pituitrin and Ureteral-Obstruction

Topics: Acute Kidney Injury; Animals; Disease Models, Animal; Female; Furosemide; In Vitro Techniques; Ischemia; Kidney; Kidney Tubules; Mannitol; Perfusion; Rabbits; Ureteral Obstruction; Vasopressins

The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

Topics: Acute Disease; Analgesics; Humans; Hypercalcemia; Immune System Diseases; Kidney Calculi; Kidney Concentrating Ability; Kidney Diseases; Kidney Tubular Necrosis, Acute; Necrosis; Nephrosis; Nephrotic Syndrome; Potassium Deficiency; Proteins; Tetracyclines; Ureteral Diseases; Ureteral Obstruction; Urologic Neoplasms; Vascular Diseases; Vasopressins

Topics: Aged; Diuresis; Drainage; Humans; Infant; Kidney; Male; Middle Aged; Natriuresis; Polyuria; Postoperative Complications; Prostatic Hyperplasia; Prostatic Neoplasms; Ureteral Calculi; Ureteral Obstruction; Urinary Bladder Neck Obstruction; Urologic Diseases; Vasopressins; Water-Electrolyte Balance

Topics: Adenine Nucleotides; Adenosine Triphosphate; Angiotensins; Blood Circulation; Blood Circulation Time; Blood Pressure; Diuresis; Dye Dilution Technique; Hemodynamics; Kidney; Mannitol; Metabolism; Osmosis; Papaverine; Physiology; Renin; Sodium; Ureteral Obstruction; Vasopressins

Ureteral obstruction is marked by disappearance of the vasopressin-dependent water channel aquaporin-2 (AQP2) in the renal collecting duct and polyuria upon reversal. Most studies of unilateral ureteral obstruction (UUO) models have examined late time points, obscuring the early signals that trigger loss of AQP2.. We performed RNA-Seq on microdissected rat cortical collecting ducts (CCDs) to identify early signaling pathways after establishment of UUO.. Vasopressin V2 receptor (AVPR2) mRNA was decreased 3 hours after UUO, identifying one cause of AQP2 loss. Collecting duct principal cell differentiation markers were lost, including many not regulated by vasopressin. Immediate early genes in CCDs were widely induced 3 hours after UUO, including. Immediately after establishment of UUO, collecting ducts manifest a stunned state with broad disappearance of mRNAs. Within 3 hours, there is upregulation of immediate early and inflammatory genes and disappearance of the V2 vasopressin receptor, resulting in loss of AQP2 (confirmed by lipopolysaccharide administration). The inflammatory response seen rapidly after UUO establishment may be relevant to both UUO-induced polyuria and long-term development of fibrosis in UUO kidneys.

Topics: Animals; Aquaporin 2; Kidney; Kidney Tubules, Collecting; Polyuria; Rats; RNA, Messenger; Ureteral Obstruction; Vasopressins

The expression of aquaporin-2 (AQP2) is decreased in rats with bilateral ureteral obstruction (BUO) and unilateral ureteral obstruction (UUO). Therefore, the expression of additional renal aquaporins (AQP1-4) and phosphorylated AQP2 (p-AQP2), known to play a role in urinary concentration, was examined in a Wistar rat model with 24 h of UUO. In obstructed kidneys, immunoblotting revealed a significant decrease in the expression of inner medullary AQP2 to 42 +/- 4, p-AQP2 to 23 +/- 5, AQP3 to 19 +/- 6, AQP4 to 11 +/- 5, and AQP1 to 64 +/- 8% of sham levels. AQP1 expression located in the proximal tubule decreased to 74 +/- 4% of sham levels (P < 0.05). Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p-AQP2. In contralateral nonobstructed kidneys, immunoblotting also revealed significant reductions of AQP1 in the inner medulla, outer medulla, and cortex, whereas expression of AQP2, AQP3, AQP4, and p-AQP2 was unchanged. Furthermore, we collected the urine from both obstructed and nonobstructed kidneys for 2 h, respectively, after 24 h of UUO. Urine collection from obstructed kidneys during 2 h after release of UUO revealed a significant reduction in urine osmolality and solute-free water reabsorption (T(c)H(2)O). Moreover, an increase in urine production and T(c)H(2)O was observed in contralateral kidneys. To examine whether vasopressin-independent mechanisms are involved in AQP2 regulation, vasopressin-deficient Brattleboro (BB) rats with 24 h of UUO were examined. Immunoblotting revealed downregulation of AQP2, p-AQP2, AQP3, and AQP1 in obstructed kidneys and downregulation of p-AQP2 and AQP1 in nonobstructed kidneys. In conclusion, 1) UUO is associated with severe downregulation of AQP2, AQP3, AQP4, and AQP1; thus all of these AQPs may play important roles in the impaired urinary concentrating capacity in the obstructed kidney; 2) the reduced levels of AQP1 in the nonobstructed kidney may contribute to the compensatory increase in urine production; and 3) downregulation of AQPs in BB rats supports the view that vasopressin-independent pathways may be involved in AQP2 and AQP3 regulation in the obstructed kidney.

