Linaria ramosissima (Wall.) Janch., Scrophulariaceae, a folklore plant, has been claimed for its diuretic activities by traditional practitioners. The present study was undertaken to investigate the diuretic activity of L. ramosissima leaves in albino rats. Suspension of leaf powder in 2% gum acacia was administered to experimental rats orally at doses of 450 mg/kg. The diuretic effect was evaluated by measuring the urine volume, pH of urine, and urinary electrolyte excretion. Administration of the test drug increased the urine volume in a non-significant manner, while it enhanced the urinary excretion of sodium, chloride, and potassium significantly, in comparison to the control group. From the present study it can be concluded that the leaves of L. ramosissima have a significant diuretic activity.
Diuretic activity; electrolyte excretion; folklore plant; Linaria ramosissima
The purpose of the present study was to evaluate the diuretic activity of Veerataru [Dichrostachys cinerea (Linn.)] Kwatha in experimental animals by following the standard procedure. Randomly selected animals were divided into three groups of six animals each. The root of Veerataru was administered orally in the form of Kwatha at a dose of 5.4 and 10.8 ml/kg. Parameters like volume of urine, pH of urine and urinary electrolyte concentrations like sodium, potassium and chloride were studied. Veerataru Kwatha increased the urine output in a dose-dependent manner. However, it did not affect the urinary electrolyte concentrations. From the present study, it can be concluded that the root of Veerataru has diuretic property.
Dichrostachys cinerea; diuretic activity; Veerataru Kwatha
The benzene, alcoholic and aqueous root extracts (75mg/kg each)of Dalbergia spinosa Roxb were studied for its diuretic activity by using male albino rats by adopting the method of Tipschitz. The alcoholic extract increased the urine volume and electrolytes sodium, potassium and chloride, which is similar to the standard drug Furosemide (100mg/ kg) by inhibiting sodium, potassium, and chloride ion co-transport at thick ascending loop of henle. The present study showed that the alcoholic extract has significant diuretic activity comparable with standard drug Furosemide in producing urinary output and excretion of sodium,potassium and chloride in mEq/ lit/ 6 hrs
Diuretic; Dalbergia spinosa Roxb. Male albino rats; Furosemide
The hydroalcoholic extracts prepared from leaves of Rungia pectinata and Rungia repens were investigated for antiinflammatory and diuretic activity in wistar rats. The results obtained were compared with that of standard drug aspirin and frusemide for their antiinflammatory and diuretic activity respectively. The acute toxicity study was also carried out using adult swiss albino mice of either sex which indicates the safety of the extracts even at a dose of 4000 mg/kg. R. pectinata showed better anti-inflammatory activity than R. repens. In the present study, it was demonstrated that hydroalcoholic extracts of both R. repens and R. pectinata produce diuretic effect by increasing the excretion of Na+, K+ and Cl−. Results showed that R. repens is most effective in increasing urinary electrolyte concentration of Na+ and K+ ions. The antimicrobial potency of the aerial parts of Rungia pectinata and Rungia repens have been studied using the petroleum ether, benzene, chloroform, acetone and ethanol extract against a wide number of bacteria and fungi by disc diffusion method. The ethanol extract at a concentration of 30 to 60 μg/disc showed significant activity against the bacteria and fungus investigated. All the extracts of R. pectinata and R. repens have got moderate action but chloroform and acetone extracts of R. repens and ethanol extract of R. pectinata have got significant activity against Trichophyton mentagrophytes.
Antiinflammatory; diuretic; antimicrobial; Rungia pectinata and Rungia repens
The aqueous and ethanolic extract of leaves of Coleus aromaticus was evaluated for diuretic activity. Both extracts were evaluated by determination of urine volume and electrolyte concentration in albino rats. Results revealed that both the aqueous and ethanolic extract at dose 500mgl kg showed significant diuretic activity by increasing the total volume of urine and concentration electrolyte. Furosamide (10 mg/kg) was used as reference drug while normal saline (0.9%) solution was used as control.
