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Biomedical subjects

M L Kauker

Publications and source records attributed to M L Kauker.

At least 19 recordsLinked to original sources
PubMed1997

Renal response to volume expansion in streptozotocin-induced diabetic rats: influence of calcium channel blockade.

The renal response to volume expansion (VE) has been shown to be impaired in streptozotocin (STZ)-induced diabetes. This may contribute to the abnormal maintenance of fluid balance in diabetics. Since calcium channel blockade (CaCb) has been shown to improve renal hemodynamic and tubular functions, the present studies were designed to examine the ability of CaCb to enhance the response of kidneys from diabetic rats to a volume load. Rats were made diabetic by a single injection of STZ (65 mg i.p.), while the control rats received only a vehicle injection. Nisoldipine, a CaCb agent was given to half of the diabetic rats in a dose of 0.015 microgram/kg per min during the acute experiment. The left kidney was denervated in each rat while the right kidney remained innervated. Glomerular filtration rate (GFR) was elevated during VE in all of the rats except in the denervated kidneys of diabetic rats. Nisoldipine improved GFR in most cases. Urine flow increased markedly during VE. This response was enhanced by denervation but depressed in the diabetic rats. Nisoldipine improved the defective volume reflex in primarily the denervated kidneys. Changes in net urinary excretion of water and sodium during VE were significantly lower in the diabetic rats than in the control group. In the nisoldipine treated diabetic rats the VE induced changes in water and sodium excretion returned toward normal in the denervated, but not in the innervated kidneys. The data are consistent with a blunted volume reflex in the diabetic rats that may be improved by CaCb. Impaired sympatho-inhibition in diabetic rats appears to oppose the effects of VE and nisoldipine treatment. CaCb may contribute to the volume reflex by enhanced filtration as well as by reduced tubular reabsorption.

Animals↗
PubMed1992

Post-obstruction diuresis: influence of renal prostaglandins.

The possible role of altered renal prostaglandin metabolism in the generation of post-obstruction diuresis (POD) was examined in 16 adult male Sprague-Dawley rats. Inhibition of cyclooxygenase by the administration of a combination of two nonsteroidal anti-inflammatory drugs (NSAID), meclofenamate and indomethacin in 8 of these rats exaggerated, rather than lowered the degree of natriuresis and diuresis that followed the release 24 h after bilateral ureteral ligation. Urine osmolarity was similar in the two groups of rats treated with the NSAID and vehicle. The results suggest an enhanced synthesis of renal vasoconstrictor and antidiuretic prostaglandins (thromboxane A2 or PGF2 alpha) during bilateral ureteral ligation. NSAIDs such as aspirin, indomethacin, meclofenamate and others may promote POD by blocking this prostaglandin pathway while promoting the cytochrome P450 monooxygenase pathway which may produce vasodilator, diuretic and natriuretic paracrine hormones. Additionally, inhibition of prostaglandin synthesis may have enhanced post-obstruction diuresis in the present studies by allowing a greater volume expansion during obstruction, as indicated by a reduced hematocrit in the rats that were pretreated with NSAID.

Analysis of Variance↗
PubMed1992

Normalization of pressure-natriuresis by nisoldipine in spontaneously hypertensive rats.

This study examined whether the calcium antagonist nisoldipine can shift the relations between sodium excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure toward lower pressures in spontaneously hypertensive rats. Mean arterial pressure decreased similarly by 9% and 12% in Wistar-Kyoto and spontaneously hypertensive rats after nisoldipine (0.5 microgram/kg bolus + 0.017 microgram/kg/min). Urine flow and sodium excretion increased by 35% and 24% in Wistar-Kyoto rats after nisoldipine. In contrast, urine flow and sodium excretion rose by 121% and 132% in spontaneously hypertensive rats, and fractional sodium excretion rose from 1.9 +/- 0.3 to 4.2 +/- 0.4%. Control sodium excretion, papillary blood flow, and renal interstitial pressure were significantly lower in spontaneously hypertensive rats than in Wistar-Kyoto rats when compared at similar renal perfusion pressures. Sodium excretion, papillary blood flow, and renal interstitial pressure all increased in spontaneously hypertensive rats after nisoldipine, whereas it had no effect on papillary blood flow or renal interstitial pressure in Wistar-Kyoto rats. The relations among sodium excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure were shifted toward lower pressures in spontaneously hypertensive rats given nisoldipine and became similar to those seen in Wistar-Kyoto rats. These results indicate that nisoldipine normalizes the relations among sodium excretion, renal interstitial pressure, papillary blood flow, and renal perfusion pressure in spontaneously hypertensive rats perhaps by correcting the defect in renal medullary perfusion associated with resetting of pressure natriuresis in this model of hypertension.

