Thyroparathyroidectomized Dogs Research Articles

Systemic and renal hemodynamic consequences of manipulation of serum calcium and/or parathyroid hormone in the intact conscious mongrel dog.

Studies were undertaken in conscious mongrel dogs to separate the systemic and renal hemodynamic effects of alterations in serum calcium (Ca) from those of parathyroid hormone (PTH) in an intact conscious animal. Blood pressure was measured intra-arterially, cardiac output was determined by dye-dilution or thermodilution, total peripheral resistance (TPR) was calculated from standard formulae, and renal hemodynamics were estimated by the clearance of inulin and para-aminohippurate. Measurements were made before and after a 2 hour calcium chloride (CaCl2) infusion in 10 dogs (group 1). These animals had previously received a dose of PTH to prevent suppression of PTH during the CaCl2 infusion. Ionized calcium (Ca++) and TPR increased significantly. Blood pressure increased but not significantly. Administration of EDTA did not significantly change any systemic hemodynamic variable in eight thyroparathyroidectomized dogs (group 2). Chelation in seven dogs with intact parathyroid glands (group 3) reduced mean arterial blood pressure and total peripheral resistance. Renal hemodynamic measurements were not affected. Isolated acute elevation of serum Ca++, independent of suppression of PTH, increased total peripheral resistance. Decreased serum Ca++ required normal activity of parathyroids to reduce total peripheral resistance. The renal circulation was resistant to acute manipulation of ionized serum calcium and PTH. CaCl2 infusion to intact dogs (group 1) decreased serum magnesium significantly, increased urine flow rate, and decreased urinary PGE2 excretion. Comparisons between group 2 and group 3 revealed a greater decline in serum Mg and urinary prostaglandin E2 excretion in group 2 vs group 3. Elevation of peripheral resistance due to acute Ca elevations was accompanied by decreased serum Mg and decreased renal prostaglandin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 1,25(OH)2D3 on the relative contributions of skeletal 45Ca and intestinal 40Ca to blood calcium in normal and thyroparathyroidectomized dogs

The effects of gradually increasing doses of 1,25(OH)2D3 on plasma calcium and 45Ca radioactivity were studied in young dogs that had been extensively prelabelled with 45Ca. The effects of orally and intravenously administered 1,25(OH)2D3 were evaluated in normal and thyroparathyroidectomized dogs fed a normal diet. In normal dogs when 1,25(OH)2D3 increased the plasma calcium within the normal range (2.9-3.1 mmol/L) there was no significant increase in plasma 45Ca. In thyroparathyroidectomized dogs, oral or intravenous 1,25(OH)2D3 increased the low blood calcium to a normal level (1.8-2.9 mmol/L) without significantly increasing plasma 45Ca. In normal and thyroparathyroidectomized dogs, any 1,25(OH)2D3-induced increase in plasma calcium above the normal range was associated with a significant increase in 45Ca, indicating mobilization of bone calcium. Intravenous administration of 1,25(OH)2D3 in the normal or thyroparathyroidectomized dogs had a much larger effect than oral doses in mobilizing bone 45Ca when inducing a similar level of hypercalcemia. The major physiological effect of 1,25(OH)2D3 in the low or normal range of plasma calcium is on intestinal absorption of calcium without a significant effect on mobilizing bone calcium. The pharmacological effect of 1,25(OH)2D3 in vivo is to mobilize bone calcium as well as dietary calcium into blood.

