental models of hypertension and diabetes mellitus1–3 including the study by Ichihara et al,3 published in Hypertension and accompanied by an editorial comment.4 Thus, in rats with s...
متن کاملHigh Salt Intake Damages the Heart through Activation of Cardiac (Pro) Renin Receptors Even at an Early Stage of Hypertension
OBJECTIVE It has not yet been fully elucidated whether cardiac tissue levels of prorenin, renin and (P)RR are activated in hypertension with a high salt intake. We hypothesized that a high salt intake activates the cardiac tissue renin angiotensin system and prorenin-(pro)renin receptor system, and damages the heart at an early stage of hypertension. METHODS Wistar Kyoto rats (WKY) and sponta...
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عنوان ژورنال:
- American journal of physiology. Heart and circulatory physiology
دوره 295 3 شماره
صفحات -
تاریخ انتشار 2008