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Biomedical subjects

I Serban

Publications and source records attributed to I Serban.

At least 19 recordsLinked to original sources
PubMed1994

Role of nitric oxide (EDRF) in radiocontrast acute renal failure in rats.

This study was undertaken to examine the possible role of endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), in the pathogenesis of radiocontrast-induced acute renal failure in rats. Normal and salt-depleted rats were monitored for 60 min or 24 h after radiocontrast administration. The administration of L-arginine to normal rats abolished the immediate decrease in p-aminohippurate clearance (CPAH) and attenuated the decrease in inulin clearance (CIn). The administration of NO synthase inhibitor to the salt-depleted animals resulted in a significantly more pronounced decrease in CPAH compared with both the control and the L-arginine-treated animals. The recovery of CIn 24 h after radiocontrast administration to the salt-depleted rats was significantly better in the L-arginine-treated rats than in either the control or inhibitor-treated groups. The administration of radiocontrast material resulted in a significant decrease in urinary guanosine 3',5'-cyclic monophosphate as well as NO2 + NO3 excretion. This decrease was significantly attenuated by L-arginine. Our results 1) suggest that NO plays a major role in the pathogenesis of radiocontrast-induced acute renal failure and 2) suggest a novel therapeutic approach, i.e., the use of L-arginine in this form of acute renal failure.

Acute Kidney Injury↗
PubMed1994

Effect of chronic cholesterol loading in the development of acute ischemic renal failure in rats.

The effect of chronic cholesterol loading and lovastatin administration in renal artery clamping acute renal failure in rats is not known. Acute renal failure was induced by 60-min left renal artery clamping immediately after right nephrectomy. The changes in renal function after renal artery clamping in the hyperlipidemic rats were unexpected. The acute renal failure in the cholesterol-loaded groups was less severe than in the nonhyperlipidemic rats. The lovastatin administration had some favorable effect on renal function after ischemia; however, this effect was not additive to the high dietary cholesterol administration. Our results seems to favor the concept that in this special form of experimental renal ischemic acute renal failure, serum cholesterol levels, elevated through diet, may have protective effects with respect to renal tubular lesions during or following the acute ischemic insult.

Acute Kidney Injury↗
PubMed1994

Role of nitric oxide in glycerol-induced acute renal failure in rats.

EDRF results from the metabolism of L-arginine. N-omega-nitro-L-arginine is a nitric oxide synthase inhibitor (L-arginine competitive inhibitor). Acute renal failure was induced by i.m glycerol (50%) 5 ml/kg bw. L-arginine: 3 mg/kg bw/min for 60 min before and 60 min after glycerol administration. L-arginine inhibitor (150 micrograms/kg bw/min for 120 min). Cin, Cpah and FENa% were measured immediately or 24 h after glycerol (mean of three periods of 20 min). A second series of similar experiments was done in dehydrated (16 h) rats with a high dose of glycerol (50% solution, 10 ml/kg bw). L-arginine ameliorates the severity of ARF immediately after glycerol administration and enhances the recovery of glycerol-induced ARF. The L-arginine inhibitor resulted in a more severe ARF. Urinary cGMP decreased significantly after glycerol administration. It is concluded that nitric oxide has an important pathogenetic role in the glycerol induced ARF.

Acute Kidney Injury↗
PubMed1993

Experimental uremia in male rats: effect on the reproductive tract and fertility.

Chronic renal failure was induced in 3-month-old male rats by 5/6 nephrectomy. Potency and fertility studies were performed after 3 months of chronic uremia. The mean serum testosterone at the end of the experiments was significantly lower: 0.96 +/- 0.14 ng/mL compared to a control group of sham-operated male rats, 2.86 +/- 0.59 ng/mL, p < .001. All the uremic male rats had normal accessory gland weights at the end of the study. Fertility and, in most animals, sexual behavior and mating were not different from the normal control group. It is concluded that in 5/6-nephrectomized uremic male rats, in spite of low testosterone level, fertility and reproductive system are maintained similar to normal control male rats.