Topics: Animals; Aquaporin 1; Aquaporin 2; Aquaporin 3; Aquaporin 4; Aquaporin 6; Aquaporins; Down-Regulation; Kidney; Kidney Concentrating Ability; Male; Rats; Rats, Wistar; Reference Values; Ureteral Obstruction; Vasopressins

Acute unilateral obstruction (UUO) of the pig kidney is associated with an increased secretion of intrarenally generated angiotensin II (ANG II). In order to clarify the importance of this intrarenal ANG II generation during acute UUO, ipsilateral and contralateral renal blood flow and renal secretion rate of ANG II were determined in pigs during continuous infusion of an angiotensin I converting enzyme (ACE) inhibitor. Pigs were operatively equipped with electromagnetic flow probes and catheters in the renal veins and aorta. Intravenous administration of the ACE inhibitor SQ14225 (captopril), 1 mg/kg per hour, resulted in a significant increase in renal blood flow in the contralateral kidney from 340 +/- 28 ml/min to 435 +/- 36 ml/min (P < 0.01), whereas renal blood flow in the ipsilateral kidney was significantly reduced from 388 +/- 23 ml/min to 248 +/- 24 ml/min, similar to the reduction in controls. Captopril reduced mean aortic blood pressure, renal vascular resistance consistently on both sides, and plasma concentrations of ANG II and aldosterone from all sample sites. Renal secretion rate of ANG II showed a clear tendency to be reduced from the ipsilateral kidney. The results suggest that in UUO a compensatory increase in renal blood flow may be inhibited in part due to an enhanced secretion of ANG II in the ipsilateral kidney. However, a captopril-mediated inhibition of bradykinin breakdown may also explain some of the observed changes.

Topics: Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Female; Hemodynamics; Kidney; Pelvis; Pressure; Renal Circulation; Swine; Ureteral Obstruction; Vascular Resistance; Vasopressins

Polyuria after release of bilateral ureteral obstruction (BUO) is frequently seen in patients with urological disorders. In this study, we examined the effect of BUO and release of BUO on the expression of the vasopressin-regulated water channel aquaporin-2 (AQP-2) in rat kidney. Ureters were obstructed for 24 h in all experiments, and BUO was either not released or released for 24 or 48 h or 7 days. Each group of experimental rats were matched with sham-operated controls. One kidney was used for membrane fractionation and immunoblotting, whereas the contralateral was fixed for immunocytochemistry. Immunoblotting demonstrated a significant reduction in AQP-2 expression in inner medullar during 24 h of BUO to 26 +/- 8% (P < 0.001). Release of BUO was associated with immediate onset of a predominant osmotic-dependent polyuria. Forty-eight hours after release of BUO, the reduction in AQP-2 expression persisted (19 +/- 8%, P < 0.001), concurrent with a marked nonosmotic postobstructive polyuria, as determined by a significant reduction in free-water clearance (-50 +/- 7 vs. -85 +/- 10 microliters.min-1.kg-1, P < 0.05). Immunofluorescence and immunoelectron microscopy confirmed the reduced levels of AQP-2 in collecting duct principal cells. Seven days after release, the renal excretion of water and electrolytes had almost normalized. However, the downregulation of AQP-2 was not partly reversed (49 +/- 14%, P < 0.001), and, consistent with this, the urinary concentrating capacity was significantly reduced 7 days after release to a 18-h period of thirst. This strongly suggests that the persistent downregulation of AQP-2 is the cause of the slow recovery in concentration capacity. In conclusion, BUO and release of BUO were associated with a marked reduction in expression of AQP-2, coincident with the development and maintenance of postobstructive polyuria. Thus reduced AQP-2 levels may represent an important factor in the slow recovery from postobstructive diuresis.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Fluorescent Antibody Technique; Immunoenzyme Techniques; Ion Channels; Kidney; Male; Microscopy, Immunoelectron; Polyuria; Rats; Rats, Wistar; Tissue Distribution; Ureteral Obstruction; Vasopressins

Bleeding time is prolonged following resection of kidney tissue as well as after ureteral occlusion. Bilateral nephrectomy raises bleeding time from 17 to 67 min, and blood loss can be increased from 2 to 12 microliters/min. Plasmatic coagulation factors remain unchanged in uremic rats. There is no influence of various surgical interventions producing uremia on function of thrombocytes. In rats with intact kidney function and following bilateral nephrectomy a diminution of bleeding time is demonstrable after administration of histamine or captopril. Shortening of bleeding time by the antifibrinolytic substance p-aminomethylbenzoic acid seems to indicate an increased fibrinolytic activity in uremic rats.

