Significant Antidiuresis Research Articles

Acetazolamide: an improved treatment for lithium‐induced NDI? (LB726)

Lithium causes nephrogenic diabetes insipidus (Li‐NDI) and hydrochlorothiazide (HCTZ) forms, together with amiloride, the mainstay treatment for Li‐NDI patients. Earlier, we found that HCTZ, primarily known for inhibiting the NaCl‐co‐transporter (NCC), also reduces Li‐NDI in NCC knockout mice, coinciding with alkalinized urine, suggesting that inhibition of carbonic anhydrase (CA) by HCTZ plays a role. To test whether CA inhibition is a useful alternative therapy in Li‐NDI, the effect of acetazolamide (ACZ) was tested.Polarized mouse cortical collecting duct (mpkCCD) cells and mice were used to study the effect of ACZ on Li‐NDI.Treatment of mpkCCD cells with ACZ attenuated AQP2 downregulation by lithium. ACZ did, in contrast to amiloride, not affect transcellular voltage. Treatment of Li‐NDI mice with ACZ revealed a significant antidiuresis and increased urine osmolality, which was indifferent from Li‐NDI mice treated with HCTZ/amiloride. However, unlike HCTZ/amiloride, ACZ treatment did not result in hyponatremia, hyperkalemia, hypercalcaemia and metabolic acidosis. Moreover, ACZ rescued AQP2 expression over the entire length of the collecting duct, whereas HCTZ/amiloride only increased AQP2 levels in the renal papilla.In conclusion, our data reveal that ACZ attenuates lithium‐induced downregulation of AQP2 and NDI development. Moreover, as ACZ caused fewer side effects than the conventional treatment, ACZ may represent a better therapeutic agent than HCTZ/amiloride to treat Li‐NDI.Grant Funding Source: Supported by a VICI grant, a RUNMC grant and a grant from the Society of Experimental Laboratory Medicine.

Antidiuretic action of angiotensin II in the river lamprey Lampetra fluviatilis: evidence for endocrine control of kidney function in cyclostomes

Intravenous infusion of angiotensin II ([Asn¹ Val⁵]-Ang II) at 10⁻⁹ mol min⁻¹ kg⁻¹ body mass produced a significant antidiuresis in river lamprey Lampetra fluviatilis, captured during upstream migration and maintained in fresh water. Although the renin-angiotensin hormonal system (RAS) is now recognized in jawless fishes, until this study, the role of homologous Ang II in L. fluviatilis kidney function had not been examined. This study provides the first evidence for an antidiuretic action of Ang II in cyclostomes and, in evolutionary terms, suggests a renal function for the RAS in early vertebrates.

Desmopressin Resistant Nocturnal Polyuria May Benefit From Furosemide Therapy Administered in the Morning

There is increasing evidence that a subgroup of patients with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin may have an abnormal circadian rhythm of renal tubular sodium handling. The pathogenesis of this phenomenon remains to be elucidated. If the increased sodium excretion overnight results in desmopressin resistance, decreasing the sodium excretion overnight may result in subsequently better desmopressin response. We conducted a pilot study of the anti-enuretic and antidiuretic effects of desmopressin combined with 0.5 mg/kg furosemide daily in patients with desmopressin resistant nocturnal polyuria despite dietary sodium and protein restriction. Values were plotted against the reference frame of a desmopressin responsive enuresis group. Baseline values revealed significantly lower urinary osmolality and higher diuresis rate overnight compared to the reference population (monosymptomatic nocturnal enuresis desmopressin responders). Introduction of desmopressin resulted in normalization of nocturnal urinary osmolality. However, nocturnal polyuria persisted, despite reaching maximal urinary concentration overnight. Although protein and sodium restriction resulted in a significant decrease in urinary osmolality and diuresis rate, the difference was not clinically important enough to reach normal values or to achieve continence. Furosemide in the morning resulted in a significant increase in diuresis and osmotic and sodium excretion during the day, and decreased nighttime diuresis and osmotic excretion. In 9 of 12 patients the nocturnal antidiuretic effect resulted in an anti-enuretic effect, defined as enuresis less than 1 wet night per month. In 3 patients insufficient anti-enuretic effects were obtained despite significant antidiuresis. This pilot study clearly demonstrates that introduction of early morning furosemide results in a significantly lower nocturnal diuresis rate. Reduced diuresis associated with unchanged urinary osmolality results in decreased nocturnal osmotic excretion in compensation for increased osmotic (sodium) excretion during the daytime.