Animals↗
PubMed1993

Effect of verapamil on disposition of intravenous potassium in diabetic anephric uremic rats.

Calcium channel blockers decrease the plasma potassium concentration in acutely nephrectomized rats exposed to an acute potassium load. We examined the effect of verapamil on the plasma potassium concentration during an acute potassium load in anephric-uremic diabetic and non-diabetic rats. The plasma potassium concentration was measured at 15-min intervals during 60 min of continuous KCl infusion, with and without verapamil. The baseline potassium concentrations were higher in diabetic rats vs. nondiabetic controls. Verapamil blunted the increase in plasma potassium in diabetic and nondiabetic rats compared with the respective controls. The pH and hematocrit were similar in all groups. We conclude that the effect of verapamil on extrarenal potassium disposal are independent of insulin and the renin angiotensin system in the uremic state.

Animals↗
PubMed1992

Early diagnosis of gram-negative peritonitis in continuous ambulatory peritoneal dialysis patients with the Lymulus amebocyte lysate assay.

The treatment of peritonitis in continuous ambulatory peritoneal dialysis patients is empiric until the bacteriological results are available. The Lymulus amebocyte lysate assay (LAL) is a very sensitive method for the detection of endotoxin, a structural component of gram-negative bacteria. We performed the LAL assay in a prospective study in 36 consecutive episodes of peritonitis. The LAL assay was positive in all 10 episodes of gram-negative peritonitis (100% specificity). Treatment directed specifically against gram-negative or -positive infection was started based on the LAL assay result. In 26 episodes with LAL-negative test, a gram-positive bacterium was cultured in 23 episodes, in 1 there was fungal infection and 2 were sterile. In summary: the LAL assay is a rapid (1 h) and sensitive method for the differentiation of gram-positive or -negative peritonitis and enables starting an immediate and more appropriate antibiotic therapy.

Endotoxins↗
PubMed1988

The calcium channel blocker nisoldipine delays progression of chronic renal failure in humans (preliminary communication).

Chronic renal failure (CRF) patients with a stable course were asked to participate in a follow-up program in which they were randomized into two groups: 1) the placebo group taking their standard antihypertensive therapy without any calcium ion blocker: and 2) the nisoldipine group, those patients taking the calcium channel blocker nisoldipine as the only antihypertensive drug. The two groups had similar blood pressures on entering the study (151 +/- 21.3/90.7 +/- 7.4 mmHg in the nisoldipine and 146.7 +/- 18/94 +/- 9.4 mmHg in the placebo group). Their protein intake was also similar (daily average throughout the follow-up period: 0.83 +/- 0.18 g protein per kg body weight in the nisoldipine and 0.9 +/- 0.12 g in the placebo group). The patients were checked monthly. The follow-up averaged 11.1 +/- 4.8 months in the nisoldipine group and 13.7 +/- 4.2 months in the placebo group. The rate of progression of CRF, as expressed by the slope of the regression line of 1/serum creatinine versus time, decreased in the nisoldipine group from the initial (-8.03 +/- 4.91) x 10(-3) to (-5.57 +/- 5) x 10(-3) (two-tailed P-test = 0.016) after intervention. The slopes tended to become steeper in the placebo group, with an initial slope of (-4.1 +/- 3.2) x 10(-3) changing to (-7.9 +/- 5) x 10(-3) after intervention. This difference did not reach statistical significance (two-tailed P = 0.072). The rate of progression of CRF decreased in 12 of 14 patients in the nisoldipine-treated group versus 3 of 11 patients in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The control of hypertension and its effect on renal function in rat remnant kidney.

