Stimulatory action of parathyroid hormone on renin secretion in vitro: a study using isolated rat kidney, isolated rabbit glomeruli and superfused dispersed rat juxtaglomerular cells

Abstract

1. We have previously reported that pharmacological concentrations (125nmol/l) of parathyroid hormone may stimulate renin release in the stable recirculating and non-filtering isolated rat kidney. 2. In the present study we have attempted to extend these initial observations by examining the concentration-related response of renin release to parathyroid hormone, using the same model of isolated kidney, and determining whether the effect of parathyroid hormone on renin release can be demonstrated by more direct approaches. Thus, the effects of parathyroid hormone on renin secretion were investigated in two other renal preparations: isolated rabbit glomeruli and isolated rat juxtaglomerular cells. 3. In the isolated kidney, rat parathyroid hormone significantly stimulated renin accumulation in the perfusate in a concentration-related manner with a threshold of 1 nmol/l. 4. In both glomeruli and juxtaglomerular cells bovine [Nle8,18,Tyr34]parathyroid hormone-(1-34)amide effectively and repeatedly stimulated renin release. These results imply that there is a direct stimulatory effect of parathyroid hormone on renin release. 5. We also examined the effect of [Nle8,18,Tyr34]parathyroid hormone-(1-34)amide during extracellular calcium buffering in the glomeruli. [Nle8,18,Tyr34]parathyroid hormone-(1-34)amide was uneffective in calcium-free medium. Increasing the extracellular ionized calcium concentration to 2.5 mmol/l increased the extent of stimulation in accordance with the reported ability of parathyroid hormone to block calcium channels and relax vascular smooth muscle cells. 6. These results provide further support for the role of parathyroid hormone as a direct mediator of renin secretion; moreover, the renin-stimulating action of parathyroid hormone may be mediated through the inhibition of calcium influx.

Vascular effects of parathyroid hormone and parathyroid hormone‐related protein in the split hydronephrotic rat kidney.

“…In addition, the presence of speeific receptors for PTH and PTHRP on renal arterioles (Nickols et al 1990), the direct potent stimulatory effects of PTH (Helwig et al 1991;Saussine et al 1993a) and PTHRP (Saussine et al 1993b) on renin release, together with the regulation of PTHRP production in vascular smooth muscle cells by growth factors and vasoconstrictors including angiotensin II (Pirola et al 1993), strongly implicate this protein as a locally active autocrine/paracrine factor. Nevertheless, whether the vascular tree of the kidney is able to produce and secrete PTHRP and whether the renovascular properties of PTHRP are physiologically relevant is actually unknown.…”

Prognostic Value of Serum Parathyroid Hormone Level in Acute Decompensated Heart Failure

“…Small increases within the physiological range in PTH level reportedly improved the contractile performance of adult rat ventricular cardiomyocytes. 18 Hyperparathyroidism stimulates the synthesis of renin in juxtaglomerular cells 21 and aldosterone in zona glomerulosa cells 22 by increasing intracellular Ca 2+ level. In addition, activation of the adrenergic nervous system with a resultant elevation in circulating catecholamines facilitates To evaluate the heterogeneity of the prognostic value of lownormal PTH on admission, subgroup analysis was performed.…”

Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake

“…The renin-angiotensin system acts to homeostatically maintain blood pressure in response to reduced renal perfusion pressure (34,41), increased renal sympathetic nerve activity (43), or reduced NaCl intake (5,10,24). Previous studies have suggested that exogenous PTHrP may stimulate renin secretion in the isolated perfused kidney model (35).…”

“…PTH, acting on the common PTH/PTHrP receptor, has been reported to stimulate renin release directly from juxtaglomerular (JG) cells (34). Similarly, it has been reported that PTHrP can acutely stimulate renin release from the isolated perfused kidney at pharmacological concentrations, suggesting an effect of PTHrP on the endothelium or JG cells to directly stimulate renin release (35).…”