158 RENAL EFFECT OF PHYSIOLOGICAL AND PHARMACOLOGICAL DOSES OF HUMAN PTH, 1–34, IN MEN

Recent study of Puschett et al. (Mineral Electrolyte Metab. 6:190, 1981) showed that infusion of bovine PTH at physiological dose (0.3-0.5 u/kg) in thyroparathyroidectomized dogs produced phosphaturia and a reduction in urinary Ca excretion, but no increase in urinary excretion or renal tissue content of cAMP, suggesting that some effects of PTH may be mediated by mechanisms other than cAMP. In order to assess whether similar phenomena can be observed in human, we infused human PTH, 1-34, at 0.3 u/kg and 3 u/kg in 5 normal adults and measured urinary cAMP (UcAMP), %TRP, Ca, Mg, Na, K, and plasma cAMP (PcAMP) in the next 3 hours. As shown in the table, PTH at 0.3 u/kg induced phosphaturia of a similar magnitude and a comparable urinary excretion of electrolytes to that of 3 u/kg but PcAMP and UcAMP were markedly different. After 0.3 u/kg, there was no rise in PcAMP, and a small rise in UcAMP indicating a difference in handling and production of cAMP after physiological and pharmacological dose of PTH.

Effect of parathyroid hormone on the determinants of glomerular filtration in dogs

Elevated levels of parathyroid hormone (PTH) often are associated with reduced glomerular filtration rate (GFR) in humans. Although PTH has been reported to reduce the ultrafiltration coefficient (Kf) in rats, GFR declined only if they were plasma expanded. In contrast, PTH does not reduce GFR in dogs, despite filtration pressure disequilibrium. To evaluate this apparent discrepancy, the determinants of GFR were measured in acutely thyroparathyroidectomized dogs. In the absence (n = 8) and presence (n = 10) of synthetic bovine PTH, GFR was 29 +/- 3 and 26 +/- 2 ml/min; Single nephron glomerular filtration rate was 58 +/- 4 and 51 +/- 3 nl/min; glomerular plasma flow was 248 +/- 22 and 250 +/- 24 nl/min; glomerular capillary pressure was 58 +/- 2 and 61 +/- 3 mmHg; Bowman's space pressure was 19 +/- 2 and 19 +/- 1 mmHg; and systemic oncotic pressure was 19 +/- 0.8 and 18 +/- 0.5 mmHg. Average effective filtration pressure (EFP) was significantly greater in the presence (18.6 +/- 1.3 mmHg) than in the absence (14.6 +/- 0.9 mmHg) of PTH. Therefore, Kf per glomerulus calculated from these data was significantly (P less than 0.01) less in the presence than in the absence of PTH (2.91 +/- 0.29 and 3.98 +/- 0.16 nl X min-1 X mmHg-1, respectively). It is concluded that PTH reduced Kf. Whereas this effect predicts reduced GFR in dogs, given filtration pressure disequilibrium, a concomitant increase in EFP maintained GFR in the present study.

Glomerular filtration rate and plasma pH as determinants of phosphate reabsorption

Glomerular filtration rate (GFR) was altered by varying renal perfusion pressure in volume-expanded, anesthetized dogs infused with ethacrynic acid. Phosphate reabsorption varied linearly with GFR (r greater than 0.9), 0.83 of the increase in filtered load being reabsorbed. Phosphate reabsorption at comparable filtered loads was not significantly changed by raising plasma bicarbonate concentration from 30 to 55 mM and adjusting PCO2 to keep plasma pH constant. Plasma pH was altered by inducing hyper- and hypocapnia or infusing bicarbonate. Plasma phosphate concentration varied with plasma pH before phosphate infusion and was kept constant at 3.4 +/- 0.1 mM in intact and thyroparathyroidectomized dogs; some of which were also examined during hyperchloremic acidosis. At comparable GFR, phosphate and bicarbonate reabsorption correlated (r greater than 0.9), except during acidosis when the filtered load of bicarbonate became inadequate. In all experiments phosphate reabsorption and plasma pH correlated (r greater than 0.85). Compared with control values at plasma pH 7.4, phosphate reabsorption increased by about 40% during acidosis (pH 7.1) and decreased by about 50% during alkalosis (pH 7.8) both in intact and thyroparathyroidectomized dogs. We propose that net hydrogen ion secretion is the common determinant of phosphate and bicarbonate reabsorption.

Circadian variations in contributions of bone and intestine to plasma calcium in dogs.

