Stimulation of alpha 2-adrenoreceptors blunts the phosphaturic response to parathyroid hormone

Acute renal denervation is phosphaturic and enhances the phosphaturic response to parathyroid hormone (PTH). Stimulation of alpha-adrenoreceptors inhibits the renal accumulation of 3,5-cyclic adenosine monophosphate (cAMP) in response to PTH. However, the effect of this blunted cAMP response by stimulation of alpha-adrenoreceptors on the phosphaturic response to PTH is not well understood. Therefore, the effect of alpha-adrenergic stimulation on the phosphaturic response to PTH was studied by infusion of PTH in the presence and absence of epinephrine plus propranolol. Sprague-Dawley rats were acutely thyroparathyroidectomized, and the left kidney was denervated. Stimulation of alpha-adrenoreceptors significantly blunted the phosphaturic response to PTH, decreasing the change in fractional excretion of phosphate (delta FEp) (21.2% +/- 1.3%, n = 8), as compared with the response to PTH alone (FEp, 30.0% +/- 2.4%, n = 7). In subsequent studies, yohimbine (an alpha 2-adrenoreceptor antagonist) or prazosin (an alpha 1-antagonist) were infused to dissociate alpha 1 from alpha 2-adrenoreceptor activity. Coadministration of yohimbine tended to restore the blunted phosphaturic response to PTH induced by alpha-adrenergic stimulation (delta FEp, 25.8% +/- 2.4%, n = 9), whereas addition of prazosin did not affect the blunted response (delta FEp, 16.1% +/- 4.5%, n = 7). We conclude that stimulation of alpha-adrenoreceptors blunts the phosphaturic response to PTH, most likely due to enhanced alpha 2-adrenoreceptor activity.