Constant-infusion technique of inulin clearance without urine collection

Inulin clearance is accepted as the gold standard for estimating the glomerular filtration rate (GFR). However, the method of this examination is troublesome and infants need difficult bladder catheterization. The existence of residual urine results in an inaccurate estimation of GFR and the proceduse requires a large amount of transfusion. In the plasma infusion method, inulin reaches an equilibrium in which the inulin urinary excretion rate is equal to the infusion rate, and urine collection is unnecessary. We estimated GFR in 21 children using both the plasma infusion method and renal infusion method. In the renal infusion method, the loading infusion of 1% inulin was administered over 30 minutes at the dose of 5 mL/kg body weight, followed by maintenance infusion at the constant speed (mL/hour) of 1.5 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/ 1.73. Three 30-minute urine collections were performed and the plasma inulin levels were measured to estimate GFR. In the plasma infusion method, maintenance infusion was conducted at the speed (mL/hour) of 0.6 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/1.73. The mean plasma inulin concentrations at 8, 9 and 10 hours were examined and GFR was calculated with the infusion rate. The GFRs for the renal infusion methods (Cin) and plasma infusion methods (e-Cin) were 91.90 +/- 39.61 and 95.33 +/- 38.08 mL/min/1.73 m2, respectively. The values for Cin and e-Cin showed good linear correlation (R2 = 0.81). The value of e-Cin/Cin was 1.069 +/- 0.172 and the mean e-Cin value was only 7% higher than that of Cin. We believe that GFR estimated by the constant infusion method shows a value approximating that estimated by the standard method. This technique is noninvasive for infants and the GFR of children who have vesicoureteral reflux or residual urine in the bladder can be estimated. The method does not need a large amount of transfusion and is suitable for children with heart failure. We believe that this method is clinically useful.     

Effects of docarpamine on hemodynamics after open heart surgery in children.

Docarpamine is a dopamine prodrug which has been selected from a large number of dopamine derivatives in order to develop an orally effective dopamine. The pharmacokinetics after oral administration of docarpamine have not yet been studied in children undergoing open heart surgery. This study examined the effects of docarpamine on hemodynamics and evaluated its safety in 11 children undergoing open heart surgery for congenital heart disease. This study began when the patientOs postoperative condition was stabilized by continuous dopamine infusion into the vein at a rate of 5 micro g/kg/min. The patients were administered 40 mg/kg of docarpamine every 8 hours, and hemodynamics were measured every 4 hours for 16 hours after the initial docarpamine administration. Immediately after the initial docarpamine administration, the dose of dopamine was reduced to 3 micro g/kg/min. Infusion of dopamine was stopped 8 hours after the initial docarpamine administration. Systemic systolic and diastolic blood pressure and heart rate showed no significant changes. Mean right atrial pressure decreased 4 hours after docarpamine administration. Mixed venous oxygen saturation and mean velocity of circumferential fiber shortening increased significantly after docarpamine administration. No significant changes were observed in urine volume. All patients could be weaned from dopamine within 8 hours. No changes were observed in ECG, and no arrhythmia-inducing action was noted. Our study indicates that 40 mg/kg oral doses of docarpamine produce plasma dopamine concentration equivalent to those of a 3 to 5 micro g/kg/min dopamine infusion. Our data suggest that docarpamine is a safe and effective drug for children who have undergone open heart surgery.     

Renal effects of low to moderate doses of dopamine in newborn piglets.

PURPOSE: Administration of dopamine to adult animal and human subjects results in increased renal blood flow, and it may also enhance the glomerular filtration rate. However, renal hemodynamic effects of exogenous dopamine in the neonate are unclear. In this study, we examined the renal actions of low to moderate doses of exogenous dopamine in newborn piglets. METHODS: The animals were anesthetized, catheterized for vascular access and urine collection, and assigned randomly to a control group or treatment groups receiving dopamine infusion at 2, 5, or 10 microg/kg/min. Data were collected at baseline, during dopamine infusion, and 1 hour after cessation of infusion. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored. Glomerular filtration rate (GFR), cardiac index (CI), and renal blood flow (RBF) were determined. Fractional excretion of sodium (FENa) was calculated. RESULTS: Dopamine did not alter renal blood flow nor did it significantly alter CI in spite of a modest increase in heart rate and mean arterial blood pressure. There was a statistically significant increase in GFR at 10 microg/kg/min and in FENa at all doses. CONCLUSIONS: Low doses of dopamine produce significant natriuresis probably by direct action on renal tubules and at moderate doses via, both, increase in GFR and a direct tubular effect. Low and moderate doses of dopamine do not increase RBF as seen in adult animals, possibly because of immaturity of dopaminergic receptors in newborn piglets.     