Blood pressure control and its influence on the rat remnant kidney function were studied. The deterioration in kidney function was followed for up to 20 weeks at 4-weekly intervals in four groups of 5/6th nephrectomised rats. The groups studied were: (1) Control, untreated (C), given normal rat chow containing 21% protein; (2) nisoldipine (a dihydropyridine calcium channel blocker) treated (N), given nisoldipine freshly mixed daily in normal chow (0.3-0.6 mg/kg body weight); (3) dihydralazine-treated (H), fed normal chow and given dihydralazine added daily to the drinking water, about 15-25 mg/kg body weight daily; and (4) low-protein (6%) diet (LP), isocaloric and having the same sodium content as the normal chow. Proteinuria, serum creatinine, blood urea, histological damage as seen by light microscopy, and cumulative survival were taken to assess the severity of the chronic renal failure. All three therapeutic regimens attenuated significantly the rise in blood pressure which developed within less than 4 weeks in the rats with the remnant kidney. At the 16th week, means +/- standard deviations were, in group C, 237 +/- 20 mmHg; group N, 147 +/- 20 mmHg; group H, 164 +/- 23 mmHg; and group LP 149 +/- 16. Systolic blood pressure at the 8th week had a significant correlation with the serum creatinine of the 12th and of the 16th weeks. There was a strong correlation between blood pressure and the serum creatinine at the 16th week. This indicates that a time lag is necessary for the hypertension to have an effect on kidney function. Proteinuria, serum creatinine and blood urea were much higher in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Relationship between plasma renin activity and distal nephron sodium delivery and reabsorption in man.

The relationship between plasma renin activity and distal tubular sodium delivery and reabsorption was examined in man. Distal sodium delivery and reabsorption were measured during hypotonic volume expansion by the free water clearance method, or during hydropenia or isotonic volume expansion by the lithium clearance method. The maximal water diuresis method and the lithium clearance method both showed a negative correlation between plasma renin activity and distal sodium delivery and reabsorption. Only with the lithium clearance method, however, was it possible to measure plasma renin activity, distal sodium delivery and reabsorption in hydropenia without disturbances of water and electrolyte balance and plasma renin activity level. In hydropenia the plasma renin activity was higher and the fractional distal sodium delivery and reabsorption lower than during volume expansion. Our results support the idea that sodium chloride reabsorption at the macula densa region is negatively correlated to the plasma renin activity in man.

Absorption↗
PubMed1986

Calcium entry-blockade with verapamil in cyclosporine A plus ischemia induced acute renal failure in rats.

The possible alleviating effect of verapamil, a calcium entry blocker, on the resulting renal damage from the combination of a short episode of ischemia and CyA was studied in rats. Immediately after right nephrectomy the rats were divided into five experimental groups. Group 1: left renal pedicle clamping for 20 minutes. Group 2: as group 1 plus CyA 60 mg/kg bw i.p. Group 3: CyA as in group 2 but sham operated. Group 4: as group 2 plus verapamil 10 mg% in the drinking water. Group 5: as group 3 plus verapamil given as in group 4. The experiments lasted 4 days. By analysis of variance: CyA + ischemia (group 2) showed lower creatinine clearance (p less than 0.001), higher blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.05) and fractional excretion of potassium (p less than 0.01) and fractional excretion of negative free water clearance (p less than 0.001) compared to ischemia alone (group 1). The CyA + ischemia rats treated with verapamil had higher creatinine clearance (p less than 0.05), lower blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.001), fractional excretion of potassium (p less than 0.001) and fractional excretion of negative free water clearance (p less than 0.05) compared with the untreated verapamil CyA + ischemia group. The CyA + sham operated verapamil treated group had similar creatinine clearance with the corresponding verapamil untreated group. The CyA + ischemia group had the higher mean daily body weight reduction compared with all other groups. Histology showed more vacuolization of tubular epithelial cells in the CyA + ischemia than in ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1985

Beta-adrenergic receptors on polymorphonuclear cell membranes in essential hypertension.

