PROPRANOLOL BLOCKS THE HYPOPHOSPHATURIA OF ACUTE RESPIRATORY ALKALOSIS IN HUMAN-SUBJECTS

Respiratory alkalosis (RA) is seen in diverse clinical conditions incl uding tissue hypoxia, malignancy, neurologic disorders, febrile states , pregnancy, and hepatic failure. Acute RA causes hypophosphaturia in rats, and this effect on renal phosphate handling is reversed by beta- adrenoreceptor antagonism. The objective of the present study was to d etermine the effect of acute RA on phosphate excretion in human patien ts in the absence and presence of beta-adrenoreceptor antagonism with propranolol. Twelve normal volunteers, 6 women and 6 men, were studied in two phases, once with placebo and once with intravenous infusion o f propranolol. In both groups, 30-minute renal clearances were taken d uring normoventilation (NV) and during acute RA induced by voluntary h yperventilation. Acute RA produced a significant decrease in plasma ph osphate (P-Pi) in the absence (Delta P-Pi = -0.16 +/- 0.03 mmol/L) and the presence (Delta P-Pi = -0.16 +/- 0.05 mmol/L) of propranolol. In the placebo group, fractional excretion of phosphate (FE(Pi)) decrease d from 24.1% +/- 3.4% in NV to 19.2% +/- 2.6% in RA. This was associat ed with a significant decrease in parathyroid hormone (P-PTH), from 3. 38 +/- 0.28 pmol/L in NV to 2.54 +/- 0.30 pmol/L in RA. In the propran olol group, FE(Pi) did not change significantly, from 19.1% +/- 2.7% i n NV to 18.7% +/- 3.0% in RA. This also occurred in the face of a decr ease in P-PTH, from 4.39 +/- 0.53 pmol/L in NV to 2.78 +/- 0.33 pmol/L in RA. Thus propranolol selectively changes the response of FE(Pi) to acute RA while leaving the P-Pi and P-PTH responses unaltered. This s uggests that beta-adrenoreceptors play a role in the regulation of the response of renal phosphate handling during acute RA and that this ro le involves a direct tubular effect on phosphate reabsorption, indepen dent of filtered load and hormonal status. We conclude that beta-adren oreceptor antagonism blunts the hypophosphaturic effect of acute respi ratory alkalosis in human subjects.