Animals↗
PubMed1991

Blunting of the renal response to volume expansion by a bradykinin receptor antagonist: influence of denervation.

The interaction of renal sympathetic nervous influences with the intrarenal kallikrein-kinin system was examined during graded expansion of the extracellular fluid volume in rats. One group of rats was pretreated with a specific and highly efficacious competitive antagonist of bradykinin receptor (BKRA), whereas the other group received only a vehicle infusion. The left kidney was denervated in each animal and the right kidney remained intact. After control observations, the extracellular fluid volume was expanded by a continuous i.v. infusion of 0.9% NaCl at a rate of 0.25% of body weight per minute for 40 min (VE). During VE urine flow and sodium excretion increased significantly from both kidneys in each of the two treatment groups. The diuretic response was greatest in the denervated kidneys of vehicle-pretreated rats, where urine flow increased by 70 +/- 13 microliters.min(-1).g kwt(-1). This exaggerated diuresis was blunted by pretreatment with the BKRA. In the denervated and BKRA-treated kidneys, the VE-induced mean urine flow increase was limited to 31 +/- 5 microliters.min(-1).g kwt(-1) (P less than .05 compared with vehicle-pretreated, denervated kidneys). The change in net sodium excretion produced by VE was also reduced by BKRA pretreatment in the denervated kidneys from 13.2 +/- 2.6 to 5.5 +/- 1.3 microEq.min-1.g kwt(-1) (P less than .05, vehicle vs. BKRA). In the intact kidneys the diuretic and natriuretic responses to VE were similar in the vehicle- and BKRA-pretreated rats. Glomerular filtration rate and filtration fraction were increased significantly and to the same extent by VE under all experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Kallidin effect on renal tubular function in meclofenamate- and vehicle-pretreated rats.

The effect of kallidin (lysyl-bradykinin) on the urinary recovery of sodium-22 was examined in anesthetized, volume-expanded rats. Sodium-22 was microinfused into the lumen of late proximal convoluted tubules with and without kallidin (100 pg/ml). Kallidin enhanced mean sodium-22 recovery from a control of 2.24 +/- 0.29% to 6.22 +/- 1.30% (delta = 3.98 +/- 1.31%, P less than 0.005). The urinary recovery of simultaneously microinfused inulin, mean blood pressure, urine flow, and the rate of tubular infusion were similar during control and kallidin microinfusions. Pretreatment of rats with meclofenamate (3.0 mg/kg) to inhibit renal prostaglandin synthesis blunted, but did not abolish, the effect of kallidin to promote sodium-22 recovery. The changes in sodium recovery induced by kallidin represent a 175 +/- 47% and a 58 +/- 11% increase from control values in vehicle- and meclofenamate-pretreated rats, respectively. The results indicate that kallidin, microinfused in high doses into the lumen of late proximal tubules, may lower sodium efflux in that nephron. Inhibition of prostaglandin synthesis reduced the tubular effect of kallidin, suggesting that enhanced prostaglandin synthesis may contribute to the natriuretic effects of kallidin. Alternatively, meclofenamate may directly oppose the tubular effect of kallidin.

Animals↗
PubMed1989

Plasma dilution during transdermal clonidine antihypertensive monotherapy.

In eight hypertensive patients treated with transdermal clonidine for one year, there was plasma dilution, as shown by a reduction in serum sodium, hemoglobin, and serum protein levels. Free water clearance did not change significantly. Plasma dilution was likely sustained by increased water intake due to "dry mouth", as frequently seen with central acting drugs such as clonidine.

Administration, Cutaneous↗
PubMed1987

Augmentation by aprotinin of the renal response to vasopressin.

We contrasted the renal effects of vasopressin in Brattleboro rats with and without pretreatment with aprotinin (20,000 KIU kg-1). In both treatment groups, vasopressin injected at 3 mU kg-1 sec caused in conscious rats elevation of urine osmolality and reduction of urine flow and urinary excretion of total solutes. However, these effects of vasopressin were significantly greater in aprotinin pretreated rats than in rats without aprotinin treatment. In ketamine-pentobarbital-anesthetized rats without aprotinin pretreatment, vasopressin infused at 2 mU kg-1 hr-1 elevated urinary kinin excretion but did not affect urine flow rate or osmolality; in contrast, in aprotinin-pretreated rats, the same dose of vasopressin did not increase urinary kinins but caused elevation of urinary osmolality and reduction of urine flow, solute excretion, and glomerular filtration rate. Aprotinin pretreatment in anesthetized rats also blunted the rise in kinin excretion elicited by vasopressin at a higher dosage, 5 mU kg-1 hr-1, but did not potentiate the vasopressin-induced antidiuresis. We conclude that aprotinin facilitates the expression of the antidiuretic effect of vasopressin at a low, but not at a high dosage. This effect of aprotinin may be a consequence of: renal kallikrein inhibition which prevents augmentation of renal kinins in response to increased vasopressin levels, or other unrecognized properties of aprotinin.

