Atriopeptin does not augment the transvascular flux of macromolecules in the hamster cheek pouch.

Natriuretic peptides elaborated by atrial myocytes promote marked renal sodium and water excretion as a mechanism for fluid and electrolyte balance. Recent evidence suggests that atriopeptin (ANP) also targets the non-renal vasculature as a site for enhanced fluid exchange. It remains unclear whether ANP alters microvascular integrity to facilitate the efflux of both plasma and proteins across the endothelial barrier, or if fluid exchange is selectively enhanced. This study evaluated the influence of ANP on macromolecular transport through the direct observation of microvessels in the hamster cheek pouch using fluorescent intravital microscopy. Fluorescein isothiocyanate conjugated to either bovine serum albumin or dextran 150,000 Mw was utilized as a permeability probe. Macromolecular efflux was quantified as fluorochrome clearance. The clearance of fluorescein-conjugated bovine serum albumin (57.94 +/- 7.03) or fluorescein-conjugated dextran 150 (4.09 +/- 1.35) remained unaltered by intravascular injection of 1 microgram/kg ANP. Topical application of 40 ng to cheek pouch microvessels produced similar results. All pouches demonstrated positive leakage response to histamine 2.5 x 10(-6) M, increasing fluorochrome clearance approximately 2- to 11-fold. Bolus injection of 1 microgram/kg ANP reduced mean arterial pressure, increased urine flow from 6.63 +/- 2.59 microliters/min to 8.20 +/- 6.13 microliters/min, and elevated sodium excretion from 1.37 +/- 0.49 microEq/min to 2.54 +/- 0.99 microEq/min. These results suggest that ANP fails to significantly alter the integrity of the protein-transporting channels in the microvascular exchange barrier.     

Role of increased glomerular filtration rate in atrial natriuretic factor-induced natriuresis in the rat

One of the major renal hemodynamic actions of atrial natriuretic factor (ANF) is to increase glomerular filtration rate (GFR). To assess the role of this effect on ANF-induced natriuresis (UNaV), diuresis (V) and kaliuresis (UKV) we performed late clamp experiments in six rats. After control periods (C), synthetic ANF (auriculin A) was infused i.v. (2 micrograms X min-1/kg body wt) throughout the experiment (150 min). After pre-clamp periods, the perfusion pressure of the left kidney (LK) was reduced to 75-80 mmHg. The right kidney (RK) served as a time control. In LK, before the late clamp, ANF increased (p less than 0.01) GFR from 1.5 +/- 0.1 to 1.8 +/- 0.1 ml/min, V from 17 +/- 5 to 53 +/- 5 microliters/min, and UNaV from 2.1 +/- 0.6 to 10.0 +/- 0.9 microEq/min. Almost identical increases occurred in the RK. The late clamp returned all parameters in LK to C values (p greater than 0.05): GFR to 1.4 +/- 0.1 ml/min, V to 6.3 +/- 1.2 microliter/min, and UNaV to 1.0 +/- 0.3 microEq/min. The late clamp also reversed the ANF-induced increase in UKV. In the RK, GFR (1.8 +/- 0.1 ml/min), V (38 +/- 4 microliter/min) and UNaV (7.8 +/- 0.8 microEq/min) remained elevated (p less than 0.01 vs. C) to the end of the experiment. These data demonstrate that upon return of GFR to control levels, the ANF-induced diuresis, natriuresis and kaliuresis is abolished. The results support our previous view that the increase in GFR together with a decrease in inner-medullary hypertonicity account wholly or in great part for the natriuretic action of ANF.     