Young euparathyroid dogs, prelabeled with radiocalcium and fed a normal-calcium diet exhibited circadian variations in the amount of bone calcium contributed to the plasma calcium pool, as evaluated by changes in plasma calcium-45 radioactivity. When these dogs were fed a low-calcium diet or fasted, the contribution of bone calcium to plasma calcium rose to the point where bone constituted nearly the sole source of plasma calcium, and plasma calcium-45 no longer varied. In thyroparathyroidectomized (TPTX) dogs fed a normal diet, the fraction of plasma calcium due to bone contribution was reduced and plasma calcium-45 did not vary. When dietary calcium in TPTX dogs was increased by supplementation with calcium lactate pills, total plasma calcium rose, but the contribution of bone calcium to the plasma calcium pool remained unchanged. Thus the ability of normal young dogs to modulate bone calcium mobilization in response to dietary calcium intake appears to be hormonally regulated in a circadian manner.

Effect of plasma calcium concentration on the metabolic clearance rate of calcitonin in the dog.

Plasma immunoreactive calcitonin (iCT) levels generally are not elevated in chronic, nonmalignant, hypercalcemic states. Normocalcitoninemia might occur despite increased CT secretion if hypercalcemia itself accelerated the clearance of CT from the circulation. Therefore, we have measured the metabolic clearance rate (MCR) of human CT (hCT), infused to constant plasma levels in thyroparathyroidectomized dogs, under conditions of acute and chronic hypo- and hypercalcemia. Acute increases of plasma calcium were without significant effect on the MCR of hCT, but chronic hypercalcemia, induced by dihydrotachysterol treatment, reduced the MCR of hCT by 30% (P less than 0.05) and glomerular filtration rate (GFR) by 40% (P less than 0.02). There was a significant, positive correlation (r = 0.60, P less than 0.02) between GFR and the MCR of CT. The data suggest that failure to detect elevated iCT levels in chronic hypercalcemia is not the result of an increased MCR of CT. In fact, hypercalcemia should exaggerate the effect of increased CT secretion by decreasing the renal clearance of the hormone.

Calcium (Ca) mediated phosphate (PO4) transport in the proximal convoluted tubule (PCT) of the rabbit.

Several clearance studies have suggested a direct effect of calcium (Ca) on phosphate (PO4) handling by the kidney. Micropuncture studies by Amiel and colleagues1 have shown enhancement of fractional phosphate reabsorption in the proximal convoluted tubule when plasma calcium was raised from low towards normal values in parathyroidectomized rats. Conversely, Goldfarb et al 2 have shown a decline in fractional phosphate reabsorption in this portion of the nephron with the induction of mild hypercalcemia in thyroparathyroidectomized dogs. The divergence of these results may be due to species differences, the level of plasma phosphate or ionized calcium before and after calcium chloride administration, or the other various indirect effects of calcium on phosphate handling by the nephron.

Metabolic alkalosis in models of primary and secondary hyperparathyroid states.

Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal tubular calcium transport: effects of changes in filtered calcium load.

Micropuncture experiments were performed in thyroparathyroidectomized dogs to examine the influence of changes in filtered calcium load on segmental tubular calcium reabsorption. Filtered calcium load was changed either by reducing glomerular filtration rate (GFR) by aortic clamping (group I) or by progressive calcium infusion (group II) to increase plasma ultrafilterable calcium concentration (UFCa). The results suggest that fractional proximal calcium reabsorption responds similarly to altered filtered load, whether produced by changes in GFR or UFCa. In contrast, fractional reabsorption by the loop segment is progressively reduced as UFCa is increased but is relatively unchanged by alterations in filtered load secondary to altered GFR. These data indicate a specific parathyroid hormone-independent reciprocal effect of UFCa on calcium reabsorption in the loop segment, which may be an important determinant of urinary calcium excretion.

Canine renal receptors for parathyroid hormone. Down-regulation in vivo by exogenous parathyroid hormone.