Diuretic activity; Coleus aromaticus; Furosamide
To study the diuretic effects of cleistanthin A and cleistanthin B, phytoconstituents were isolated from the leaves of Cleistanthus collinus in Wistar rats. The in vivo diuretic effects of cleistanthins A and B were determined according to the Lipschitz test. Prior to the experiment, the animals were fasted for 5 h and placed individually in metabolic cages. Cleistanthins A and B (12.5, 25, and 50 mg/kg) and furosemide (5 mg/kg) were suspended in 0.5% w/v carboxymethyl cellulose and administered orally. The urine was collected up to 5 h after administration and subsequently up to 24 h after administration. The acidity and urine volume were measured immediately. The urinary sodium and potassium levels were determined using a flame photometer, and the chloride level was determined by argentometric titration. The diuretic index and diuretic activity were calculated mathematically. While cleistanthins A and B showed a diuretic index of more than one, the diuretic activity of these compounds was less than one, indicating inferior activity compared with furosemide. Both cleistanthin A and B produced a significant increase in the urine volume and alterations in urinary electrolyte levels. However, the effect of the compounds was not dose dependent. Cleistanthin A and cleistanthin B exert diuretic effects in male Wistar rats without affecting the urinary acidity.
Cleistanthin A; cleistanthin B; diuretic activity
The present study was undertaken to establish the diuretic activity of ethanol and aqueous extract of dried leaves of Garcinia cambogia in rats. Aqueous and ethanol extracts of leaves were administered to experimental rats orally at doses of 100 and 200 mg/kg and compared with furosemide (20 mg/kg, intraperitoneally) as the standard. The parameters measured for diuretic activity were total urine volume, urine concentration electrolytes such as sodium, potassium and chloride have been evaluated . The rats treated with ethanol extract of Garcinia cambogia and aqueous extract of Garcinia cambogia in a dose of 100 and 200 mg/kg showed higher urine output when compared to the respective control. Both ethanol and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group.
Aqueous extract; diuretic activity; ethanol extract; Garcinia cambogia
Water extract of the leaves of Coleus Aromaticus Benth was tested for its diuretic activity in male albino rats. The study was carried out on normal rats using furosemide as a standard reference drug. Rats were treated with furosemide (4 mg/kg. p.o) and Coleus aromaticus (0.5 g/kg and 1.0 g/kg, p/o). Urine was collected and its volume was recorded. Urinary levels of sodium, potassium and chloride were estimated. Treatment with Coleus aromaticus produced diuresis. The urine output and electrolytes concentration was significantly increased. Hence, it is suggested, Coleus aromaticus leaves has diuretic activity on rats.
The whole plant, Pergularia daemia (Family: Asclepediaceae), was extracted with 50% alcohol and a fresh batch of the plant material was successively extracted with petroleum ether, ethyl acetate and n-butanol to determine its diuretic activity. The diuretic activity of the different extracts at a dose of 400 mg/Kg was assessed orally in rats with furosemide as a standard drug using Lipschitzs test. All extracts except the petroleum ether extract showed significant increase (p < 0.001) in urine output. Urinary electrolyte excretion was also affected by the extracts: the alcoholic, ethyl acetate and n-butanol extract caused an increase in the urinary excretion of sodium and potassium ions. These findings suggest that among the mentioned extracts, ethanolic has the maximum diuretic activity followed by n-butanol extract.
Daemia extensa; Diuretic activity; Diuretic action; Electrolyte
Present study was undertaken to evaluate analgesic activity of root of Nelsonia canescens (Lam.) Spreng, a folklore medicinal plant used as the one of the source plant of Rasna. Study was carried out at two dose levels (270 mg/kg and 540 mg/kg) in albino rats. Analgesic activity was evaluated in formalin induced paw licking, and tail flick methods whereas indomethacin and pentazocine were used as standard analgesic drugs, respectively. At both the dose levels, test drug non-significantly decreased paw licking response at both time intervals. In tail flick model, the administration of the test drug increased pain threshold response in a dose dependent manner. In therapeutically equivalent dose level, analgesic activity was observed only after 180 min while in TED ×2 treated group analgesia was observed at 30 min and lasted even up to 240 min. The results suggested that N.canescens root possess moderate analgesic activity.