Animals↗
PubMed1987

Renal tubular effect of nisoldipine, a calcium channel blocker, in rats.

The renal tubular effect of nisoldipine (10 micrograms/kg/h) was evaluated using clearance and micropuncture techniques in spontaneously hypertensive rats made diuretic by i.v. infusion of 2.5% NaCl. In one group of 11 rats the renal innervation was intact, whereas in a second group of 10 rats the left kidney was denervated. The drug reduced mean blood pressure in both groups of rats without a significant change in heart rate or glomerular filtration rate. Nisoldipine increased urine flow from 22.3 +/- 2.1 to 26.8 +/- 2.5 microliter/min/100 g BW and from 23.8 +/- 1.3 to 31.5 +/- 1.4 microliter/min/100 g BW in the innervated and denervated rats, respectively (p less than 0.05 for both). Fractional excretion of sodium and total solute were significantly higher under nisoldipine action in both groups of rats, indicating reduced reabsorption of water as well as solute by the nephron. Potassium excretion was unaltered in the innervated rats while in the denervated group it was significantly reduced by the drug. Fractional water excretion was enhanced from 3.3 +/- 0.3% to 4.1 +/- 0.4% of the filtrate in the innervated rats and from 3.4 +/- 0.2% to 4.6 +/- 0.3% in the denervated rats. Tubular fluid to plasma inulin concentration ratios at late distal puncture sites were lowered by nisoldipine in both the innervated kidneys (from 10.5 +/- 1.6 to 8.3 +/- 0.8, with p less than 0.05) and denervated kidneys (from 8.8 +/- 0.5 to 6.7 +/- 0.5, with p less than 0.05). The mean percentage of filtrate reabsorbed between late proximal and late distal tubular fluid collection sites was lowered in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Segmental nephron function in rats treated with aprotinin, an inhibitor of kallikrein.

The effects on kidney function of aprotinin, an inhibitor of kallikrein and other serine proteinases, were investigated in rats made diuretic by infusion of 0.9% saline. Late proximal, early distal and late distal tubular fluid samples were collected before and after aprotinin administration (20,000 kallikrein I.U./kg b.wt. i.v.). Glomerular filtration rate and urinary excretion of solute and water were assessed simultaneously. Aprotinin did not alter blood pressure or glomerular filtration rate, but reduced urine flow from 23.8 +/- 4.5 to 16.4 +/- 3.4 microliter min-1 100 g-1 (P less than .05) and urinary kinin excretion from 23.5 +/- 3.2 to 10.8 +/- 1.9 pg min-1 100 g-1 (P less than .01). Aprotinin increased the tubular fluid to plasma inulin concentration ratio at late distal tubule puncture site, but not at late proximal or early distal tubule collection sites. Estimates of fluid reabsorption in the distal convoluted tubule, expressed as a percentage of glomerular filtration rate, as a percentage of delivery to this nephron segment or as net volume transported, increased after the administration of aprotinin by 22, 24 and 23% (P less than .05), respectively. In contrast, aprotinin did not alter the estimates of fluid reabsorption in the proximal convoluted tubule, the loop of Henle or the collecting tubule. We conclude that the antidiuretic effect of aprotinin in saline-expanded rats is related to selective augmentation of fluid reabsorption in the distal convoluted tubule. This effect of aprotinin may be the expression of reduced renal kinin levels, inhibition of serine proteases other than kallikrein or other unrecognized properties of the agent.

Absorption↗
PubMed1985

Renal effects of aprotinin, a kallikrein inhibitor in rats in saline diuresis.

Administration of aprotinin, a kallikrein inhibitor, to anesthetized rats infused with 0.9% saline solution to expand the extracellular fluid volume resulted in blunted natriuresis and diuresis. Urine flow declined from 27.1 +/- 2.6 to 8.0 +/- 0.9 microliter/min/100 g body wt while sodium and potassium excretion were reduced 63 and 45%, respectively (P less than 0.01). Mean blood pressure and glomerular filtration rate were not significantly altered by aprotinin. Acute or chronic pretreatment with DOCA, to enhance kinin synthesis, failed to modify the renal excretory response to aprotinin suggesting that saline loading alone was able to induce kinin generation fully in these rats. The results indicate that aprotinin enhanced the reabsorption of filtrate in rats expanded with isotonic saline and imply an influence of renal kinins on the tubular transport of salt and water.