Glomerular Effects of AVT on the In Situ Perfused Trunk Preparation of the Dogfish

The effects of arginine vasotocin on the pattern of glomerular perfusion in an elasmobranch fish were examined using an in situ perfused renal trunk preparation. A significant antidiuresis was coupled with a marked reduction in the proportion of filtering glomeruli (86%-25%) and an increase in the proportion of perfused but not filtering (10%-53%) and non-perfused glomeruli (4%-22%). However, the reduction in filtering glomeruli was greater than predicted by measurements of urine flow rate and glomerular filtration rate alone, suggesting that alterations in single nephron glomerular filtration rate may occur.

Diuretic and antidiuretic diuretic of the leaf extracts ofVernonia cinerea (Less) (Fam. Compositae)

The diuretic and anti-diuretic potency of the leaf extracts of Vernonia cinerea was studied in albino rats. The chloroform extract of the leaf induced significant diuresis, while the methanol and aqueous extracts induced significant antidiuresis in rats. In both cases, the observed effects on urine volume and electrolyte excretion were dose dependent. The trend was a significant increase (in the case of diuresis) in natriuretic and kaliuretic activity and a significant decrease (in the case of antidiuresis) in natriuresis and kaliuresis. © 1997 John Wiley & Sons, Ltd.

Bradykinin B 2 Receptor Modulates Renal Prostaglandin E 2 and Nitric Oxide

Bradykinin and lys-bradykinin generated intrarenally appear to be important renal paracrine hormones. However, the renal effects of endogenously generated bradykinin are still not clearly defined. In this study, we measured acute changes in renal excretory and hemodynamic functions and renal cortical interstitial fluid levels of bradykinin, prostaglandin E 2 , and cGMP in response to an acute intrarenal arterial infusion of the bradykinin B 2 receptor antagonist Hoe 140 (icatibant), cyclooxygenase inhibitor indomethacin, or nitric oxide synthase inhibitor N G -monomethyl- l -arginine (L-NMMA) given individually or combined in uninephrectomized, conscious dogs (n=10) in low sodium balance. Icatibant caused a significant decrease in urine flow, urinary sodium excretion, and renal plasma flow rate (each P <.001). Glomerular filtration rate did not change during icatibant administration. Icatibant produced an unexpected large increase in renal interstitial fluid bradykinin ( P <.0001) while decreasing renal interstitial fluid prostaglandin E 2 and cGMP (each P <.001). Both indomethacin and L-NMMA when given individually caused significant antidiuresis and antinatriuresis and decreased renal blood flow (each P <.001). Glomerular filtration rate decreased during L-NMMA administration ( P <.001) and did not change during indomethacin administration. Combined administration of icatibant and indomethacin or L-NMMA caused significant decreases in renal excretory and hemodynamic functions, which were not different from changes observed with icatibant alone. The failure of icatibant to change renal function after inhibition of cyclooxygenase and nitric oxide synthase activity suggests that the effects of kinin B 2 receptor are mediated by intrarenal prostaglandin E 2 and nitric oxide generation. The increase in renal interstitial fluid bradykinin during icatibant requires further study of possible alterations in kinin synthesis, degradation, or clearance as a result of B 2 receptor blockade.

The antidiuretic effect of pneumadin requires a functional arginine vasopressin system

Pneumadin is an antidiuretic decapeptide, recently isolated from rat and human lung. Bolus intravenous injection of 5 nmol of pneumadin into water-loaded rats caused a rapid and significant antidiuresis and a reduction in Na + and Cl − excretion. Pneumadin administration did not alter mean arterial pressure, right atrial pressure, heart rate or haematocrit. Bolus intravenous injection of 20 nmol of pneumadin into non-water-loaded rats caused a significant increase in arginine vasopressin (AVP) within 10 min. Pneumadin administration also increased circulating atrial natriuretic peptide (ANP) but did not alter aldosterone or plasma renin activity levels. Injection of pneumadin into water-loaded Brattleboro rats, which genetically lack circulating AVP, did not change urine flow, confirming that the pneumadin induced antidiuresis is AVP dependent. Radioactive pneumadin was cleared from the circulation with a t 1 2 β of 480.3 s. Radioactive pneumadin, isolated from plasma, eluted at an altered position on reverse phase HPLC, which indicated that the peptide was modified in vivo. This modification was also observed when synthetic pneumadin was incubated in rat plasma in vitro. Purification and sequencing of the modified synthetic peptide indicated that the modification is not a proteolytic cleavage. These results indicate that pneumadin injected into the rat caused an antidiuresis by altering circulating AVP levels.

