Is renal β-adrenergic-WNK4-NCC pathway important in salt hypertension of Dahl rats?

摘要

In 2011 Fujita and coworkers proposed that β-adrenergicstimulation causes decreased serine/threonine-protein kinaseWNK4 transcription leading to the activation of Na-Clcotransporter (NCC) which participates in salt sensitivity and salthypertension development in rodents. The aim of our study wasto investigate whether the above hypothesis is also valid for salthypertension of Dahl rats, which are characterized by highsympathetic tone and abnormal renal sodium handling. Male8-week-old salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahlrats were fed either low-salt diet (LS, 0.4 % NaCl) or high-saltdiet (HS, 4 % NaCl) for 6 weeks. Half of the animals on eitherdiet were chronically treated with non-selective β-blockerpropranolol (100 mg/kg/day). At the end of the experimentdiuresis and sodium excretion were measured prior and afterhydrochlorothiazide injection (HCTZ, 10 mg/kg i.p.).Furthermore, blood pressure (BP), heart rate (HR), sympathetic(pentolinium 5 mg/kg i.v.) and NO-dependent (L-NAME 30 mg/kgi.v.) BP components were determined. Chronic HS diet feedingincreased BP through sympathoexcitation in SS/Jr but not inSR/Jr rats. Concomitant propranolol treatment did not lower BPin either experimental group. Under the conditions of low saltintake HCTZ increased diuresis, natriuresis and fractional sodiumexcretion in SR/Jr but not in SS/Jr rats. HS diet feedingattenuated renal response to HCT in SR/Jr rats, whereasno HCTZ effect was observed in SS/Jr rats fed HS diet.Propranolol treatment did not modify diuresis or natriuresis inany experimental group. In conclusions, our present data do notsupport the idea on the essential importance of renalβ-adrenergic-WNK4-NCC pathway in pathogenesis and/ormaintenance of salt hypertension in Dahl rats.