Dopamine enhances the phosphaturic effect of PTH during acute respiratory alkalosis.

The phosphaturic response to parathyroid hormone (PTH) is blunted during acute respiratory alkalosis. The objective of the present study was to determine the effect of dopamine on the blunted phosphaturic response to PTH during acute respiratory alkalosis. The phosphaturic response to PTH was determined in thyroparathyroidectomized (TPTX) normocapnic and respiratory alkalotic rats in the absence and presence of the infusion of exogenous dopamine (25 microg/kg/min) or of 3,4-dihydroxyphenylalanine (L-DOPA, 250 microg/kg/min) to increase endogenous dopamine synthesis. In normocapnic rats, PTH infusion (33 U/kg plus 1 U/kg/min) significantly increased the fractional excretion of phosphate (FE(Pi)), from 1.5%+/-0.5% to 28.4%+/-4.0%, (deltaFE(Pi) 26.9%+/-4.1%, n = 11, P<.05); in respiratory alkalotic rats, the increase was from 0.4%+/-0.1% to 11.4%+/-1.7% (deltaFE(Pi) 11.0%+/-1.8%, n = 13, P<.05). However, the phosphaturic response to PTH was attenuated in respiratory alkalotic rats (deltaFE(Pi) 26.9%+/-4.1% vs 11.0%+/-1.9%, P<.05). In normocapnic rats, in the presence of dopamine or L-DOPA infusions, PTH infusion significantly increased the FE(Pi) from 6.1%+/-2.3% to 33.4%+/-8.0% (deltaFE(Pi) 27.3%+/-7.0%, n = 5) and from 3.2%+/-0.6% to 32.5%+/-3.3% (deltaFE(Pi) 29.3%+/-3.2%, n = 7), respectively. In respiratory alkalotic rats, in the presence of dopamine infusion, PTH significantly increased the FE(Pi), from 0.6%+/-0.2% to 19.3%+/-3.3% (deltaFE(Pi) 18.7%+/-3.3%, n = 6); in the presence of L-DOPA infusion it increased from 1.0%+/-0.3% to 20.5%+/-2.8% (deltaFE(Pi) 19.5%+/-2.9%, n = 8, P<.05 as compared with PTH alone). Thus the phosphaturic effect of PTH that was attenuated in respiratory alkalotic rats was enhanced by stimulation of endogenous dopamine synthesis by the infusion of L-DOPA.

The effects of respiratory alkalosis and acidosis on net bicarbonate flux along the rat loop of Henle in vivo.

We have studied the effects of acute respiratory alkalosis (ARALK, hyperventilation) and acidosis (ARA, 8% CO2), chronic respiratory acidosis (CRA; 10% CO2 for 7-10 days), and subsequent recovery from CRA breathing air on loop of Henle (LOH) net bicarbonate flux (JHCO3) by in vivo tubule microperfusion in anesthetized rats. In ARALK blood, pH increased to 7.6, and blood bicarbonate concentration ([HCO3-]) decreased from 29 to 22 mM. Fractional urinary bicarbonate excretion (FEHCO3) increased threefold, but LOH JHCO3 was unchanged. In ARA, blood pH fell to 7.2, and blood [HCO3-] rose from 28 to 34 mM; FEHCO3 was reduced to < 0.1%, but LOH JHCO3 was unaltered. In CRA, blood pH fell to 7.2, and blood [HCO3-] increased to > 50 mM, whereas FEHCO3 decreased to < 0.1%. JHCO3 was reduced by approximately 30%. Bicarbonaturia occurred when CRA rats breathed air, yet LOH JHCO3 increased (by 30%) to normal. These results suggest that LOH JHCO3 is affected by the blood-to-tubule lumen [HCO3-] gradient and HCO3- backflux. When the usual perfusing solution at 20 nl/min was made HCO3- free, mean JHCO3 was -34.5 +/- 4.4 pmol/min compared with 210 +/- 28.1 pmol/min plus HCO3-. When a low-NaCl perfusate (to minimize net fluid absorption) containing mannitol and acetazolamide (2 x 10(-4) M, to abolish H(+)-dependent JHCO3) was used, JHCO3 was -112.8 +/- 5.6 pmol/min. Comparable values for JHCO3 at 10 nl/min were -35.9 +/- 5.8 and -72.5 +/- 8.8 pmol/min, respectively. These data indicate significant backflux of HCO3-along the LOH, which depends on the blood-to-lumen [HCO3-] gradient; in addition to any underlying changes in active acid-base transport mechanisms, HCO3- permeability and backflux are important determinants of LOH JHCO3 in vivo.

Propranolol blocks the hypophosphaturia of acute respiratory alkalosis in human subjects.

Respiratory alkalosis (RA) is seen in diverse clinical conditions including 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 determine the effect of acute RA on phosphate excretion in human patients 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 of propranolol. In both groups, 30-minute renal clearances were taken during normoventilation (NV) and during acute RA induced by voluntary hyperventilation. Acute RA produced a significant decrease in plasma phosphate (PPi) in the absence (deltaPPi = -0.16 +/- 0.03 mmol/L) and the presence (deltaPPi = -0.16 +/- 0.05 mmol/L) of propranolol. In the placebo group, fractional excretion of phosphate (FEPi) decreased from 24.1% +/- 3.4% in NV to 19.2% +/- 2.6% in RA. This was associated with a significant decrease in parathyroid hormone (PPTH), from 3.38 +/- 0.28 pmol/L in NV to 2.54 +/- 0.30 pmol/L in RA. In the propranolol group, FEPi did not change significantly, from 19.1% +/- 2.7% in NV to 18.7% +/- 3.0% in RA. This also occurred in the face of a decrease in PPTH, 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 FEPi to acute RA while leaving the PPi and PPTH responses unaltered. This suggests that beta-adrenoreceptors play a role in the regulation of the response of renal phosphate handling during acute RA and that this role involves a direct tubular effect on phosphate reabsorption, independent of filtered load and hormonal status. We conclude that beta-adrenoreceptor antagonism blunts the hypophosphaturic effect of acute respiratory alkalosis in human subjects.