Chronic elevation of circulating parathyroid hormone (PTH) is associated with decreased target cell responsiveness to PTH. To study the subcellular mechanism of this phenomenon we evaluated PTH receptors and adenylate cyclase activity in renal cortical membranes prepared before and after infusion of bovine parathyroid gland extract (PTE) into thyroparathyroidectomized dogs. PTE infusion resulted in a 53% decrease in the number of high-affinity receptors (P less than 0.01) associated with a 66% decrease in PTH-stimulated adenylate cyclase (P less than 0.01) relative to paired base-line values. Both the equilibrium constant of dissociation (KD) for PTH binding and the concentration of PTH that caused half-maximal stimulation of adenylate cyclase were in the range of 1 to 4 nM, and were unaffected by the PTE infusion. Responsiveness of the renal adenylate cyclase to sodium fluoride was 88% of base-line values. Infusion of the PTE vehicle alone did not affect PTH receptor number or blunt the adenylate cyclase response to PTH. Pretreatment of the membranes made after PTE infusion with guanosine triphosphate (GTP), which is known to produce dissociation of receptor-bound PTH, failed to restore either receptor number or PTH-stimulated adenylate cyclase. This finding was not due to a lack of efficacy of the GTP pretreatment, because identical GTP pretreatment restored PTH binding to base-line values in membranes partially occupied by incubation with PTH in vitro. Thus, simple residual occupancy of PTH receptors by the infused hormone did not appear to account for the observed receptor loss. The results of this study suggest that target cell resistance to PTH in patients with hyperparathyroidism might occur, at least in part, due to down-regulation of PTH receptors by circulating hormone.

Metabolic acidosis and parathyroidectomy increase Na+-H+ exchange in brush border vesicles.

Na+-H+ exchange across the brush border membrane of the renal proximal tubular cell is a mechanism for Na+ reabsorption and H+ secretion. An electroneutral Na+-H+ exchange activity has been identified in isolated renal brush border membrane vesicles from rat and dog kidney, and increased Na+-H+ exchange has been measured in brush border membrane vesicles from remnant kidneys of dogs with chronic renal failure. To ascertain whether changes in H+ secretion by the kidney observed in chronic metabolic acidosis and in states of altered parathyroid function might result from altered Na+-H+ exchange across the renal cortical cellular brush border membrane, we measured Na+-H+ exchange in brush border membrane vesicles from kidneys of dogs with chronic metabolic acidosis and from kidneys of thyroparathyroidectomized dogs. Increased amiloride-sensitive Na+-H+ exchange was demonstrated in brush border membrane vesicles from kidneys of both groups of dogs, suggesting that adaptations in H+ excretion in chronic metabolic acidosis and hypoparathyroidism might be explained by increased activity of a renal brush border membrane Na+-H+ exchanger.

Parathyroid hormone: effects of the 3-34 fragment in vivo and vitro.

The biologically active fragment ofparathyroid hormone, consisting of residues 1-34, and its in vitro antagonist, fragment 3-34, were administered separately or in combination to chronically thyroparathyroidectomized dogs. These fragments were also studied in vitro with dog renal cortical membranes. Fragment 3-34 inhibited the stimulation of adenylate cyclase by fragment 1-34 in vitro, but had no agonist or antagonistic effects on renal phosphate transport in vivo.

Parathyroid hormone-independent adaptation of the renal handling of phosphate in response to renal mass reduction