Beta adrenergic receptor binding sites were determined and characterized by specific binding of (+/-)[125I] iodocyanopindolol to membranes obtained from circulating polymorphonuclear leukocytes. No difference was found in the number of receptor sites and in their dissociation constants (Kd) between patients with untreated essential hypertension (EH), EH treated with drugs other than beta blockers, and in normotensive controls. The group with EH receiving treatment with beta blockers had a significantly higher receptor density and Kd as compared with all the other groups (p less than 0.05). It is concluded that the beta-adrenergic system of patients with essential hypertension at the receptor level is not different from normotensive subjects and responds to beta blockers by up-regulation.

Adult↗
PubMed1985

Cyclosporine and short ischaemia: a new model of experimental acute renal failure in rats.

To determine whether a mild episode of ischaemia may be a factor in the production of cyclosporine (Cys) toxicity, right nephrectomy was performed in three groups of Charles River rats: I. Ischaemia (left renal pedicle clamping) for 20 minutes, without treatment; II. Ischaemia of 20 minutes, followed by IP Cys 60 mg/kg BW/day; III. Sham (no ischaemia) followed by Cys as in Group II. The rats were sacrificed after four days. Cys plus ischaemia produced a lower creatinine clearance (136 +/- 15 microliter/min/100g BW, p less than 0.001) and a higher FENa per cent (0.94 +/- 0.14, p less than 0.05), FEK (1.07 +/- 0.02, p less than 0.01) compared with ischaemia alone creatinine clearance 261 +/- 39, FENa per cent 0.61 +/- 0.08, FEK 0.54 +/- 0.08, FEH2O -0.04 +/- 0.005. Histology showed more vacuolisation of tubular epithelial cells in the Cys plus ischaemia group than in the ischaemia alone group.

Acute Kidney Injury↗
PubMed1984

Calcium-entry blockade and pressor effect of angiotensin II in normal and nephrectomized rats.

The pressor effect of intravascular boli of 1.5 micrograms/kg angiotensin II was studied in untreated and in verapamil-pretreated intact rats and in rats 24 h after bilateral nephrectomy. An initial i.v. dose of 250 micrograms/kg verapamil was followed by a continuous infusion of 7 micrograms/min per kg. This resulted, within 2 min, in an average decrease in mean arterial pressure of 19 +/- 3 (SE) mm Hg and 18 +/- 3 (SE) mm Hg in intact and bilaterally nephrectomized rats, respectively. This continuous dose of verapamil did not significantly prevent the pressor effect of angiotensin II. When the continuous infusion of verapamil was increased to 50 micrograms/min per kg, the rise in blood pressure following angiotensin II administration was significantly lower than in the untreated rats: 21 +/- 2 (SE) mm Hg in intact rats, compared with 39 +/- 3 (SE) mm Hg (P less than 0.001) in the untreated animals and 31 +/- 3 (SE) mm Hg in rats in the renoprival state, compared with 47 +/- 6 (SE) mm Hg (P less than 0.01) in the corresponding untreated group. The present study suggests that verapamil can be used as a calcium blocker to reduce blood pressure associated with, or caused by, an increased renin-angiotensin system activity.

Angiotensin II↗
PubMed1983

Beneficial effect of verapamil in ischemic acute renal failure in the rat.

To investigate the possible protective effect of Ca2+ blockers in ischemic acute renal failure (ARF), verapamil, in a dose of 10 micrograms/kg body wt/min was administered for 100 min, starting 15 min before the total occlusion of the left renal artery after right nephrectomy in rats. Mean 24-hr creatinine clearance, blood urea, and serum creatinine levels, 24 hr after declamping, were used as a measure of kidney function. These values which were 135 +/- 1.9 microliter/min, 231 +/- 22 mg%, and 2.25 +/- 0.22 mg%, respectively, in the untreated rats, were found to be significantly different, i.e., 326.3 +/- 33.2 microliter/min, P less than 0.001, 112 +/- 25 mg%, P less than 0.001, and 1.26 +/- 0.28 mg%, P less than 0.01, respectively, in the verapamil-treated animals. Increased 24-hr total urine creatinine, sodium, osmolality, and a lower fractional excretion of sodium were also observed in the verapamil-treated rats with ARF. The combination of propranolol 1 mg/kg body wt/min and verapamil 10 micrograms/kg body wt/min for 100 min had no additive effect on renal function. In another group of ARF rats in which verapamil was started after declamping, no alleviating effect was observed. It is concluded that verapamil, an inhibitor of cellular membrane transport, when given prior to the renal ischemia, offers a partial but significant protection in this model of ischemic ARF.