The effect of propranolol on renal sodium handling in patients with cirrhosis

Beta-adrenergic blockade by oral propanolol in five cirrhotic patients caused changes in the handling of an acute sodium load. Fractional sodium excretion following an acute saline load increased from 0.69% +/- 0.29 to 1.49% +/- 0.11 (103 microEq/min +/- 7.5 to 129 microEq/min +/- 18) before propranolol administration. After 3 days of oral propanolol 1 mg/kg day, the fractional excretion of sodium by saline loading increased from 0.52% +/- 0.19 to 2.17 +/- 0.19 (109 microEq/min +/- 9 to 178 microEq/min +/- 11). This change was not accompanied by changes in GFR, RPF or in the renin-aldosterone system. The possibility that these changes are caused by a change in the sodium transport at the tubular cell level induced by the beta-adrenergic blockade, is entertained.     

Atrial natriuretic factor in liver cirrhosis--the influence of volume expansion

Plasma levels of atrial natriuretic factor (ANP) were examined in 12 patients with liver cirrhosis (6 with ascites) and 6 controls before and after the administration of the infusion of 2000 ml of saline solution per 70 kg of body weight during 2 hours. Basal concentration of ANF tended to be slightly, but nonsignificantly higher in patients with ascitic liver cirrhosis (5.5 +/- 1.3 fmol/ml) than in controls (3.0 +/- 1.0 fmol/ml) and in patients with non-ascitic liver cirrhosis (4.6 +/- 1.3 fmol/ml). Saline administration led to the comparable increase of plasma ANF in ascitic (14.2 +/- 4.0 fmol/ml) and non-ascitic cirrhotics (15.7 +/- 3.7 fmol/ml) and in controls (12.4 +/- 4.3 fmol/ml). The increase of plasma ANF was accompanied by the suppression of plasma renin activity (PRA) and plasma aldosterone (PA) in all groups; in ascitic patients, however, PRA and PA remained above the normal range. While in controls and non-ascitic cirrhotics saline administration led to the increase of urine flow rate /from 0.74 +/- 0.13 to 2.04 +/- 0.44 ml/min, P less than 0.01, in controls; from 0.83 +/- 0.05 to 1.28 +/- 0.07 ml/min, P less than 0.01, in non-ascitic cirrhotics) and urinary sodium excretion (from 110.7 +/- 21.3 to 364.8 +/- 74.4 umol/min, P less than 0.01, in controls; from 125.0 +/- 16.7 to 218.7 +/- 24.3 umol/min, P less than 0.01 in non-ascitic cirrhotics), in patients with ascitic liver cirrhosis neither urine flow rate (from 0.66 +/- 0.1 to 0.72 +/- 0.15 ml/min, n.s.), nor urinary sodium excretion (from 16.7 +/- 9.9 to 54.2 +/- 40.3 umol/min, n.s.) changed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of clonidine on the kidney function in the anesthetized dog

Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increased urine flow. The response of the kidney has been examined in four combinations. The parameters of renal function have been compared during volume expansion by 1.5-2.0% body weight Ringer solution. In the control animals, volume expansion by 2% body weight, resulted in a slight increase in sodium excretion and urine flow. In 10 anesthetized dogs 1.0 microgram/kg/min of clonidine infused i.v. during 30 minutes (the total amount of clonidine infused was 30 micrograms/kg) decreased the arterial blood pressure from 136 +/- 13 mmHg to 127 +/- 12 mmHg and elevated urine flow from 2.95 +/- 1.65 ml/min to 4.34 +/- 1.77 ml/min while the urine osmolality diminished from 399 +/- 107 mosm/l to 265 +/- 90 mosm/l and the glomerular filtration remained constant. In 5 animals 0.1 microgram/kg/min of clonidine was infused into the left renal artery (this dose is corresponding to the renal fraction of the cardiac output) without any effects in the left kidney. 1.0 microgram/kg/min of clonidine infused directly into the left renal artery produced vasoconstriction in the ipsilateral kidney, decreased the glomerular filtration rate and the urine flow. By contrast in the right kidney the urine flow rose without hemodynamic changes, and the urine osmolality became hypoosmotic compared to the plasma. In ten dogs 1.0 microgram/kg/min of clonidine and 1 mU/kg/min of arginine-vasopressin were infused intravenously. The vasopressin infusion superimposed on the clonidine could not inhibit the increase of the urine excretion, and the fall of the urine osmolality. The results suggest that the clonidine increases the renal medullary blood flow possibly via a direct mechanism, decreases the sympathetic outflow to the kidney and via an indirect pathway, mediated by the renin-angiotensin system. The renal medullary flow increase produces a washout of the medullary osmotic gradient, and the water reabsorption diminishes.     