Analgesic; folklore; gandhamardana hills; Nelsonia canescens; Rasna
The shade-dried powder of leaves of Plectranthus amboinicus (Lour) Spreng was subjected to successive extraction using the various solvents (petroleum ether, chloroform, ethanol and water) in increasing order of polarity. The preliminary phytochemical analyses were carried out for all the extracts. The analyses of the leaves revealed the presence of alkaloids, carbohydrates, glycosides, proteins, amino acids, flavonoids, quinine, tannins, phenolic compounds and terpenoids. Since the phytoconstituents present in the ethanolic and aqueous extracts were similar, both the extracts were selected for further study. The diuretic properties of ethanolic and aqueous extracts were evaluated by determination of urine volume and electrolyte concentration in male albino rats. Furosemide (10 mg/kg) was used as standard while normal saline (0.9%) was used as control. Both ethanolic and aqueous extracts (500 mg/kg) have shown significant increase in the volume of urine and urinary concentration of Na, K and Cl ions. Thus, from the is study it may be concluded that the leaves of P. amboinicus (Lour) Spreng possess diuretic activities.
Diuretic; electrolyte concentration; Plectranthus amboinicus
Nyctanthes arbortristis Linn. is a well documented plant. The present study is done to establish the diuretic activity of the water-soluble portions of the ethanolic extracts of its flowers, barks, seeds and leaves. In toxicity study, the extracts were seen to be safe up to the dose of 2.0 gm/kg. For the estimation of diuretic activity, the parameters studied were total urine volume and urine concentration of Na+, K+ and Cl-. The ethanolic extracts of different plant parts of Nyctanthes arbortristis L. possess significant diuretic activity as reflected by rise in urine volume with cation excretion. The ethanolic extracts of the seeds and leaves at their higher doses exhibited higher electrolyte excretion.
Nyctanthes arbortristis L.; diuretic activity
Twenty patients with cirrhosis and ascites but no renal failure were given piretanide, a new loop diuretic, in order to investigate its efficacy and to relate the diuretic response with the pretreatment plasma aldosterone concentration. Eleven patients responded to piretanide 12 mg/day (equivalent in potency to 80 mg furosemide); there was no response in nine patients. Both groups were similar with regard to liver function, plasma urea, serum creatinine, plasma electrolytes, urine volume, and urine potassium concentration. The basal urinary sodium excretion was significantly higher in those patients who responded (23.6 +/- 5.7 mmol/day vs. 4.3 +/- 1.42 mmol/day; P < 0.01) (M +/- SE). Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were normal or only slightly increased in patients who responded to piretanide (PRA = 1.22 +/- 0.20 ng/ml/h; PAC = 12.25 +/- 2.20 ng/100 ml) and very high in patients who did not respond (PRA = 8.71 +/- 1.18 ng/ml/h; PAC = 84.6 +/- 16.2 ng/100 ml) (P < 0.001). Patients unresponsive to piretanide 12 mg/day also failed to respond when the dose was increased to 24 mg/day. However, the addition of spironolactone, 150 mg/day, to piretanide was followed in these patients by a marked increase in diuresis and natriuresis. These results strongly suggest that the pre-treatment level of aldosterone is an important factor influencing the response to loop diuretics in patients with non-azotaemic cirrhosis and ascites.
The diuretic effect of valproates and its relation to urinary potassium (K+) and chloride (Cl-) excretion have not yet been investigated, so the aim of this study was to evaluate the influence of a single dose of sodium valproate (NaVPA) on 24-h urinary K+ and Cl- excretion in young adult Wistar rats of both genders. For measurement of K+ in urine, the same animals and samples as in our earlier publication were used (Pharmacology 2005 Nov, 75:111–115). The authors propose a new approach to the pathophysiological mechanisms of NaVPA effect on K+ and Cl- metabolism.
Twenty six Wistar rats were examined after a single intragastric administration of 300 mg/kg NaVPA (13 NaVPA-male and 13 NaVPA-female), 28 control intact Wistar rats (14 males and 14 females) were studied as a control group. The 24-h urinary K+, Cl-, creatinine and pH levels were measured.
Total 24-h diuresis and 24-h diuresis per 100 g of body weight were found to be significantly higher in NaVPA-rats of both genders than in rats of the control group (p < 0.05). The data showed NaVPA to enhance 24-h K+ excretion in NaVPA-males and NaVPA-females with significant gender-related differences: 24-h K+ excretion in NaVPA-male rats was significantly higher than in control males (p = 0.003) and NaVPA-female rats (p < 0.001). Regarding the 24-h K+ excretion, NaVPA-female rats did not show a statistically significant difference versus females of the control group (p > 0.05). 24-h urinary K+ excretion per 100 g of body weight in NaVPA-male rats was significantly higher than in control males (p = 0.025). NaVPA enhanced Cl- urinary excretion: 24-h Cl- urinary excretion, 24-h urinary Cl- excretion per 100 g of body weight and the Cl-/creatinine ratio were significantly higher in NaVPA-male and NaVPA-female rats than in gender-matched controls (p < 0.05). 24-h chloriduretic response to NaVPA in male rats was significantly higher than in female rats (p < 0.05).