Acute Kidney Injury↗
PubMed1982

Lithium prevents saline deoxycorticosterone acetate (DOCA) hypertension in the rat.

Uni-nephrectomized rats drinking 1% saline instead of water, were given Doca intramuscularly, 50 mg/kg BW per week for 2 weeks. The mean blood pressure in the control group was 105 +/- 4 (+/- S.E.) mm Hg, whereas in the Doca-saline group it rose to 152 +/- 5.1 (p less than 0.001). Rats, similarly treated, were placed on daily intraperitoneal lithium injections of either of two doses: 1.5 or 3.0 mEq/kg BW per day. Their blood pressures, at the end of 2 weeks of treatment, were 117 +/- 2 mm Hg and 103 +/- 2.1, respectively (p less than 0.001 vs. lithium-untreated Doca-saline rats). Water-drinking rats, receiving daily intraperitoneal lithium (3 mEq/kg BW) for 2 weeks, had normal blood pressures, not different from the controls (104 +/- 11 mm Hg). The Doca-saline and Doca-saline-lithium (1.5 mEq/kg/day) groups had similar changes in mean daily body weight, plasma sodium, osmolality, and GFR. The renal beta-adrenergic receptor density in the Doca-saline-lithium rats was in the normal range, 51 +/- 4.5 mol/mg of protein. In the Doca-saline hypertensive rats, it was significantly lower, being 27.2 +/- 3 fmol/mg of protein, p less than 0.05. These renal plasma cell membrane beta-adrenergic receptors were characterized by direct tissue binding with (-)[3H]dihydroalprenolol. These results show that lithium prevents the development of hypertension in the Doca-saline rats. The effect of lithium on the sympathetic nervous system is a possible mechanism in the prevention of the Doca-saline hypertension.

Animals↗
PubMed1980

beta 1-Adrenergic receptors in kidney tubular cell membrane in the rat.

We used a beta-adrenergic antagonist, (-) 3H-dihydroalprenolol, to demonstrate binding sites in purified rat kidney preparations that consistsed of plasma membranes of cells from tubules. The tubular origin of these plasma membranes was shown by electron microscopy and Na-K-ATPase enrichment. The binding was rapid (t1/2, 78 sec) and rapidly reversible (t1/2, 48 sec). The binding sites were saturable and bound 69.8 +/- (SD) 29.1 fmoles/mg of membrane protein. The binding was stereospecific with the isomers of beta-adrenergic agonists and beta-adrenergic antagonist propranolol, the (-) isomers being about 40 times more potent than the (+) isomers incompeting for these sites. (-) 3H-dihydroalprenolol had a high affinity for the binding sites, expressed by the mean equilibrium dissociation constant (KD) (KD, 7.1 nM). The beta-adrenergic antagonist (-) propranolol also showed high affinity (KD, 62.8 nM). The order of potency for inhibition of binding by beta-adrenergic agonists was: (-) isoproterenol (KD, 0.66 microM) greater than (-) epinephrine (KD, 4.3 microM) greater than or equal to (-) norepinephrine (KD, 13.5 microM). Conclusion. The (-) 3H-dihydroalprenolol binding sites in the rat kidney tubular cell membrane are beta-adrenergic receptor of the beta1 subgroup.

Alprenolol↗