Zea mays L. extracts modify glomerular function and potassium urinary excretion in conscious rats

Diuretic and uricosuric properties have traditionally been attributed to corn silk, stigma/style of Zea mays L. Although the diuretic effect was confirmed, studies of the plant's effects on renal function or solute excretion were lacking. Thus, we studied the effects of corn silk aqueous extract on the urinary excretion of water, Na+, K+, and uric acid. Glomerular and proximal tubular function and Na+ tubular handling were also studied. Conscious, unrestrained adult male rats were housed in individual metabolic cages (IMC) with continuous urine collection for 5 and 3 h, following two protocols. The effects of 25, 50, 200, 350, and 500 mg/kg body wt. corn silk extract on urine volume plus Na+ and K+ excretions were studied in water-loaded conscious rats (2.5 ml/100 g body wt.) in the IMC for 5 h (Protocol 1). Kaliuresis was observed with doses of 350 (100.42 +/- 22.32-120.28 +/- 19.70 microEq/5 h/100 g body wt.; n = 13) and 500 mg/kg body wt. (94.97+/- 29.30-134.32 +/- 39.98 microEq/5h/100 g body wt.; n = 12; p<0.01), and the latter dose resulted in diuresis as well (1.98 +/- 0.44-2.41 +/- 0.41 ml/5 h/100 g body wt.; n = 12; p<0.05). The effects of a 500 mg/kg body wt. dose of corn silk extract on urine volume, Na+, K+ and uric acid excretions, and glomerular and proximal tubular function, were measured respectively by creatinine (Cler) and Li+ (ClLi) clearances and Na+ tubular handling, in water-loaded rats (5 ml/100 g body wt.) in the IMC for 3 h (Protocol 2). Clcr (294.6 +/- 73.2, n = 12, to 241.7 +/- 48.0 microl/ min/100 g body wt.; n = 13; p<0.05) and the Na+ filtered load (41.9 +/- 10.3, n = 12, to 34.3 +/- .8, n = 13, p<0.05) decreased and ClLi and Na+ excretion were unchanged, while K+ excretion (0.1044 +/- 0.0458, n=12, to 0.2289 +/- 0.0583 microEq/min/100 body wt.; n = 13; p<0.001) increased. For Na+ tubular handling, the fractional proximal tubular reabsorption (91.5 +/- 3.5, n = 12, to 87.5 +/- 3.4%; n = 13; p<0.01) decreased, and both fractional distal reabsorptions--I and II--increased (96.5 +/- 1.5, n = 12, to 97.8 +/- 0.9%; n = 13; p<0.01; and 8.2 +/- 3.5, n = 12, to 12.2 +/- 3.4%, n = 13, p<0.01, respectively). To summarize, in water-loaded conscious rats (2.5 ml/100 body wt.), corn silk aqueous extract is diuretic at a dose of 500 mg/kg body wt. and kaliuretic at doses of 350 and 500 mg/kg body wt. In water-loaded conscious rats (5.0 ml/100 g body wt.), corn silk aqueous extract is kaliuretic at a dose of 500 mg/kg body wt., but glomerular filtration and filtered load decrease without affecting proximal tubular function, Na+, or uric acid excretion.     

Volume expansion during NOS substrate donation with L-arginine: regulatory offsetting of renal response?

The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg.kg(-1).min(-1)) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 +/- 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 +/- 0.0 to 0.7 +/- 0.1 ml/min). Volume expansion increased arterial blood pressure (102 +/- 3 to 114 +/- 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 +/- 31 micromol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 +/- 1.7 to 1.6 +/- 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 +/- 23 micromol/min at plasma ANG II levels of 3.0 +/- 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.     