Evidence that intrarenal bradykinin plays a role in regulation of renal function.

Bradykinin (BK) is produced by the kidney, but the role of the renal kallikrein-kinin system (KKS) in the control of renal function is not understood. We studied the effects of intrarenal infusion of the BK antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid (BKA, n = 5) and BK (n = 4) alone or combined with antagonist (BKA 0.025 ng.kg-1 x min-1 + BK 0.25 ng.kg-1 x min-1, n = 4) in uninephrectomized conscious dogs in sodium balance at 10 and 80 meq/day. During low sodium intake, administration of BKA (infusions from 0.025 to 2.5 ng.kg-1 x min-1) caused a significant antidiuresis (P < 0.0001) and antinatriuresis (P < 0.0001) and a decrease in fractional sodium excretion (P < 0.0001). There were no changes in estimated renal plasma flow (RPF) or glomerular filtration rate during intrarenal administration of BKA at 0.025 and 0.25 ng.kg-1 x min-1. A dose of 2.5 ng.kg-1 x min-1 BKA caused a significant decrease in RPF. There were no changes in plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure during intrarenal BKA administration. At 80 meq/day sodium balance (n = 5), intrarenal administration of BKA did not cause any systemic or renal effects. Intrarenal administration of BK at 0.25 ng.kg-1 x min-1 during low sodium balance caused an increase in urine flow rate and urinary sodium excretion. Coinfusion of BK with BKA completely abrogated the renal excretory changes induced by BKA. These data suggest that intrarenal KKS plays a role in control of renal function largely by a tubular mechanism during low sodium intake.

Intrarenal DA2 dopamine receptor stimulation in the conscious dog.

DA2 dopamine receptors are present in renal blood vessels and glomeruli. Stimulation of DA1 dopamine receptors leads to renal vasodilation, diuresis, and natriuresis, but a functional role for renal DA2 receptors is largely unknown. We investigated the possible role of DA2 receptors in the control of renal function by intrarenal infusion of a highly specific DA2 agonist, LY 171555 (LY), in conscious uninephrectomized dogs (n = 5) in metabolic balance at sodium intake of 40 meq/day. The infusion of LY at 0.5 pmol.kg-1.min-1 did not change the urinary sodium excretion or renal hemodynamic function. A significant dose-dependent antidiuresis (F = 8.1, P less than 0.0001) and antinatriuresis (F = 93.3, P less than 0.0001) and a decrease in filtration fraction (F = 2.3, P less than 0.02) occurred as the LY dose was increased from 1.0 to 10.0 pmol.kg-1.min-1. There were no changes in systemic plasma renin activity, plasma aldosterone concentration, or mean arterial pressure during intrarenal LY administration. These data suggest that intrarenal DA2 receptor stimulation with LY decreases renal sodium excretion in part by hemodynamic mechanisms. Renal dopamine may act at vascular and/or glomerular DA2 receptors to modulate renal function.

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0 +/- 0.25 vs 2.4 +/- 0.2 ng AngI/ml/h; p less than 0.01) and glucagon levels (40 +/- 11 vs 20 +/- 16 pg/ml; p less than 0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE2, and PGF2 alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r = 0.7; p less than 0.001) and urinary prostaglandin E2 and glomerular filtration (r = 0.52; p less than 0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.