NaVPA causes kaliuretic and chloriduretic effects with gender-related differences in rats. Further investigations are necessary to elucidate the mechanism of such pharmacological effects of NaVPA.
The diuretic response of normal infants, 6 to 47 days of age, to single doses of mercaptomerin, chlorothiazide, acetazolamide, triamterene and spironolactone was studied by following urinary electrolytes, pH and osmolality. Peak diuresis occured two to four hours after drug administration, and because of compensatory mechanisms little change in urinary excretion was found if only 24-hour urines were studied. Mercaptomerin increased sodium excretion seven-fold, compared to three- to four-fold increases for the other diuretics. Control urinary Na:K ratios averaged 0.68 in infants compared to 2.8 for adults, and mercaptomerin produced the largest increase in this ratio. Qualitatively the response to diuretics is the same in newborn in the ages studied as it is reported to be for adults; no immaturity of the infant kidney in this regard was demonstrated.
Hyperlipidemia/hypercholesteremia are major risk factors for atherosclerosis and cardiovascular diseases. Root of Asparagus racemosus (AR) is widely used in Ayurvedic system of medicine in India and is known for its steroidal saponin content. This study was designed to investigate the hypocholesteremic and antioxidant potential of AR root in both normo- and hypercholesteremic animals. Normal and hypercholesteremic male albino rats were administered with root powder of AR (5 and 10 g% dose levels) along with normal and hypercholesteremic diets, respectively, for a duration of 4 weeks. Plasma and hepatic lipid profiles, fecal sterol, bile acid excretion and hepatic antioxidant activity were assessed. Inclusion of AR root powder in diet, resulted in a dose-dependant reduction in plasma and hepatic lipid profiles, increased fecal excretion of cholesterol, neutral sterol and bile acid along with increases in hepatic HMG-CoA reductase activity and bile acid content in hypercholesteremic rats. Further, AR root also improved the hepatic antioxidant status (catalase, SOD and ascorbic acid levels). No significant changes in lipid and antioxidant profiles occurred in the normocholesteremic rats administered with AR root powder. AR root appeared to be useful as a dietary supplement that offers a protection against hyperlipidemia/hypercholesteremia in hypercholesteremic animals. The results of the present study indicate that the potent therapeutic phyto-components present in AR root i.e. phytosterols, saponins, polyphenols, flavonoids and ascorbic acid, could be responsible for increased bile acid production, elimination of excess cholesterol and elevation of hepatic antioxidant status in hypercholesteremic conditions.
antioxidant; Asparagus racemosus; cholesterol metabolism; hypercholesteremia
Fifty years since their introduction, thiazide diuretics are established as first-line therapy in the treatment of hypertension. Because the dosing profile for thiazide agents lessened, the mechanism responsible for the blood pressure lowering effect may lie outside their diuretic properties. We evaluated the mechanism driving blood pressure reductions in spontaneously hypertensive rats (SHR) and normotensive WKY by examining the effects of low-dose hydrochlorothiazide (HCTZ) administration on renin-angiotensin system (RAS) components. The 7-day, 1.5 mg/kg/day HCTZ did not change systolic pressure in WKY, but decreased SBP by 41 ± 2 mm Hg (p < 0.0001) in SHR. This reduction was independent of increases in water intake, urine output, or alterations in electrolyte excretion. HCTZ significantly increased the plasma concentrations of angiotensin I (Ang I) and angiotensin II (Ang II) in both WKY and SHR while reducing angiotensin converting enzyme (ACE) activity and the Ang II/Ang I ratio (17.1 ± 2.9 before versus 10.3 ± 2.9 after, p < 0.05) only in SHR. HCTZ increased cardiac ACE2 mRNA and activity, and neprilysin mRNA in WKY, but not SHR. Conversely in SHR, ACE2 activity was decreased and aside from a 75% increase in AT1 mRNA in the HCTZ-treated SHR, the expression of the other variables remained unaltered. Measures of cardiac mas receptor mRNA showed no changes in response to treatment in both strains, although cardiac mas mRNA was significantly lower in untreated SHR. These data, which document for the first time the effect of low-dose thiazide on the activity of the ACE2/Ang-(1–7)/mas-receptor axis, suggest that the opposing arm of the system does not substantially contribute to the antihypertensive effect of low-dose thiazides in SHR.
