Renal Actions of Neutral Endopeptidase Inhibition and Its Effects on Gene Expression of Atrial Natriuretic Peptide and Neutral Endopeptidase in Rats with Chronic Heart Failure | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Article 12, Volume 30, Issue 1, December 2010, Pages 185-206 PDF (289.51 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2010.36173 | ||
| Authors | ||
| Ayman Elsamanoudy* 1; Amr Abbas2 | ||
| 1Department of Medical Biochemistry , Faculty of Medicine, Mansoura University, Egypt | ||
| 2Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt | ||
| Abstract | ||
| Background and Aim of work: The aim of the current study is to evaluate the effects of acute and chronic inhibition of NEP, by ONO-9902, on ANP, and NEP gene expressions, hemodynamic and renal parameters in rats with chronic heart failure (CHF) following left coronary artery ligation (CAL). Methods: The study comprised 48 male Sprague-Dawley rats (220–240 g) which were divided into sham and CAL groups. Myocardial infarction was induced by left CAL. All rats were divided into untreated and orally treated with ONO-9902 (300 mg/kg/day) from the 1st to 6th week after the operation At the 1st and 6th weeks after the operation, gene expression of ANP and NEP, plasma ANP, cGMP, and aldosterone concentrations, urine volume, Na and ANP excretion, creatinine clearance, renal cGMP generation, body and organ weight were measured. Results: CAL led to sodium and water retention, increased plasma level of ANP and aldosterone, in addition to increase in ANP gene expression as well as decrease in renal generation of cGMP. Acute treatment of rats with CAL by NEPI, at the first week after the operation, inhibited the NEP gene expression with increased plasma ANP concentration and gene expression, which caused diuresis and natriuresis and increased renal cGMP generation. Moreover, chronic treatment by NEPI caused significant decrease in lung weight, lung body weight ratio, NEP gene expression and PAC, non significant increase in plasma concentration and gene expression of ANP, diuresis and natriuresis with increased renal cGMP generation. GFR is not significantly changed either before or after treatment. Conclusions: It is concluded that gene expression and plasma level of ANP increased in CHF. Also, chronic treatment with NEP inhibitor improves pulmonary edema and decreases Na and water retention in rats with CHF by deceasing degradative effect of NEP on ANP which leads to prolongation of its bioactivity. So, ONO-9902 may offer a new therapeutic approach in patients with CHF. | ||
| Keywords | ||
| Heart failure; kidney; atrial natriuretic peptide; neutral endopeptidase; aldosterone; Rats | ||
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