CALL FOR PAPERS Integrative Aspects of Renal Endocrinology Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake

Atchison DK, Westrick E, Szandzik DL, Gordish KL, Beierwaltes WH. Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake. Am J Physiol Endocrinol Metab 303: E457–E463, 2012. First published May 29, 2012; doi:10.1152/ajpendo.00020.2012.—Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-Dawley rats with the vehicle (control) or 125 g PTHrP/day (PTHrP) via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a third group of PTHrP-infused rats received 0.3% NaCl (PTHrP NaCl) in their drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4 ng Ang I·ml ·h 1 (P 0.05), whereas the median PTHrP NaCl PRA value was normal (7.82 ng Ang I·ml ·h , P 0.05 vs. PTHrP). Plasma Ca (median control: 10.2 mg/dl; PTHrP: 13.7 mg/dl; PTHrP NaCl: 14.1 mg/dl; P 0.05) and PTHrP (median control: 0.03 ng/ml; PTHrP: 0.12 ng/ml; PTHrP NaCl: 0.15 ng/ml; P 0.05) were elevated in PTHrPand PTHrP NaCl-treated rats. Body weights and caloric consumption were lower in PTHrPand PTHrP NaCltreated rats. NaCl consumption was lower in PTHrP-treated rats (mean Na : 28.5 4.1 mg/day; mean Cl : 47.8 mg/day) compared with controls (Na : 67.3 2.7 mg/day; Cl : 112.8 4.6 mg/day; P 0.05). NaCl consumption was comparable with control in the PTHrP NaCl group; 0.3% NaCl in the drinking water had no effect on PRA in normal rats. Thus, our data support the hypothesis that PTHrP increases PRA via its anorexic effects, reducing NaCl intake and causing NaCl restriction.