In man as well as in experimental animals progressive renal failure is associated with a decrease in the fractional reabsorption (FR) of inorganic phosphate (Pi). This response has been considered as an adaptation phenomenon and generally attributed to an increase in parathyroid hormone (PTH) secretion. One report indicates that in chronic thyroparathyroidectomized (TPTX) dogs treated with large doses of vitamin D progressive renal failure can also be associated with a fall in FRPi. However, in this latter study the concomittant administration of vitamin D could have accounted for the observed decrease in FRPi. In our study we investigated whether or not chronic reduction in renal mass leads to a similar decrease in maximal net tubular Pi reabsorption per volume of glomerular filtrate (maximal TRPi/ml GF) in the presence and absence of PTH and without pharmacological supplementation in vitamin D. Male rats were either TPTX or sham-operated (intact). One and two weeks later the animals of both groups were either subtotally nephrectomized (NX) in two stages or sham-operated (control). Four weeks after the second renal operation, the glomerular filtration rate (GFR) and the reabsorption of Pi were determined by clearance methodology under acute sodium chloride and Pi infusion, that is, at endogenous and increased plasma Pi concentrations ([Pi]Pl.). Thus maximal TRPi/ml GFR could be determined. In rats with intact parathyroid glands GFR was 1.56 +/- 0.10 (mean +/- SEM) and 0.54 +/- 0.10 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 2.24 +/- 0.07 in control and 1.57 +/- 0.18 mumol/ml (P less than 0.005) in NX. In TPTX rats GFR was 1.66 +/- 0.27 and 0.62 +/- 0.06 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 3.80 +/- 0.20 in control and 2.95 +/- 0.13 mumol/ml (P less than 0.005) in NX. The marked decrease in maximal TRPi/ml GF observed in TPTX after subtotal NX could not be ascribed to any consistent change in plasma calcium. Our study provides conclusive evidence that the decrease in maximal TRPi/ml GF in response to renal mass reduction can occur to the same degree in the presence or absence of PTH.

Modulation of parathyroid hormone-sensitive adenylate cyclase and arginine vasopressin-sensitive adenylate cyclase by calcium and GTP

Arginine vasopressin (AVP)- and parathyroid hormone (PTH)-sensitive adenylate cyclase were studied in the renal tissue of thyroparathyroidectomized dogs. The results indicate that AVP-sensitive adenylate cyclase activity was highest in the inner medulla followed by the middle medulla, outer medulla, and cortex, in declining order. In contrast, PTH-sensitive adenylate cyclase was absent in the inner medulla, and the highest stimulation was found in the cortex with lesser activity in outer and middle medulla. When 1 m m EGTA was included in the incubation mixture, the addition of both AVP- and PTH to the middle medullary homogenate resulted in additive responses suggesting two separate receptors for each hormone. This EGTA-induced additive effect was eliminated by the addition of calcium into the system, indicating that calcium concentration may be critical in modulating the interaction of AVP and PTH-sensitive adenylate cyclase. In contrast to some previous reports, a particulate fraction prepared from the middle medullary tissue was completely insensitive to either AVP or PTH. Hormonal sensitivity was restored by the addition of GTP or the supernatant.

Regulation of canine renal vesicle P i transport by growth hormone and parathyroid hormone

Renal phosphate (P i) reabsorption is increased by growth hormone (GH) and decreased by parathyroid hormone (PTH). Na +-stimulated P i transport across the brush border membrane of the proximal tubule is the initial step in the process of P i reabsorption. To determine whether changes in P i reabsorption induced by GH or PTH are accompanied by changes in brush border membrane Na +-gradient-stimulated P i transport, we examined the effect of in vivo GH and PTH administration and thyroparathyroidectomy on P i transport by isolated brush border membrane vesicles prepared from canine kidney. In experiments in which the effect of PTH administration was examined, the same animal provided the control kidney (before PTH administration) and the experimental kidney (after PTH administration). The Na +-gradient P i overshoot in vesicles isolated from normal, GH-treated and thyroparathyroidectomized dogs was increased after in vivo PTH administration. GH administration and thyroparathyroidectomy increased the height of the overshoot compared to normal. PTH administration decreased the apparent V value by 44% in vesicles from normal animals. The apparent V value was increased, compared to normal, by GH (34%) and thyroparathyroidectomy (57%). PTH administration decreased the apparent V in both the latter groups. GH administration to thyroparathyroidectomized dogs further increased the apparent V. Changes in the apparent V paralleled changes in P i reabsorption in vivo induced by experimental manipulations. We conclude that changes in renal P i reabsorption induced by GH were like those induced by PTH, accompanied by changes in the Na +-stimulated P i transport system in the renal brush border membrane, and that the effect of PTH on vesicular P i transport in GH-treated dogs did not differ from the effect on vesicles from normal animals.