Vascular reactivity to norepinephrine in rats with cirrhosis of the liver

Vascular reactivity to norepinephrine was studied in rats with early cirrhosis of the liver and in control rats. Cirrhotic rats showed water and sodium retention but not ascites. Studies were performed in whole animals, isolated hindquarters, and isolated femoral arteries. Plasma catecholamine levels were measured by radioenzymoassay and their urinary metabolites by gas-liquid chromatography. Plasma norepinephrine was 331 +/- 49 pg/mL (mean +/- SEM) in control rats and 371 +/- 66 pg/mL in cirrhotic animals (p greater than 0.05). No differences in plasma epinephrine or dopamine were observed. Urinary excretion of catecholamine metabolites was increased in cirrhotic rats. These data suggest a moderate activation of the sympathetic nervous system. In basal conditions, cirrhotic rats showed lower mean arterial pressure than controls (101 +/- 4 vs. 116 +/- 4 mmHg (1 mmHg = 133.3 Pa); p less than 0.01). However, perfused hindlimb resistance was similar in cirrhotic and in control animals. In the whole animal and in the perfused hindquarter, the contractile response to norepinephrine was similar for control and for cirrhotic rats. The contractile response to norepinephrine exhibited by isolated femoral arteries was similar in those from cirrhotic and control rats. This indicates that the peripheral vascular bed has a well-maintained ability to constrict in response to norepinephrine, suggesting that circulatory abnormalities in early experimental cirrhosis are not caused by refractoriness of the vascular smooth muscle to norepinephrine.     

Natriuretic effect of atrial natriuretic peptide in diabetes insipidus rats

Washout of the solute concentration gradient in the renal medullary interstitium has been suggested to play a role in mediating the natriuretic response to atrial natriuretic peptide (ANP). The purpose of this study was to determine the effects of ANP 8-33 on sodium excretion in Brattleboro diabetes insipidus (DI) rats, in which medullary tonicity is known to be decreased as compared to Long-Evans (LE) control rats. Basal urine osmolality (Uosm) was significantly lower in DI rats as compared to LE rats (123 +/- 6 vs 673 +/- 38 mOsm/kg). Infusion of ANP 8-33 at a rate of 4 micrograms/kg/hr for 60 min resulted in a significantly greater increase in UnaV (delta 6.1 +/- 1.2 vs delta 2.9 +/- 0.7 microEq/min) and urine flow (delta 40 +/- 12 vs delta 8 +/- 7 microliter/min) in the LE rats than in the DI rats. The greater natriuresis occurred in the LE rats despite no significant change in Uosm. Fractional lithium reabsorption (an indicator of proximal sodium reabsorption) decreased similarly in both groups. Infusion of ANP had no effect on mean arterial pressure in LE and DI groups. In summary, infusion of ANP in the DI rat resulted in a significant natriuresis, albeit less than in LE rats. The natriuresis in the LE rats occurred despite no significant change in Uosm. These data suggest that mechanisms other than medullary washout are responsible for the natriuretic effects of ANP.     

Renal effects of dopamine and ANP in high volume expanded rats

Both dopamine (DA) and atrial natriuretic peptide (ANP) have been postulated to exert similar effects on the kidney, participating in the regulation of body fluid and sodium homeostasis. In the present study, experiments were performed in anesthetized and isotonic sodium chloride volume expanded rats. After acute volume expansion at 15 % of body weight during 30 min, glomerular filtration rate, urine output, sodium excretion, fractional sodium excretion, proximal and distal sodium excretion and blood pressure were measured. In additional groups we administered ANP or haloperidol or the combination of both to volume expanded animals. Blockade of DA receptors with haloperidol, attenuated diuretic and natriuretic responses to volume load. Proximal sodium excretion was not modified by haloperidol in all experimental groups of rats. Reduction in distal tubular excretion was induced by haloperidol in saline infusion expanded rat but not in ANP treated expanded animals. In conclusion, when exaggerated volume expansion is provoked, both DA and ANP exert renal tubular events, but ANP have a major central role in the regulation of renal sodium handling.     