Animals↗
PubMed1984

Role of vasopressin in regulation of renal kinin excretion in Long-Evans and diabetes insipidus rats.

To study the relationship between vasopressin and the renal kallikrein-kinin system we measured the rate of excretion of kinins into the urine of anesthetized rats during conditions of increased and decreased vasopressin level. The excretion of immunoreactive kinins in Brattleboro rats with hereditary diabetes insipidus (DI) (24 +/- 3 pg min-1 kg-1) was lower than in the control Long Evans (LE) rats (182 +/- 22 pg min-1 kg-1; P less than 0.05). The DI rats also exhibited negligible urinary excretion of immunoreactive vasopressin, reduced urine osmolality, and increased urine flow and kininogenase excretion. In LE rats, volume expansion by infusion of 0.45% NaCl-2.5% dextrose to lower vasopressin secretion reduced (P less than 0.05) kinin excretion, vasopressin excretion, and urine osmolality to 41, 26, and 15% of their respective control values, while increasing (P less than 0.05) urine flow and kininogenase excretion. On the other hand, the infusion of 5% NaCl, which promotes vasopressin secretion, increased (P less than 0.05) the urinary excretion of kinins and vasopressin to 165 and 396% of control, while increasing (P less than 0.05) urine flow and kininogenase excretion. Infusion of vasopressin (1.2 mU/h, intravenous) enhanced (P less than 0.05) kinin excretion by two to threefold in DI rats and in LE rats during volume expansion with 0.45% NaCl-2.5% dextrose, while decreasing urine flow and increasing urine osmolality. This study demonstrates that the urinary excretion of immunoreactive kinins varies in relation to the urinary level of vasopressin, irrespective of urine volume and osmolality and of the urinary excretions of sodium and kininogenase. The study suggests a role for vasopressin in promoting the activity of the renal kallikrein-kinin system in the rat.

Animals↗
PubMed1981

Digoxin transport in the distal nephron of rats during saline diuresis.

The nephron segments involved in the renal tubular transport of digoxin and the direction of transport in each segment were evaluated using renal micropuncture techniques in 11 rats made diuretic by i.v. infusion of .85% saline. Tubular fluid was collected from 4 different sites along the nephron: late proximal, early distal, late distal, and ureter. The concentrations of 3H-digoxin and 14C-inulin were measured in each sample and the reabsorption of water and efflux of digoxin were calculated. Water was removed from the lumen along the entire length of the nephron and only 2.53 +/- 0.3% of the filtrate was excreted in the urine. Digoxin was also absorbed in the proximal convoluted tubule and in the loop of Henle. About 1/3 of the filtered drug exited in these early nephron segments probably by passive diffusion. In the distal convoluted tubule, digoxin was added to the tubular fluid. The fraction of digoxin present in the lumen increased form 64 +/- 3.8% of the filtered load at early distal site to 78.7% +/- 4.8% at late distal site indicating that an amount equal to 15% of filtered digoxin entered the tubule. This influx occurred against a concentration of 3-5, suggesting the existence of a carrier mediated or active transport mechanism in this nephron segment. Transport of digoxin beyond the late distal puncture site was negligible. The collecting duct appeared to be relatively impermeable to the drug since a concentration gradient of 30 or greater failed to cause its diffusion out of the tubule. The data indicate bidirectional transport of digoxin in the rat nephron. Efflux occurs primarily in the early nephron segments while net influx is limited to the distal convoluted tubule.

Animals↗
PubMed1981

Effect of prostaglandin synthesis inhibitors on clonidine-induced diuresis in rats.

Clonidine is a centrally acting antihypertensive drug that also has marked renal effects. The role of renal prostaglandins in clonidine-induced diuresis was examined in anesthetized and conscious rats. Twelve surgically prepared rats were pretreated with either of two inhibitors of prostaglandin synthesis, indomethacin or meclofenamate (2 mg/kg), while thirteen rats served as controls. Clonidine (200 micrograms/kg/hr, i. v.) increased urine flow tenfold in both pretreated and nonpretreated controls whereas blood pressure and glomerular filtration rate were reduced by clonidine. Fractional excretions of sodium, potassium, total solute and water were enhanced similarly in these two groups of anesthetized rats. Experiments were also conducted in ten conscious rats pretreated with vehicle, indomethacin (2.0 and 7.5 mg/kg), or meclofenamate (2 mg/kg) prior to clonidine infusion. Marked diuresis occurred whether these rats were pretreated with vehicle or one of the nonsteroidal antiinflammatory drugs (NSAID). Thus, NSAID did not prevent the renal excretory response to clonidine in either anesthetized or conscious rats, suggesting that enhanced prostaglandin synthesis is not an essential component of the diuretic action of this drug in rats.

Anesthesia↗