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Chronic parathyroid hormone‐related protein induces hypercalcemia and increases plasma renin activity

Parathyroid hormone‐related protein (PTHrP) increases renin release from isolated perfused kidneys, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia, weight loss and polyuria, all of which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) by reducing salt and caloric intake. We infused male Sprague‐Dawley rats with vehicle or PTHrP via subcutaneous osmotic‐mini pumps for 5 days. PTHrP increased PRA from 3.6±0.7 to 14.9±8.2 ng Ang I/ml/hr (p<0.05), increased plasma calcium from 13.1±0.06 to 17.6±0.08 mg/dl (p<0.05), decreased body weight from 263 to 220 g (p<0.05) and caused polyuria (control: 14.5±2.6 vs. PTHrP: 34.5±6.5 ml urine/24 hrs, p<0.05). To attenuate the PTHrP‐induced anorexia, we gave PTHrP‐treated rats dietary caloric supplementation which attenuated the weight loss and decreased PTHrP‐stimulated PRA from 19.5±5.8 to 5.9±1.3 ng Ang I/ml/hr, but did not affect the hypercalcemia nor polyuria. Our data suggests chronically elevated PTHrP increases PRA, not via a calcium effect but possibly via its anorexic effects on salt and caloric homeostasis. Funded by 5F30DK084654‐03 and 5P01HL090550‐03.