Renal and hemodynamic effects of dopamine in infants following cardiac surgery

The renal and hemodynamic effects of dopamine were measured during the immediate postoperative period in six infants following repair of congenital cardiac defects. Dopamine was infused at rates of 5, 10, and 15 micrograms/kg/min. Cardiac index (CI) increased significantly at a dopamine infusion rate of 15 micrograms/kg/min. The glomerular filtration rate (GFR) and urine output increased at dopamine infusion rates of 5 and 10 micrograms/kg/min and returned to baseline at 15 micrograms/kg/min. No significant changes occurred in right atrial pressure (RAP), left atrial pressure (LAP), systemic artery pressure, systemic vascular resistance (SVR), or pulmonary vascular resistance (PVR). Heart rate (HR) increased slightly at a dopamine infusion rate of 15 micrograms/kg/min. Pulmonary artery pressure (PAP) increased significantly in only one patient. These data demonstrate that infants require high doses of dopamine to produce the hemodynamic effects seen in adults and that these higher doses may be used without adverse renal effects.     

The Hemodynamic Effects of Dopamine Following Cardiopulmonary Bypass

The hemodynamic effects of dopamine were studied in 19 patients following intracardiac operation or myocardial revascularization using extracorporeal circulation. The heart rate, mean blood pressure, central venous pressure, left atrial and pulmonary artery pressures, cardiac output, and urine output were recorded before and at the end of one-hour infusions of dopamine at 5,10, and 15 μg/ kg/min. Infusion of 5μg/kg/min of dopamine resulted in the highest gain in cardiac output and stroke work without an increase in myocardial oxygen consumption, as evidenced by lack of significant rise in heart rate. In addition, this dosage was not accompanied by an increase in pulmonary or systemic vascular resistance, nor were other untoward effects observed after administration of 5 μg/kg/min of dopamine.     

Comparison of Dopamine and Dobutamine Following Coronary Artery Bypass Grafting

A prospective, randomized comparison of the hemodynamic effects of dopamine and dobutamine was performed in 20 patients following coronary artery bypass grafting. Approximately 6 hours postoperatively, when patients were hemodynamically stable, either dopamine or dobutamine was administered at 2.5, 5.0, and 7.5 μg per kilogram of body weight per minute. At 5.0 μg/kg, both drugs increased cardiac index without changing heart rate, mean arterial pressure, pulmonary capillary wedge pressure, or peripheral vascular resistance. At 7.5 μg/kg, dobutamine caused a further increase in cardiac index without changing the other variables. In contrast, increasing dopamine from 5.0 to 7.5 μg/kg/min caused significant increases in mean arterial pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance but no further increase in cardiac index. We conclude that dobutamine is preferable to dopamine in patients following coronary artery bypass grafting, since it produces consistent, dose-related increases in cardiac index without increases in heart rate, mean arterial pressure, pulmonary capillary wedge pressure, or pulmonary vascular resistance.     

Dopamine versus Dobutamine after Open-Heart Surgery

The haemodynamic effects of dopamine and dobutamine were compared in a cross-over study of 12 patients in the early postoperative phase after open-heart surgery. The drug infusion rates (dopamine (μg/kg/min) mean 6.5, range 2.8–12, dobutamine (μg/kg/min) mean 7.9, range 4.3–12.3) were adjusted so that the cardiac output increased by 50%. With both drugs this was achieved through simultaneous increases in stroke volume (dopamine + 16%, dobutamine + 9%) and heart rate (dopamine + 31 %, dobutamine + 38%). The systemic vascular resistance did not change with dopamine but decreased significantly (—18%) with dobutamine. Therefore, the systolic and diastolic arterial blood pressures rose significantly more with dopamine than with dobutamine. The left atrial pressure increased with dopamine but was unchanged with dobutamine. The urine output was significantly higher with dopamine than with dobutamine.     