hydrochlorothiazide; angiotensin II; AT1 receptor; angiotensin converting enzyme 2; angiotensin-(1-7); hypertension
The diuretic activity of concentrated ethanolic extract of Aerva lanata (Linn) & Aerva tomentosa Forsk on healthy albino rats were studied with frusemide as reference drug. The urine output increased with concentrated ethanolic extract of Aerva lanata only. In this case the level of electrolytes in urine also increased. But the diuretic activity was mild as compared to frusemide.
Refractory congestive heart failure (CHF) with diuretic resistance is life-threatening and predicts a short life expectancy. Glucocorticoids have been proven to have potent diuretic effects in animal studies; however, their efficacy in CHF patients with diuretic resistance is not known.
Thirteen CHF patients with significant volume overload and diuretic resistance who failed to respond to a conventional sequential nephron blockade therapeutic strategy; that is, the coad-ministration of a thiazide (hydrochlorothiazide) and spironolactone, in combination with loop diuretics, were studied. Prednisone (1 mg/kg daily) was then added to standard care, with other medications unchanged, to determine diuretic efficacy in these CHF patients. Variables included body weight, urine volume, serum electrolytes and renal function.
Adding prednisone resulted in striking diuresis with a mean (± SD) body weight reduction of 9.39±3.09 kg. Prednisone significantly decreased serum creatinine by 52.21±48.68 μmol/L and increased glomerular filtration rate by 33.63±15.87 mL/min/1.73 m2 compared with baseline. All patients were discharged from hospital with improved clinical status and renal function, and 11 patients remained alive in the long term. The main side effect of prednisone appeared to be hyperglycemia in diabetic patients.
The present study demonstrated that prednisone can rapidly eliminate volume overload and improve clinical status and renal function in CHF patients with diuretic resistance. Further prospective randomized clinical studies are warranted to confirm its clinical efficacy.
Diuretic resistance; Furosemide; Heart failure; Prednisone; Renal function; Spironolactone
An antigenic glycosylated cysteine protease has been purified from the latex of Euphorbia nivulia Buch.-Ham. It exhibits remarkable protease activity in the presence of metal ions, oxidizing agents, organic solvents, and detergents. This enzyme showed potential role in leather processing industry due to its dehairing activity for animal hide without hydrolyzing fibrous proteins, producing, by this way, a better quality product. The enzyme can also be used for silver recovering from X-ray plates. In addition, the stability (temperature and surfactants) and hydrolysis of blood stain data also revealed its application in detergent industries. Agriculturally, this protease finds application in biocontrol process against the infectious management of root knot nematode, Meloidogyne incognita. Biologically, it shows noticeable wound healing, haemostatic and antibacterial activity.
Leaves of Echinodorus macrophyllus (EM), from the Alismataceae family, have been used in Brazilian folk medicine for their anti-inflammatory and diuretic properties. In this work, the diuretic and nephroprotective activities of crude extracts of EM were evaluated.
Normal Wistar rats were given 0.9% NaCl containing either EM (10–300 mg/kg), furosemide (13 mg/kg) or arginine vasopressin (0.2 mg/kg). Thereafter, the rats were individually housed in metabolic cages, and urine volume was measured every 30 min for a total of 3 h. Acute kidney injury was induced by gentamicin (GM, 80 mg·kg−1·day−1, b.i.d., 5 days). Along with GM, 0.9% NaCl (control) or EM (30 mg/kg) was given to the rats by gavage.
EM produced a dose-dependent reduction in urine elimination. EM was effective in reversing all GM-induced alterations such as polyuria and glomerular filtration rate reduction. The GM-induced morphological alterations were not observed when EM was given concomitantly with GM.
This study provides evidence that EM possesses nephroprotective effect which indicates that EM may have therapeutic applications in GM-induced acute kidney injury.
Echinodorus macrophyllus Micheli; Alismataceae; Antidiuresis; Gentamicin; Nephrotoxicity
Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (−36.5%, p<0.05), especially in those receiving furosemide (−41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis.