Topics: 4-Aminobenzoic Acid; Angiotensin II; Animals; Bleeding Time; Blood Coagulation; Captopril; Chlorisondamine; Enalapril; Female; Fibronectins; Histamine; Nephrectomy; para-Aminobenzoates; Platelet Aggregation; Rats; Rats, Inbred Strains; Uremia; Ureteral Obstruction; Vasopressins

After unilateral release of bilateral ureteral obstruction (BUO), there is a significant increase in renal vasoconstriction that accounts for the marked decrease in glomerular filtration rate and effective renal plasma flow seen in this setting. We examined the potential role of antidiuretic hormone (ADH), a vasoconstrictor of the renal circulation, on renal hemodynamics in female Sprague-Dawley rats with BUO of 24-hr duration. Rats with BUO had significantly higher plasma values of ADH 65.1 +/- 12.2 vs. 12.1 +/- 4.1 pg/ml), sodium (145.4 +/- 0.91 vs 138.6 +/- 1.06 mEq/liter), and osmolality (375.6 +/- 2.0 vs 310.1 +/- 3.6 mOsm/kg) than sham-operated rats. Rats with BUO pretreated with enalapril, an angiotensin-converting enzyme inhibitor, before obstruction had somewhat higher, but not significantly different, plasma values for ADH (84.6 +/- 20.8 pg/ml) than rats with BUO not given enalapril. Rats with unilateral ureteral obstruction of 24-hr duration had plasma levels of ADH (8.2 +/- 1.3) not different from those in sham-operated rats. Rats with BUO pretreated with a specific antagonist of the V1-type receptor for ADH had significantly greater values for the glomerular filtration rate (2.31 +/- 0.24 vs 1.44 +/- 0.08 ml/min/kg body wt) and the effective renal plasma flow (8.95 +/- 0.71 vs 3.81 +/- 0.44 ml/min/kg body wt) and significantly lower values for mean arterial pressure (140.3 +/- 2.0 vs 159.1 +/- 5.5 mm Hg) than did BUO rats not given the antagonist. The results indicate that high levels of ADH play an important role in the decrease in the glomerular filtration rate and effective renal plasma flow observed in rats with BUO of 24 hr. The significant increase in ADH levels after BUO of 24-hr duration may be due to an increase in osmotic stimulation as a consequence of hypernatremia. Activation of the renin-angiotensin axis, known to occur after BUO or unilateral ureteral obstruction of 24-hr duration, does not appear to have a role in the increased circulating levels of ADH.

Topics: Animals; Blood Pressure; Enalapril; Female; Glomerular Filtration Rate; Hematocrit; Kidney Function Tests; Potassium; Rats; Rats, Inbred Strains; Reference Values; Sodium; Ureteral Obstruction; Urine; Vasopressins

Ureteral obstruction affects the kidney's ability to conserve water and sodium. Using the isolated perfused tubule technique, we studied cortical collecting tubules (CCT) taken from rabbits subjected to a sham operation or to 4 h of unilateral ureteral obstruction (UUO). Tubules were perfused in the presence of an osmotic gradient directed to promote water movement from lumen to bath, and volume flux (Jv), hydraulic water permeability (Lp), and transepithelial voltage (V1) were determined. In tubules from sham-operated and UUO animals, basal (before exposure to vasopressin) J, and Lp were not different from zero. After addition of 200 microU . ml-1 of arginine vasopressin (aVP) to the bath, Jv and Lp increased to 1.64 +/- 0.23 nl . mm-1 . min-1 and 127.9 +/- 19.8 cm . s-1 . atm-1 x 10(7), respectively, in tubules from sham-operated animals, but not only 0.27 +/- 0.09 nl . mm-1 . min-1 an 18.8 +/- 6.2 cm . s-1 . atm-1 . 10(7) in tubules from UUO animals. Pretreatment with desoxycorticosterone acetate (DOCA) or indomethacin in vivo did not prevent the blunted vasopressin response seen in tubules taken from UUO animals. The Jv and Lp responses to the cyclic AMP (cAMP) analogue, 8-Br-cAMP, were also diminished in tubules taken from UUO animals compared with shams. V1, measured during the basal period, was diminished in tubules from UUO kidneys (-5.0 +/- 2.1 mV) compared with shams (-21.9 +/- 4.1 mV), and pretreatment with DOCA did no prevent the effects of UUO on V1. In contrast, tubules taken from animals that received indomethacin prior to UUO developed voltages not different from voltages in tubules taken from sham-operated animals (-17.3 +/- 1.7 mV). We conclude that, although CCT from UUO animals can maintain osmotic gradients, their ability to respond to vasopressin by increasing Lp is impaired by an intrinsic defect located at a step beyond the generation of cAMP, and that prostaglandin inhibition or DOCA pretreatment do not reverse the decreased responsiveness of Lp to aVP. UUO also diminished V1, and this abnormality was prevented by previous treatment with indomethacin, suggesting that prostaglandins may mediate the effect of UUO on V1.