Measurement of renal functional reserve of the single kidney in man

The renal functional reserve capacity (RFRC) and response of the single kidney to a low protein diet (LPD) were investigated. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured using a single injection of I125 Hippuran and Cr51 EDTA during a dopamine infusion (3 micrograms/kg/min) and after 2 weeks on a LPD (0.6 g/kg/day). Dopamine increased ERPF but the associated rise in GFR was not significant. There was a significant decrease in both ERPF and GFR on LPD. The change in GFR during dopamine infusion, but not during LPD, correlated inversely with baseline GFR. Dopamine and LPD had no effect on heart rate or blood pressure and LPD did not alter urinary sodium excretion. These results suggest that the single kidney lacks functional reserve capacity and that protein restriction may be useful in preserving long term function.     

Selective endothelin B receptor blockade does not influence BNP-induced natriuresis in man

Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) both exhibit natriuretic activity within the human kidney. Furthermore, they both act partly through activation of the endothelial nitric oxide pathway. Since ET-1 may cause vasodilation and natriuresis via stimulation of the ET-B receptor, the aim of the present study was to investigate whether renal ET-B receptors participate in the renal actions of BNP. In this placebo-controlled, crossover study, we infused BNP (4 pmol/kg/min) or placebo (i.v.) for 1 h, with or without co-infusion of the ET-B receptor antagonist BQ-788 (50 nmol/min) for 15 min on 4 separate days, in 10 healthy subjects (mean age 54+/-6 years.). During infusion, we measured effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) using PAH/inulin clearance. Cardiac output was measured before and after infusion, using echocardiography. Blood pressure and heart rate (HR) were monitored as well. Urine and plasma samples were taken every hour to measure diuresis, natriuresis, cyclic 3',5' guanosine monophosphate, and ET-1 levels. BNP with or without ET-B receptor blockade increased natriuresis and diuresis. In addition, BNP alone increased GFR and filtered load, without changing ERPF. BQ-788 infusion did not affect renal hemodynamics or natriuresis. Neither BNP nor BQ-788 altered cardiac output, blood pressure, and heart rate. In conclusion, the present study shows that selective ET-B receptor blockade has no effect on the BNP-induced natriuresis and glomerular filtration rate.     

Effect of exogenous ANP on initial renal function following 24-hour cold preservation

The impact of synthetic atrial natriuretic peptide (sANP) on renal function following cold ischemic injury was studied in a canine autotransplant model. Following a prenephrectomy inulin clearance determination (CIn), the left kidney was excised, flushed with Eurocollins solution, and cold-stored for 24 hours. Immediately following reperfusion and a 10 minute equilibration period, baseline CIn was measured over a 20-minute time interval (Collection Period I). Experimental animals (N = 11) then received 1 mcg/kg sANP by intravenous bolus followed by a continuous infusion at 0.3 mcg/kg/min for 30 minutes. CIn was measured throughout the infusion (Collection Period II). Normal saline was substituted for sANP in control animals (N = 11). CIn was also measured 24 hours following reimplantation in seven control and seven sANP-treated animals. Autograft inulin clearance increased from 0.32 +/- 0.11 ml/min during Period I to 2.5 +/- 0.6 ml/min during sANP infusion (P less than 0.01). This increase in CIn associated with ANP infusion was accompanied by increases in urine flow rate (V) (0.15 +/- 0.05 ml/min to 0.98 +/- 0.21 ml/min, P less than 0.01) and renal blood flow (RBF) measured by electromagnetic flow probe (85 +/- 17 ml/min to 171 +/- 13 ml/min, P less than 0.05). No significant changes in CIn, V, or RBF occurred in control animals between periods I and II. Although systemic blood pressure declined during sANP infusion, it did not decrease to an extent that compromised peripheral perfusion. CIn determined 24 hours after autograft reimplantation in the ANP-treated animals approximated or exceeded values determined during ANP infusion (Period II).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of combined dopamine and bunazosin on the ischemic heart after occlusion of the coronary artery