Glomerular filtration rate and blood pressure monitoring in awake baboons

Minimally invasive techniques were used to collect urine with an external catheter together with automated intermittent monitoring of arterial blood pressure in awake male baboons. Using endogenous creatinine, 24-hour creatinine clearances were measured for 2 to 3 consecutive days in four intact and in four uninephrectomized baboons. Despite large differences in urinary volume and sodium excretion, reproducibility of 24-hour creatinine clearances was within 15% in 15 of 19 studies obtained from 6 of 8 animals. Arterial blood pressure was monitored intermittently at 30 to 60 minute intervals over 24 hours with a Dinamap monitor and recorder. Mean blood pressure averaged 71 +/- 4.4 to 89 +/- 5.5 mm Hg in different animals. Blood pressure tended to be lower at night than during the day. In separate studies using 15 to 60 minute urine collection periods, inulin clearance was compared in awake and in anesthetized animals with endogenous or exogenous creatinine clearance measured simultaneously. The clearance of creatinine systematically exceeded the clearance of inulin, even in intact animals with a normal serum creatinine. The creatinine-to-inulin clearance ratio averaged 1.16 +/- 0.03 at a serum concentration of 0.7 to 0.8 mg/dl; 1.27 +/- 0.03 at a serum creatinine of 1.0 to 1.1 mg/dl and 1.56 +/- 0.04 at a serum creatinine greater than 10 mg/dl. All values exceed unity significantly (p less than 0.001). Thus, renal function, including inulin clearance, can be measured in awake baboons. Duplicate or triplicate 24-hour urine collections are needed to assess the reliability of creatinine excretion. However, creatinine clearance overestimates glomerular filtration rate, as it does in humans.     

Haemodynamic effects of angiotensin II in conscious, non-ascitic cirrhotic rats

The effect of angiotensin II (AII) on systemic and regional haemodynamics was studied in 18 control and 18 cirrhotic, non-ascitic conscious rats (CCl4/phenobarbital model). Cirrhotic rats were found to retain sodium and to have normal plasma renin and plasma aldosterone concentrations when compared with control animals. Cirrhotic rats showed an enhanced cardiac output (34.4 +/- 0.5 vs. 27.5 +/- 2.0 ml/min in controls) and decreased peripheral resistances (2.96 +/- 0.25 vs. 3.95 +/- 0.31 mm Hg/min/100 g/ml in controls) under basal conditions. When AII was administered cardiac output decreased by 10.7 +/- 1.2% in cirrhotic rats, whereas it increased in control animals (11.2 +/- 2%, p less than 0.005). The AII-induced increase in arterial pressure was lower in cirrhotic than in control rats. The renal blood supply was particularly impaired by AII in cirrhotics, with a maintained flow to other organs (muscle, testes). It is concluded that the response to AII is disturbed in rats with hepatic cirrhosis even in a stage without ascites and with plasma renin and aldosterone concentrations similar to those of control animals.     

Effect of ventilation on sodium excretion in the anesthetized dog with unilateral renal denervation