Evidence that intrarenal dopamine acts as a paracrine substance at the renal tubule

Dopamine is synthesized within the kidney and dopamine 1 (DA1) receptors are associated with the proximal tubule. In pharmacological doses, dopamine increases renal blood flow and sodium excretion. It is possible that dopamine formed intrarenally acts locally via renal dopamine receptors to control renal function. We investigated the possible paracrine action of renal dopamine by intrarenal administration of a specific DA1 antagonist, Sch 23390, in doses confined to the kidney in conscious uninephrectomized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Changes (mean +/- SE) in renal excretory and hemodynamic function in response to cumulative infusions of several doses of Sch 23390 (0.01, 0.1, 1.0, 5.0, and 10.0 pmol.kg-1.min-1) were studied. Sch 23390 at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or sodium excretion. Sch 23390 in doses from 0.1 to 10.0 mol.kg-1.min-1 caused a significant dose-dependent antidiuresis (F = 44.9, P less than 0.0001) and antinatriuresis (F = 42.1, P less than 0.0001) and a decrease in fractional sodium excretion (F = 44.2, P less than 0.0001). No changes in estimated renal plasma flow, glomerular filtration rate, plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure occurred with any dose of intrarenal Sch 23390 infused into the renal artery. Rebound diuresis and natriuresis occurred after cessation of the DA1 blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II modulates the intrarenal effects of atrial natriuretic peptide.

The mechanism by which atrial natriuretic peptide (ANP) increases renal water and solute excretion is not fully understood. We studied the renal effects of ANP and angiotensin II (ANG II) separately and together in uninephrectomized conscious dogs (n = 7) in sodium metabolic balance (80 meq/day). Exogenous ANG II and ANP were without measurable systemic effects as demonstrated by absence of changes in blood pressure, plasma aldosterone concentration, and plasma renin activity. The quantity of ANG II that had significant renal effects that were without measurable systemic effects was 0.2 pmol.kg-1.min-1. Three infusion rates of ANP had significant renal effects (1, 10, and 20 pmol.kg-1.min-1). These quantities of ANP caused significant diuresis, natriuresis, kaliuresis, and increased glomerular filtration rate without significant changes in renal plasma flow. ANG II alone caused significant antidiuresis, antinatriuresis, and decreased glomerular filtration rate and renal plasma flow. When ANG II and ANP were given together, no change in urinary flow rate, urinary sodium or potassium excretion, or renal plasma flow was observed, whereas glomerular filtration rate increased. Filtration fraction increased significantly with ANG II and ANP separately and together. Intrarenal ANP prevents the ANG II-induced decrement in urinary sodium excretion and urine flow rate. ANP may play an important role in escape from the sodium-retaining action of intrarenal ANG II.

Intrarenal effects of [Ala-Pro-Gly-(Ile3-Val5)] angiotensin II in the conscious dog.

Amphibian skin has functional characteristics of epithelium in the mammalian distal nephron and plays an important role in sodium and water metabolism in these animals. A peptide extracted from the skin of the Australian frog Crinia georgiana has been purified, has been determined to have the amino acid sequence of [Ala-Pro-Gly-(Ile3-Val5)]angiotensin II, and recently has been synthesized. We studied the renal effect of synthetic frog skin angiotensin II (FSAII) infused via the renal artery in doses that were confined to the kidney. FSAII was infused intrarenally at 0.2, 2, and 4 pmol/kg.min in uninephrectomized conscious dogs (n = 5) in metabolic balance at a sodium intake of 80 meq/day. FSAII was confined to the kidney, as demonstrated by the absence of any systemic pressor response and/or any increase in plasma aldosterone concentrations during intrarenal FSAII infusion at rats of 0.2 and 2 pmol/kg.min. At 4 pmol/kg.min, FSAII traversed the kidney in amounts sufficient to stimulate aldosterone secretion (P less than 0.05). All three doses of FSAII caused significant antidiuresis and antinatriuresis, and decreased fractional excretion of sodium. There were no changes in the glomerular filtration rate (GFR) or renal plasma flow (RPF) during FSAII infusion at 0.2 and 2 pmol/kg.min. At 4 pmol/kg.min, FSAII engendered a significant decrease in GFR and RPF, while the filtration fraction increased. There were no significant changes in arterial blood pressure at any dose of FSAII. When confined to the kidney, FSAII caused antidiuresis and anti-natriuresis in the absence of a change in GFR and RPF. These results provide evidence that angiotensin acts directly at the renal tubular level to alter renal function.

Renal sensitivity to angiotensin II in the conscious dog.