In order to investigate whether dopamine combined with bunazosin improves cardiac function, the global and regional cardiac function and regional blood flow of 7 anesthetized dogs were analyzed before and after occlusion of the left anterior descending coronary artery (LAD), then after 10 micrograms/kg/min dopamine infusion following the LAD occlusion, and again after a bolus infusion of bunazosin 250 micrograms/kg. Dopamine with bunazosin reduced left atrial pressure from 4.9 +/- 0.9 to 3.1 +/- 0.5 mmHg (p less than 0.05) and improved cardiac output from 1.22 +/- 0.15 to 1.50 +/- 0.14 L/min (p less than 0.05), maximum positive left ventricular dp/dt from 1721 +/- 202 to 3600 +/- 663 mmHg/sec (p less than 0.05) and the time constant from 45.2 +/- 5.0 to 27.5 +/- 4.6 msec (p less than 0.01). Bunazosin added to the dopamine reduced the elevated left ventricular peak systolic pressure caused by dopamine from 130 +/- 7 to 113 +/- 8 mmHg (p less than 0.01). With regard to the regional wall motion, the impaired LAD-delta L (the segment systolic shortening) and LAD-Elmax (the slope of peak systolic pressure--endsystolic length relation) following the LAD occlusion improved from 0.5 +/- 2.5 per cent to 5.9 +/- 2.6 per cent (p less than 0.01) and from 50 +/- 9 to 82 +/- 14 mmHg/mm (p less than 0.01) after the infusion of dopamine with bunazosin. Dopamine greatly increased the Rate Pressure Product (RPP) from 12610 +/- 1120 after LAD occlusion to 16950 +/- 1420, whereas dopamine in combination with bunazosin did not increase the RPP due to a drop of LV-PSP with little change in regional myocardial blood flow. It was concluded that combining dopamine with bunazosin was useful for improving both the global and regional cardiac functions of the ischemic heart.     

Effect of L-dopa decarboxylase inhibitor benserazide on renal function in streptozotocin-diabetic rats

BACKGROUND/AIMS: Benserazide (BZD), an inhibitor of the dopamine synthesis, abolished the increase in glomerular filtration rate (GFR) following the infusion of a mixed amino acid solution. These results reveal endogenous dopamine as a mediator in the renal response to amino acids. The aim of the present study was to evaluate whether dopamine is also involved in the regulation of glomerular hyperfiltration during the early state of diabetes mellitus (DM). METHODS: Male Sprague-Dawley rats were injected with a single dose of streptozotocin (60 mg/kg i.p.) for induction of experimental DM (n = 7-8/group). Age-matched non-diabetic animals, injected with citrate buffer, served as controls (CON, n = 8/group). Clearance experiments were performed 2 weeks after induction of DM in thiopental-anesthetized rats (80 mg/kg i.p.), which were continuously infused either with BZD (30 microg/min/kg) or vehicle (VHC). RESULTS: Mean arterial blood pressure was around 110 mm Hg and did not significantly differ among the groups. GFR was 0.95 +/- 0.02 ml/min/100 g b.w. in VHC-treated CON. BZD treatment did not significantly change GFR in the CON group (0.92 +/- 0.06 ml/min/100 g b.w.). As expected, glomerular hyperfiltration was observed in diabetic rats infused with VHC (1.24 +/- 0.08 ml/min/100 g b.w.). Treatment with BZD significantly reduced the diabetes-induced increase in GFR to control levels (0.95 +/- 0.05 ml/min/100 g b.w.). CONCLUSION: Our results show that the inhibition of dopamine synthesis prevented the increase in GFR due to diabetic conditions, indicating that endogenous dopamine is involved in the regulation of DM-induced changes in renal hemodynamics.     

Opposing effects of angiotensin II on muscle and renal blood flow under euglycemic conditions