Stem bark of Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesic and anti-inflammatory activities. The analgesic activity was determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using Morphine sulphate as standard drug at a dose of 5 mg/kg of body weight and the results were expressed as mean increase in latency after drug administration ± SEM. The anti-inflammatory activity was assessed by Carrageenan-induced rat paw oedema using diclofenac sodium as standard drug at a dose of 100 mg/kg of body weight and expressed in terms of mean increase in paw volume ± SEM. Stem bark extract was given at a dose of 250 mg/kg and 500 mg/kg of body weight. Both standard drugs and extract were administered orally to the animals. Control received distilled water orally. Results showed that Nyctanthes arbor-tristis Linn. had potent analgesic and anti-inflammatory activities.
The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, fluid and electrolyte homeostasis. The RAS is activated and renal interstitial hydrostatic pressure (RIHP) is decreased in diabetic rats. The objective of this study was to evaluate the roles of proximal tubule reabsorption and RAS in the decreased RIHP and blunted natriuretic and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Enalapril was utilized to inhibit angiotensin II (AII) formation. Diabetes mellitus (DM) was induced by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 65 mg/kg). RIHP was measured by a polyethylene (PE) matrix that was chronically implanted in the left kidney. Fractional excretion of phosphate (FEPi) and fractional excretion of lithium (FELi) were used as indexes for proximal tubule reabsorption. VE significantly increased both FELi and FEPi in all groups of rats studied. However, the increase in FELi (ΔFELi=17.26±3.83%) and FEPi (ΔFEPi=7.38±2.37%) in diabetic rats (DC, n=12) were significantly lower as compared with those in nondiabetic control rats (NC, n=8; ΔFELi=32.15±4.71% and ΔFEPi=20.62±3.27%). The blunted increases in FELi and FEPi were associated with an attenuated increase in RIHP (ΔRIHP) in DC (1.8±0.4 mmHg) compared with NC rats (4.3±0.3 mmHg). Enalapril treatment (25 mg/kg/day in drinking water) had no effect on nondiabetic rats (NE, n=8) as compared with untreated NC rats, but significantly improved RIHP response (ΔRIHP) to VE in diabetic rats (DE, n=9; 2.8± 0.5 mmHg). Both FELi and FEPi were restored by enalapril treatment in diabetic rats and no significant differences were found in ΔFELi and ΔFEPi between DE (ΔFELi=26.81±4.94% and ΔFEPi=10.45±4.67%) and NC groups of rats in response to VE. These data suggest that the activated RAS and the decrease in RIHP may play an important role in the increased proximal tubule reabsorption, and the attenuated natriuretic and diuretic responses to acute volume expansion in diabetic rats.
Diabetes mellitus; Renin-angiotensin system; Renal interstitial hydrostatic pressure; Volume expansion; Proximal tubule reabsorption
A natriuretic and diuretic response to whole blood infusion in the rat, exaggerated and sustained by intravenous reinfusion of excreted urine, was shown to be associated with increased glomerular filtration and reduced tubular reabsorption. Cross-circulation of animals so responding (donor rats) with isovolemic recipients led to a modest natriuretic and diuretic response in the latter, not accounted for by altered physical composition of the blood nor by observed changes in filtration rate or arterial blood pressure. The recipient natriuresis was unchanged when nephrectomized donors were used and it occurred in experiments in which donor urine was simultaneously replaced by intravenously infused Ringer-Locke solution; the natriuretic property of the cross-circulating blood could therefore not have been due to reinfusion of urinary constituents, nor to accumulation of metabolites, nor to a factor of renal origin. A recipient natriuresis was also observed when the expanded and urine reinfused donor had been acutely adrenalectomized, ruling out an altered secretion of adrenal cortical or medullary hormones as a principal cause of this natriuresis; the data, however, do not exclude participation of reduced aldosterone secretion in the normal effector mechanism. In control experiments in which whole blood was exchanged for donor blood, a small delayed natriuresis did occur in the recipient; this could be completely prevented by administration of aldosterone. In similar exchange experiments with adrenalectomized donors, a small natriuresis developed in the recipient before blood administration but declined afterwards. These minor natriuretic effects probably resulted from altered mineralocorticoid content of the cross-circulating blood due to factors other than blood volume change. The larger natriuretic response seen in all recipients when the donor was volume expanded must have been due largely to a humoral natriuretic factor of other than renal or adrenal origin.