Effects of calcium on a parathyroid hormone-sensitive adenylate cyclase inhibitor

Inhibition of parathyroid hormone (PTH)-sensitive adenylate cyclase by {Nle-8, Nle-18, Tyr-34} bPTH-(3–34) amide was studied in thyroparathyroid-ectomized dogs. The inhibitory effect was shown to be markedly enhanced by the addition of calcium ions into the in , vitro assay system. At 0.1 mM Ca 2+, complete inhibition by the antagonist was obtained. Chelation of exogenous Ca 2+ by EGTA eliminated the Ca 2+-induced inhibition. Both the basal and hormone-stimulated activities were decreased in the presence of 0.1 mM Ca 2+, whereas the addition of EGTA increased both activities. Our results suggest that Ca 2+ modulates canine renal PTH-sensitive adenylate cyclase and its inhibition by substituted bPTH-(3–34).

Dissociative effects of piretanide on proximal tubular PO4 and HCO3 transport.

The effect of piretanide on renal electrolyte transport was evaluated by simultaneous micropuncture and clearance studies. In chronically thyroparathyroidectomized (TPTX) dogs, the drug caused an increased percentage excretion (%E) of sodium (from 0.6 +/- 0.1 to 15.2 +/= 1.8%, P less than 0.01) as well as of calcium (from 1.0 +/- 0.2 to 17.8 +/- 1.7%, P less than 0.001) and bicarbonate (from 1.2 +/- 0.4 to 5.9 +/- 0.9, P less than 0.001), but there was no change in %E of phosphate (4.0 +/- 0.9 to 6.6 +/- 1.6, P less than 0.10). In the presence of a constant infusion of parathyroid hormone (PTH) the drug caused a greater degree of natriuresis, calciuria, and bicarbonaturia and a significant increase in %E of PO4 (from 7.4 +/- 1.6 to 20.0 +/- 2.1, P less than 0.05). Proximal fractional reabsorption (PFR) of PO4 was unaffected, but there was a significant decrease in PFR of sodium, calcium, and bicarbonate in the TPTX dogs. The presence of PTH did not alter the effects of piretanide on PFR of phosphate and bicarbonate. There was no change in urinary or tubular fluid pH in either group of dogs. These data indicate that piretanide dissociates proximal PO4 transport from that of sodium and bicarbonate. In the presence of PTH, the drug inhibits PO4 transport beyond the late proximal convoluted tubule. In addition, tubular (and urinary) pH appears to be an important regulator of PO4 transport, especially in the absence of PTH.

Mechanism of the phosphaturia due to chlorothiazide.

CTZ caused a phosphaturia when baseline phosphate excretion was not already high. Furthermore, when th influence of PTH is withdrawn, the excretion of phosphate appears to be largely affected by changes in urinary pH.

Interaction of somatostatin with PTH and AVP: renal effects.

Six conscious intact dogs were studied to evaluate the interactions of somatostatin (SRIF) with exogenous antidiuretic hormone arginine vasopressin (AVP). SRIF administration caused a significant increase in free water clearance compared to a vehicle-treated group: -0.91 (+/- 0.41 SD) ml/min to 0.21 (+/- 0.32 SD) ml/min in the experimental group (P less than 0.01) versus 0.21 (+/- 0.81 SD) ml/min to -0.21 (+/- 0.68 SD) ml/min in the control (P greater than 0.5). Six conscious, thyroparathyroidectomized dogs were studied to test the interaction of SRIF and parathyroid extract (PTE). There were no significant changes in the phosphaturic and hypocalciuric effects of PTE with SRIF administration. We conclude that acute systemic SRIF administration interferes with the antidiuretic action of AVP, probably at the renal-tubular level, but does not antagonize the renal actions of PTE.