Angiotensin II (Ang II) enhances insulin sensitivity in humans, and this is associated with a paradoxical increase in skeletal muscle blood flow. It is unclear whether these effects are mediated via subtype 1 receptors of Ang II, because these receptors are thought to mediate vasoconstriction. Insulin-stimulated glucose uptake (euglycemic clamp technique) and leg muscle blood flow (plethysmography) were measured in nine healthy male volunteers (mean age, 24 +/- 2 yr) on three occasions using a double-blind, placebo-controlled study design. The subjects were allocated in random order to (1) placebo premedication per os plus placebo infusion, (2) placebo premedication per os plus infusion of 5 ng Ang II/kg per min, and (3) premedication with 300 mg of the angiotensin II-1-receptor antagonist irbesartan per os plus infusion of 5 ng Ang II/kg per min. In addition, GFR and effective renal plasma flow were assessed using the steady-state inulin- and paraaminohippurate clearance. Insulin sensitivity (i.e., M value) and muscle blood flow after infusion of Ang II (9.3 +/- 1.8 mg/kg per min; 17.7 +/- 2.1 ml/100 g per min) were significantly higher than after placebo infusion (7.2 +/- 1.6 mg/kg per min, P: < 0.02; 13.5 +/- 1.8 ml/100 g per min, P: < 0.01). In contrast, after premedication with irbesartan, they were not significantly different (7.5 +/- 1.7 mg/kg per min; 14.3 +/- 1.9 ml/100 g per min) as compared with placebo infusion. Mean GFR and effective renal plasma flow were significantly lower (P: < 0.01), and renal vascular resistance was significantly higher (P: < 0.01) with Ang II infusion as compared with the placebo infusion study. Premedication with irbesartan almost completely blocked the vasoconstrictive effect of Ang II on renal vasculature. Under hyperinsulinemic euglycemic conditions, infusion of Ang II has opposing effects on regional arterial blood flow, i.e., an increase in skeletal muscle blood flow, but vasoconstriction of renal vasculature. Both effects are antagonized by blockade of subtype 1 Ang II receptors.     

The effect of dopamine,atropine, phenylephrine and cardiac pacing on oxygen consumption during fentanyl-nitrous oxide anaesthesia in the dog

In animals deeply anaesthetized with fentanyl and nitrous oxide the artierial blood pressure and heart rate were increased using dopamine, atropine, electrical pacing and phenylephrine in order to study the accompanying change in whole body oxygen consumption. Seven dogs (16–24 kg) were anaesthetized with fentanyl 1 μg · kg^-1 · min^-1. After completing instrumentation a dopamine infusion was started at a rate of 39 μg · kg^-1 · min^-1. After the mean blood pressure reached 18.6 kPa the infusion was reduced to 10 μg · kg^-1 · min^-1 and maintained for 10 minutes. After waiting 45 minutes an infusion of atropine 20 μg · kg^-1 · min^-1 was started and when the heart rate reached 120 b/min the infusion was slowed to 1.25 μg · kg^-1 ’ · min^-1 and maintained for 10 minutes. Twenty-five minutes later the heart rate was increased to 150 beats/min and maintained at that level for 10 minutes using electrical pacing. The pacing was removed and an infusion of phenylephrine 5 μg·kg^-1·min^-1 was started. When the blood pressure reached 21.3 kPa the infusion was reduced to 2.5 μg · kg^-1· min^-1 and maintained for 10 minutes. The results show increases in oxygen consumption of 14 per cent with dopamine, 19 per cent with atropine, 16 per cent with pacing, and 14 per cent with phenylephrine. All changes were significantly different from the control values. The magnitude of change in whole body oxygen consumption was best predicted by either the cardiac output x blood pressure product or by the cardiac output alone.     

Diuretic response of a second infusion of atrial natriuretic polypeptide into anesthetized dogs

We examined the diuretic effects of a second infusion of atrial natriuretic polypeptide (ANP). Intrarenal infusion of ANP (50 ng X kg-1 X min-1) for 30 min to anesthetized dogs had no significant effect on mean arterial blood pressure (MABP), renal blood flow (RBF) and glomerular filtration rate (GFR), whereas there was an increase in urine flow (V) and urinary excretion of sodium (UNaV) from 7.5 +/- 1.5 to 34.1 +/- 9.4 microliters/g X min, from 0.97 +/- 0.20 to 4.38 +/- 1.32 microEq/g X min, respectively. When the same dose of ANP was infused 1 h after the first administration, V and UNaV were increased from 12.4 +/- 1.8 to 62.5 +/- 18.8 microliters/g X min, from 1.72 +/- 0.57 to 7.18 +/- 2.68 microEq/g X min, respectively. A second infusion of ANP caused a greater absolute increase in UNaV than did the first infusion but proportionally the increase in UNaV with the second ANP infusion was much the same. The present study shows that acute ANP infusion has no tachyphylaxis on the natriuretic response. These data will aid in establishing a bioassay for natriuretic response in vivo, thereby leading to elucidation of the physiological action of ANP.     