Topics: Adrenal Cortex Hormones; Animals; Bucladesine; Electric Conductivity; Female; Kidney Tubules; Kidney Tubules, Collecting; Osmotic Pressure; Prostaglandins; Rabbits; Ureteral Obstruction; Vasopressins; Water-Electrolyte Balance

Micropuncture and microcatheterization studies have been used extensively to investigate the pathophysiologic alterations in renal function induced by urinary tract obstruction. The present isolated tubule microperfusion studies were designed to examine the intrinsic alterations in segmental nephron function induced by 24 h of bilateral (BUO) and unilateral (UUO) urinary tract obstruction. Following UUO superficial proximal convoluted tubule reabsorption rate (J(v)) was not different from contralateral control (0.75+/-0.08 vs. 0.73+/-0.11 nl/mm per min, NS). Following UUO J(v) in juxtamedullary proximal convoluted tubules (JMPCT) was reduced 32% (0.69+/-0.06 vs. 0.47+/-0.04 nl/mm per min, P < 0.02). Following UUO J(v) in proximal straight tubules (PST) was reduced 52% (0.25+/-0.02 vs. 0.12+/-0.03, P < 0.01). Thick ascending limb (T-ALH) function was assessed by measurement of ability to lower perfusate chloride ion concentration (DeltaCl). Following UUO DeltaCl was reduced 76% (-39+/-9 vs. -9+/-1 meq/liter, P < 0.001). Cortical collecting tubule (CCT) function was assessed by measurement of antiduiretic hormone (ADH)-dependent osmotic water flow. Following UUO osmotic water flow was reduced 76% (0.90+/-0.08 vs. 0.22+/-0.04 nl/mm per min, P < 0.01) and this ADH resistance could not be overcome by cAMP. Nephron segments were then examined following relief of BUO. There were no differences in intrinsic function following relief of BUO when compared with UUO. We conclude that in UUO and BUO (a) the intrinsic tubular defects are identical, (b) the natriuresis noted is due, in part, to disordered JMPCT, PST, and T-ALH NaCl reabsorption, (c) the impaired concentrating ability is due, in part, to depressed function in T-ALH and ADH resistance of the CCT, and (d) the ADH resistance occurs at a site distal to the intracellular generation of cAMP.

Topics: Animals; Cyclic AMP; Disease Models, Animal; Diuresis; Functional Laterality; Kidney; Kidney Concentrating Ability; Kidney Tubules; Kidney Tubules, Collecting; Natriuresis; Rabbits; Ureteral Obstruction; Vasopressins

Differential renal function studies performed on ten patients after release of unilateral hydronephrosis revealed that the previously obstructed kidney exhibits abnormalities in a number of physiological indexes. Many of the obstructed kidneys had an impairment of glomerular filtration rate, concentrating ability, acidification, sodium reabsorption and tubular maximal secretion of para-aminohippurate with normal urinary dilution. Despite impairment of sodium and water reabsorption, none of these patients, nor 20 additional patients, had a significant postobstructive diuresis from the previously obstructed kidney. All of the patients had normal total renal function. Thus, the changes observed were a result of the obstructive injury and were not related to azotemia or aberrations in water or sodium metabolism.

Topics: Adolescent; Adult; Aminohippuric Acids; Child; Chronic Disease; Desoxycorticosterone; Diuresis; Glomerular Filtration Rate; Humans; Hydronephrosis; Inulin; Kidney; Kidney Concentrating Ability; Mannitol; Ureteral Obstruction; Vasopressins

Topics: Adolescent; Diabetes Insipidus; Diuretics; Female; Humans; Hydrochlorothiazide; Hydronephrosis; Hypertrophy; Infant; Kidney Diseases; Male; Postoperative Complications; Sodium; Ureteral Obstruction; Ureterocele; Urinary Bladder Diseases; Urography; Vasopressins; Water

Topics: Angiotensin II; Animals; Blood Pressure; Female; Hypertension, Renal; Hypoxia; Kidney; Nephrectomy; Norepinephrine; Rats; Renin; Ureteral Obstruction; Vasopressins

Topics: Aged; Aldosterone; Ammonium Chloride; Blood Urea Nitrogen; Diuresis; Humans; Male; Prostatic Neoplasms; Ureteral Obstruction; Vasopressins

Topics: Aminohippuric Acids; Animals; Blood; Calcium; Chlorides; Diabetes Insipidus; Diuresis; Kidney Function Tests; Kidney Tubules; Mannitol; Potassium; Rats; Sodium; Ureteral Obstruction; Urine; Vasopressins; Water-Electrolyte Balance