Abstract 529: Treatment With Telmisartan Inhibits Kidney Injury in High Salt-loading Tsukuba Hypertensive Mice With Attenuation of Sympathetic Nervous System

Abstract

Objective: It is well known that excessive salt intake and/or activation of renin-angiotensin system (RAS) increases blood pressure in part via an increase in sympathetic nerve activity. To further examine the interaction of these factors, we employed transgenic mice carrying both the human renin and angiotensinogen genes (Tsukuba hypertensive mice) and studied the effects of high salt loading and telmisartan on mortality, blood pressure and kidney functions. Design and Method: Ten-week-old male Tsukuba hypertensive mice (TH) were administrated control chow or the chow containing 8% NaCl with or without telmisartan (1 mg/kg/day) and PPAR-γ antagonist, GW9662, in drinking water for 8 weeks. Blood pressure was assessed by radio telemetry method. Urine samples were obtained before and after salt-loading. Concentrations of urinary adrenalin and noradrenalin were measured by ELISA. Expressions of ENaC-α, P47 and p67-phox mRNA in the kidney were measured by RT-PCR. Results: Survival rate 8 weeks after treatment was decreased in salt-loading TH (sTH) mice compared with control TH (cTH). This decrease was improved by the treatment with telmisartan. Blood pressure in sTH mice was significantly higher compared with cTH mice and the treatment with telmisartan mice decreased blood pressure. Urinary sodium concentration was higher in sTH mice compared with cTH mice and treatment with telmisartan further increased urinary sodium concentration in sTH mice. Expression of ENaC-α in did not between sTH mice and cTH mice. Treatment with telmisartan decreased expression of ENaC-α. Urinary adrenalin and noradrenalin concentrations were higher in sTH mice compared with cTH mice. These increases were attenuated by treatment with telmisartan. Expressions of p47 and p67-phox in sTH mice were increased more markedly compared with cTH mice. These increase were also attenuated by treatment with telmisartan. However, these possible protective effects of telmisartan were not influenced by the co-treatment with GW9662. Conclusion: These results suggested that salt-loading enhanced an increase in blood pressure, superoxide anion production, sympathetic activity and mortality in concert with activated RAS.