Renal function in mice: effects of volume expansion and angiotensin II

The present study was performed to validate a simple means for assessing renal function in anesthetized mice and to characterize the renal hemodynamic responses to acute volume expansion and how these responses are altered by concurrent angiotensin II (AngII) infusions. Inulin and para-aminohippurate clearances were used to assess GFR and renal plasma flow (RPF) in three groups of male C57Bl/6 mice anesthetized with inactin (100 mg/kg, intraperitoneally) and ketamine (10 mg/kg). To avoid the hypotension associated with repeated blood sampling, a single blood sample was taken after three timed urine collections. Renal function and mean arterial pressure (MAP) were measured under euvolemic conditions (2.5 microl/min, intravenously, n = 7) during isotonic saline volume expansion (12.5 microl/min, intravenously, n = 5) and during volume expansion with concurrent AngII infusion (5 ng/min x g, n = 5). MAP in the control group was 77 +/- 2 mmHg; volume expansion alone did not change MAP significantly (83 +/- 2 mmHg), but led to significantly greater values in both GFR and RPF (1.35 +/- 0.14 versus 1.01 +/- 0.1 ml/min x g and 11.26 +/- 1.39 versus 6.29 +/- 0.5 ml/min x g, respectively). Infusion of AngII during volume expansion led to significant elevations of MAP (100 +/- 3 mmHg, P < 0.05) and prevented the increases in GFR and RPF elicited by volume expansion (0.77 +/- 0.08 and 5.35 +/- 0.48 ml/min x g, respectively). Volume expansion also elicited marked increases in absolute and fractional sodium excretion (6.1 +/- 1.0 versus 0.62 +/- 0.2 microEq/min x g and 3.1 +/- 0.7 versus 0.4 +/- 0.1%, respectively). AngII infusion attenuated the absolute and fractional sodium excretion responses to volume expansion (3.4 +/- 1.2 microEq/min x g and 2.5 +/- 0.5%, respectively). The present findings demonstrate that anesthetized mice exhibit marked renal hemodynamic and excretory responses to isotonic saline volume expansion. Concomitant AngII infusion attenuates these responses in spite of greater increases in arterial pressure.     

Prophylactic Angiotensin II Infusion during Spinal Anesthesia for Elective Cesarean Delivery

Background: Angiotensin II may prove useful in treating regional anesthesia-induced hypotension in obstetric patients, because it causes less uterine vasoconstriction than do other vasoconstrictor drugs (such as phenylephrine). This study compared (1) maternal blood pressure and heart rate and (2) fetal status at delivery in parturients given either prophylactic angiotensin II or ephedrine infusion during spinal anesthesia for elective cesarean delivery.

Methods: Fifty-four women were randomized to receive either angiotensin II or ephedrine infusion intravenously during spinal anesthesia for elective cesarean section delivery. Simultaneous with subarachnoid injection, infusion of angiotensin II (2.5 [micro sign]g/ml) or ephedrine (5 mg/ml) was initiated at 10 ng [middle dot] kg-1 [middle dot] min-1 and 50 [micro sign]g [middle dot] kg-1 [middle dot] min-1, respectively. The rate of each infusion was adjusted to maintain maternal systolic blood pressure at 90-100% of baseline.

Results: Cumulative vasopressor doses (mean +/- SD) through 10, 20, and 30 min were 150 +/- 100, 310 +/- 180, and 500 +/- 320 ng/kg in the angiotensin group and 480 +/- 210, 660 +/- 390, and 790 +/- 640 [micro sign]g/kg in the ephedrine group. Maternal heart rate was significantly higher (P < 0.001) during vasopressor infusion in the ephedrine group than in the angiotensin group. Umbilical arterial and venous blood pH and base excess were all significantly higher (P < 0.05) in the angiotensin group than in the ephedrine group.     