Local formation of angiotensin II (AII) within the kidney has been demonstrated. Changes in renal function induced by inhibitors of the renin-angiotensin system have been the basis for the postulate that AII may act as a paracrine substance in the kidney. We studied the renal action of chronic intrarenal infusions of AII at doses between 2 and 2000 fmol/kg X min in uninephrectomized conscious dogs monitored on 80 meq daily sodium intake. Exogenous AII was confined to the kidney, as demonstrated by the absence of systemic pressor and adrenal cortical responses during the intrarenal infusion. After 2 control days, each dose of AII was infused intrarenally for a period of 3 days. The smallest intrarenal dose of AII that caused significant antinatriuresis and antidiuresis was 20 fmol/kg X min. A significant reduction in urinary volume and sodium excretion occurred during the first 24 h of the infusion period and was proportionate to the amount of peptide infused. Renal escape from the antinatriuretic and antidiuretic effects of the peptide ensued on the second and third days of infusion. There were no significant changes in urinary potassium excretion, plasma renin activity (PRA), plasma aldosterone concentration, or blood pressure throughout the period of intrarenal AII administration. These data demonstrate dose-dependent direct antinatriuretic and antidiuretic actions of low AII concentrations. Escape from the sodium-retaining action of intrarenal AII occurred by 48 h and was independent of suppression of endogenous renin-angiotensin. These results indicate that AII alters renal function by direct intrarenal mechanisms.

Effects of Intravenous Aspirin on Prostaglandin Synthesis and Kidney Function in Intensive Care Patients

The effects of intravenous acetylsalicylic acid (1.0 g bolus) on renal function and prostaglandin synthesis were evaluated in a prospective, controlled study in eight patients in an intensive care unit. Four of these patients had congestive heart failure. Administration of acetylsalicylic acid caused significant antidiuresis (-56%), antinatriuresis (-82%), renin suppression (-26%) and decreased GFR (-41%). All of these changes were completely reversible within 1-2 hours and tended to be more pronounced in the patients with congestive heart failure. Urinary excretion of prostaglandin E2 was depressed profoundly (-93%) and did not return to more than 45% of control 6 h after the administration of acetylsalicylic acid. We conclude that intravenous acetylsalicylic acid affects kidney function in a manner similar to other prostaglandin synthesis inhibitors. Its effects are, however, short-lived. The inhibition of urinary PGE2 excretion outlasts GFR depression, antidiuresis, antinatriuresis and renin suppression by several hours.

Head-up tilt in the nonhuman primate. Effects of renal denervation.

Experiments were performed to determine the role of the renal nerves in mediating the antinatriuresis of head-up tilt in the nonhuman primate. Male Macaca fascicularis monkeys underwent chronic bilateral renal denervation or sham surgery and were allowed a 1- to 2-week recovery period. After that time, each animal was anesthetized with sodium pentobarbital and subjected to 40 min of 35 degrees head-up tilt. Renal perfusion pressure was maintained constant throughout the experiment. Tilt caused significant decreases in urine flow, sodium excretion and osmolar clearance and increases in urine osmolality in both groups. Creatinine and para-aminohippurate clearances decreased in the sham-operated animals but were unchanged in the denervated animals. Although the pattern of the renal excretory responses showed some group differences in that a significant antidiuresis and antinatriuresis occurred after 10 min of tilt in the sham-operated group but not until 20 min in the denervated group, the magnitudes of these excretory responses were similar in both groups throughout the entire tilt procedure. These results suggest that, in this species, the renal nerves are not necessary for eliciting the overall antinatriuretic response to orthostasis but may have some minor involvement in the onset of the response.

Patterns of cloacal water and electrolyte excretion in constantly-loaded intact and colostomized ducks ( Anas platyrhynchos)

1. 1. The patterns of cloacal water and electrolyte excretion were qualitatively similar in intact and chronically colostomized ducks given oral loads of either distilled water or electrolyle solution. 2. 2. The rates of Na + and K + excretion were each selectively increased in birds loaded with solutions containing a relatively higher concentration of each ion. 3. 3. Compared to the intact birds, the colostomized birds showed lower rates of electrolyte excretion following administration of identical electrolyte loads and thus appeared to be retaining electrolyte. 4. 4. At the same time. a significant antidiuresis of similar magnitude occurred in each group of saline-loaded birds. 5. 5. The possible contributions of renal and post-renal mechanisms to the overall conservation of water in intact and colostomized ducks are discussed.