Intermittent alkaline urine in a cat fed an acidifying diet.

Detection of alkaline urine traditionally sends an alert to the clinician to consider the presence of a urease-producing bacterial urinary tract infection, postprandial alkaline tide, or the ingestion of a diet that is nonacidifying. In the cat of this report, acid urine was produced while the cat was in the home environment, but alkaline urine was produced following the stress of a long trip to the veterinarian's office. Stress-induced respiratory alkalosis was highly suspected as the cause for the alkaline urine. If traditional causes for alkaline urine are not apparent for cats that produce alkaline urine at the veterinary clinic, we suggest that urinary pH be determined on samples collected in the home.

Effects of systemic alkalosis on urinary magnesium excretion in the rat.

Metabolic alkalosis has previously been shown to have an antimagnesiuric influence. To further clarify this phenomenon, short-term clearance studies were performed on intact anesthetized rats subjected to 0.9% saline infusion, 0.15 M NaHCO3 infusion or acute respiratory alkalosis. The experimental protocols resulted in a similar degree of natriuresis in each of the three groups. The increase in plasma pH value was similar both in animals treated with NaHCO3 and animals with respiratory alkalosis. Filtered loads of Mg did not differ in the three experimental groups. However, only acute metabolic alkalosis was associated with a reduction in the absolute rate of Mg excretion (saline: 0.49 +/- 0.05 mu Eq/min; 0.15 M NaHCO3: 0.29 +/- 0.04 mu Eq/min; acute respiratory alkalosis: 0.48 +/- 0.03 mu Eq/min) and fractional Mg excretion (saline: 40.3 +/- 5.3%; 0.15 NaHCO3: 18.7 +/- 1.4%; acute respiratory alkalosis: 37.2 +/- 6.9%). A similar decrease in urinary Mg excretion in animals treated with bicarbonate infusion was observed following removal of the parathyroid gland. Moreover, for any given rate of urinary Na excretion, Mg excretion was lower in bicarbonate-treated animals than in rats infused with saline solution. Intact animals treated with increasing doses of NaHCO3 revealed a statistically significant inverse correlation between the Mg to Na clearance ratio and urinary and plasma bicarbonate concentration. In contrast, such a correlation was not observed during respiratory alkalosis. The findings suggest that bicarbonate ion directly stimulates tubular magnesium reabsorption independent of the presence or absence of parathyroid hormone.

Assessment of collecting tubule hydrogen ion secretion in acute respiratory alkalosis using the urinary pCO2.

The use of the urine-blood (U-B) pCO2 difference as a marker of collecting tubule H+ secretion (CTH+S) faces serious interpretative pitfalls when applied to animals with respiratory acidosis. The present study was aimed to examine the use of this parameter in rats with acute respiratory alkalosis. During infusion of sodium bicarbonate, the U-B pCO2 was only slightly lower in hypocapnic than in eucapnic rats (30 +/- 2.2 and 39 +/- 3.3 mmHg, p less than 0.05) and this difference was no longer significant when this parameter was examined as a function of urine bicarbonate concentration. In contrast, the increment in urine pCO2 elicited by bicarbonate loading (i.e. the delta pCO2) was markedly reduced in hypocapnic as compared to eucapnic rats (22 +/- 3.0 and 38 +/- 4.5 mmHg, respectively, p less than 0.01). The infusion of carbonic anhydrase while the urine was highly alkaline and the blood pCO2 kept constant resulted in a decrement in urine pCO2 which was less in hypocapnic than in eucapnic rats (-23.9 +/- 1.9 vs -33 +/- 2.8 mmHg, p less than 0.02). These findings indicate that pCO2 generation from CTH+S and titration of bicarbonate is reduced in hypocapnic rats. The data are in accord with our proposal that the delta pCO2 is a better index of CTH+S than the U-B pCO2 is the assessment of respiratory acid-base disorders.

Characterization of distal hydrogen ion secretion in acute respiratory alkalosis.

The effect of acute respiratory alkalosis (ARA) on distal nephron H+ secretion was evaluated by measuring urine-to-blood (U-B) Pco2 in dogs with highly alkaline urine (urine pH greater than 7.8). ARA led to a significant decrease in U-B Pco2 and in urine HCO3 concentration; urine pH, however, increased significantly, indicating that the decrease in urine Pco2 was of greater magnitude than the decrease in urine HCO3 concentration. For any given urine HCO3 concentration urine Pco2 was lower (i.e., urine pH was higher) in ARA than in controls. Administration of tris(hydroxymethyl)aminomethane (Tris) during ARA resulted in a significant increase in U-B Pco2 to control values. In animals with moderately alkaline urine (urine pH 6.4--7.4) and high urine PO4 concentration, ARA resulted in a significant decrease in UB-Pco2 and urine PO4 concentrations. Neutral PO4 infusion in these dogs resulted in an increase in urine PO4 concentration and U-B Pco2 to control levels. These data demonstrate that ARA results in a significant decrease in U-B Pco2 that is not solely attributable to changes in urine HCO3 concentration. The observation that Tris and PO4 infusion during ARA raises U-B Pco2 to control levels suggests that the ability to secrete H+ is intact.