A new procedure for evaluation of renal function without urine collection in rat

BACKGROUND: A new procedure to improve the accuracy of inulin assessment and renal glomerular filtration rate (GFR) avoiding urine sampling was compared and validated versus the reference procedure (with urine sampling and Anthrone reaction) in conscious unrestrained male Wistar rats. METHODS: The hemodynamic study consisted of a priming dose of inulin (16 mg/kg) and para-aminohippurate (PAH; 8 mg/kg) followed by an infusion of inulin (36 mg/mL) and PAH (5.8 mg/mL) at a rate of 0.055 mL/min until steady-state conditions were reached (105 min). Inulin concentrations from samples were determined by a new enzymatic assay and Anthrone reaction. PAH concentrations were determined according to the standard method described by Smith et al. RESULTS: A high correlation was found between GFR and renal blood flow (RBF) values calculated using the alternative (without urine sampling) and the reference (with urine sampling) clearance techniques (r = 0.98, P < 0.001, and r = 0.97, P < 0.001, respectively). Moreover, a significant and positive correlation between the values obtained from enzymatic and Anthrone inulin assessments was found (r = 0.99, P < 0.001). Likewise, the values of the 95% confidence interval (mean +/- 2 SD) for the enzymatic inulin assay showed a good agreement with those achieved with Anthrone (1.14 +/- 0.21 and 1.14 +/- 0.19 mL. min-1. 100 g-1 rat body weight, respectively). CONCLUSIONS: This new approach has methodological and experimental advantages with respect to traditional procedures, making it a useful tool, not only for research purposes but also in the clinical setting.     

Effects of angiotensin II on renal sodium handling and diluting capacity in man pretreated with high-salt diet and enalapril.

The antinatriuretic effect of angiotensin II (Ang II) is generally attributed to a decreased glomerular filtration rate (GFR) and an increased proximal tubular sodium reabsorption. We studied this by infusion of increasing amounts (1, 4, and 8 pmol/kg per min) of Ang II in seven water-loaded volunteers who were pretreated with enalapril and a high-salt diet. While mean arterial pressure increased from 92 +/- 3 mmHg to respectively 98 +/- 3, 110 +/- 2, and 116 +/- 2 mmHg, sodium excretion fell from 331 +/- 40 to 135 +/- 23, 65 +/- 17, and 63 +/- 22 mumol/min, and GFR from 138 +/- 9 to 128 +/- 6, 111 +/- 6, and 104 +/- 8 ml/min (P < 0.05 for each variable). At 1 pmol/kg per min, Ang II decreased maximal urine flow and the fractional excretions of lithium and uric acid. Urine sodium concentration decreased, whereas minimal urine osmolality remained unchanged. At 4 pmol/kg per min, these effects were more pronounced. Moreover, minimal urine osmolality increased from 58 +/- 4 to 72 +/- 8 mosm/kg, but sodium concentration decreased further. The step to 8 pmol/kg per min did not decrease sodium, lithium, or uric acid excretion further, but induced a further increase in minimal urine osmolality to 99 +/- 16 mosm/kg. These data suggest that the antinatriuretic effect of modestly hypertensive dosages of Ang II is not only due to a decrease in GFR and an increase in proximal sodium reabsorption, but also involves a rise in fractional reabsorption in a distal nephron segment. In addition Ang II decreases renal diluting capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced renal reserve and increased cardiac output in adult female sheep uninephrectomized as fetuses

BACKGROUND: Removal of one kidney during the period of nephrogenesis in the sheep leads to offspring with elevated blood pressure and reduced glomerular filtration rate (GFR) at 6 and 12 months of age. The mechanisms underlying the hypertension and the degree of renal impairment are not known. METHODS: Changes in GFR were measured in response to an infusion of amino acids and cardiac output was measured by thermal dilution in female offspring at 2 years of age in eight control (sham-operated) and seven animals that had been unilaterally nephrectomized at 100 days of gestation. RESULTS: Animals uninephrectomized as fetuses had significantly higher blood pressure (91 +/- 2 mm Hg) compared to control animals (86 +/- 2 mm Hg) (P < 0.05). Cardiac output was significantly higher in the uninephrectomized group (148 +/- 10 mL/kg/min) compared to the control group (124 +/- 6 mL/kg/min) (P < 0.05). Heart rate and stroke volume were similar in the two groups although both parameters tended to be higher in the uninephrectomized group. Uninephrectomized animals had a lower basal GFR (P < 0.05). An infusion of amino acids caused a significantly different response in GFR in the two groups (P < 0.01 between the groups) with the uninephrectomized animals having significantly lower GFRs during the infusion period. CONCLUSION: The increased blood pressure observed after fetal uninephrectomy is due to an increase in cardiac output. Thus, formation of a low number of nephrons in utero may predispose an individual to later renal failure and elevated blood pressure.