Mechanisms of renal dysfunction during positive end-expiratory pressure ventilation

Twenty-seven anesthetized dogs were studied to determine the effects of intrarenal blood flow distribution, hepatic congestion, and cardiac output (Q) and/or intravascular volume on renal function during ventilation with positive end-expiratory pressure (PEEP) of 10 cmH2O. In 10 dogs intrarenal blood flow distribution, as determined by the radioactive-microsphere technique, remained unchanged although PEEP caused a significant antidiuresis and antinatriuresis. The selective release of hepatic congestion during PEEP in eight animals by means of a vena cava to jugular venous shunt circuit did not restore renal function. Nine dogs were transfused with 25 ml/kg of autologous blood during PEEP. Although Q remained at only 70% of control, renal blood flow and renal function (glomerular filtration rate, urinary sodium excretion, urine output, osmolar clearance, and free water clearance) were restored to control values. Our results suggest that the impairment in renal function during PEEP is not caused by changes in intrarenal blood flow distribution, Q, or hepatic congestion, but rather by a decrease in intravascular volume.

A model for the study of the oral administration of peptide hormones

The intragastric administration of lysine vasopressin (LVP) to rats is used as a model to study the biological activity of orally administered peptide hormones. Using a modification of the antidiuretic assay of Sawyer, LVP given by stomach tube caused a significant antidiuresis that was dose dependent in doses of 300 to 2000 mU. The simultaneous administration of the protease inhibitor, Trasylol, increased the antidiuretic effect of LVP. The synthetic peptide (1-deamino, 4 valine)-8-D-arginine-vasopressin also caused a dose-dependent prolonged and significant antidiuresis. No pressor effect was observed after intragastric administration of LVP in doses up to 40 U/rat. We are now using this model to test other procedures for enhancing the activity of lysine vasopressin administered in the gastrointestinal tract such as encapsulation into liposomes. The information gained with vasopressin will then be applied to insulin with the ultimate goal of making oral administration practical.

Mechanism of effect of hypoxia on renal water excretion.

The effect of lowering the pressure of oxygen from 80 to 34 mm Hg was examined in anesthetized dogs that were undergoing a water diuresis. This degree of hypoxia was associated with an antidiuresis as urine osmolality (Uosm) increased from 107 to 316 mosmol/kg H(2)O (P < 0.001) and plasma arginine vasopressin increased from 0.06 to 7.5 muU/ml, (P < 0.05). However, hypoxia was not associated with significant changes in cardiac output (CO, from 4.2 to 4.7 liters/ min), mean arterial pressure (MAP, from 143 to 149 mm Hg), glomerular filtration rate (GFR, from 46 to 42 ml/min), solute excretion rate (SV, from 302 to 297 mosmol/min), or filtration fraction (from 0.26 to 0.27, NS). Hypoxia was associated with an increase in renal vascular resistance (from 0.49 to 0.58 mm Hg/ml per min, P < 0.01). The magnitude of hypoxia-induced antidiuresis was the same in innervated kidneys and denervated kidneys. To further examine the role of vasopressin in this antidiuresis, hypoxia was induced in hypophysectomized animals. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in hypophysectomized animals was the same as in intact animals. In contrast to intact animals, however, hypoxia did not induce a significant antidiuresis in hypophysectomized animals (Uosm from 72 to 82 mosmol/kg H(2)O). To delineate the afferent pathway for hypoxia-stimulated vasopressin release, hypoxia was induced in dogs with either chemo- or baroreceptor denervation. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in the denervated animals was the same as in nondenervated animals. Hypoxia resulted in an antidiuresis in chemoreceptor (Uosm from 113 to 357 mosmol/kg H(2)O, P < 0.001) but not in baroreceptor (Uosm from 116 to 138 mosmol/kg H(2)O, NS) denervated animals. To determine if hypoxia alters renal response to vasopressin, exogenous vasopressin was administered to normoxic and hypoxic groups of dogs. The antidiuretic effect of vasopressin was no different in these two groups. These results demonstrate that hypoxia induces an antidiuresis which is independent of alterations in CO, MAP, SV, filtration fraction, renal nerves, or renal response to vasopressin and occurs through baroreceptor-mediated vasopressin release. The nature of the baroreceptor stimulation remains to be elucidated.