We studied if the effect of mechanical ventilation induced to keep arterial blood gas values within normal physiological limits has any influence on renal sodium excretion in anesthetized dogs (n = 17) subjected to acute unilateral renal denervation. Compared to the control and the postcontrol periods, ventilation elevated arterial pO2 from 86 +/- 5 to 96 +/- 5 mmHg and blood pH from 7.37 +/- 0.02 to 7.41 +/- 0.01 while arterial pCO2 was decreased from 38 +/- 2 to 33 +/- 1 mmHg (p less than 0.05 in all cases). Compared to the innervated kidney urine flow, urinary sodium and potassium excretion from the denervated kidney were markedly elevated both during spontaneous respiration and during mechanical ventilation but GFR and cPAH were similar on the two sides. Ventilation decreased sodium excretion by the denervated kidney from 314 +/- 26 to 252 +/- 31 mumols/min/100 g k. w. (p less than 0.05). No other excretory changes were noted either in the innervated or in the denervated kidneys. Difference in sodium excretion between innervated and denervated kidneys was decreased from 209 +/- 19 to 126 +/- 20 mumole/min/100 g k. w. (p less than 0.001), due to the ventilation induced diminution of sodium excretion from the denervated kidney. It is concluded that mechanical ventilation of anesthetized dogs modifies sodium excretion, and this phenomenon can be demonstrated only in the denervated kidney.     

Reduced natriuresis after oral sodium load in cholestatic rats: role of compartment volumes and ANP

The purpose of this study was to assess the participation of the atrial natriuretic peptide (ANP)-cGMP system in electrolyte and volume handling of cholestatic rats submitted to an acute oral sodium load. Cholestasis was induced by ligation and section of the common bile duct (n = 51). Control rats were sham operated (n = 56). Three weeks after surgery, 24-hr urinary volume, sodium, potassium, cGMP and creatinine excretion were measured. Three days later, animals received 10 mmol/kg NaCl (1 M) by gavage, and urinary excretion was measured for 6 hr. In parallel groups of rats, plasma volume, electrolytes and ANP concentration, extracellular fluid volume (ECFV), and renal medullary ANP-induced cGMP production were determined in basal conditions or 1 hr after oral sodium overload. As compared with controls, cholestatic rats had a larger ECFV and higher plasma ANP (67.2 +/- 5.2 vs 39.7 +/- 3.5 pg/ml), but lower hematocrit and blood volume, and were hyponatremic. Cholestatic rats showed higher basal excretion of sodium, potassium, and volume than controls, but equal urinary cGMP. After the NaCl overload, cholestatic rats showed a reduced sodium excretion but equal urinary cGMP. One hr after sodium overload, both groups showed hypernatremia, but whereas in control rats ECFV and ANP increased (50.7 +/- 4.1 pg/ml), in cholestatic rats ECFV was unchanged, and plasma volume and ANP were reduced (37.5 +/- 5.8 pg/ml). ANP-induced cGMP production in renal medulla was similar in cholestatic and control nonloaded rats (14.2 +/- 5.2 vs 13.4 +/- 2.6 fmol/min/mg). One hr after the load, medullary cGMP production rose significantly in both groups, without difference between them (20.6 +/- 3.1 vs 22.7 +/- 1. 7 fmol/min/mg). We conclude that the blunted excretion of an acute oral sodium load in cholestatic rats is associated with lower plasma ANP due to differences in body fluid distribution and cannot be explained by renal refractoriness to ANP.     

Head-down tilt and restraint on renal function and glomerular dynamics in the rat

A model utilizing 25 degree head-down tilt (HDT) and incorporated with chronic catheterization and renal micropuncture techniques in rats was employed to study alterations in renal function induced by HDT. Renal function and extracellular volume measurements were performed after 24 h, 4 days, and 7 days of HDT in conscious rats and compared with their own control measurements and to nontilted but similarly restrained rats. After 24 h HDT, glomerular filtration rate (GFR) increased 19 +/- 8% and renal plasma flow (RPF) increased 18 +/- 8% with increases in urine flow rate, Na+, and K+ excretion in conscious rats. These increases after 24 h were associated with an increase in extracellular volume of 16 +/- 3% (P less than 0.01). In the nontilted controls, there was a decrease in extracellular volume after 24 h of suspension. After 7 days of HDT, GFR was decreased by 7 +/- 1% (P less than 0.01), but RPF and extracellular fluid volume were not different from control values. However, RPF and GFR increased in the nontilted rats after 7 days. After 7 days of HDT renal micropuncture studies demonstrated that single-nephron filtration rate was also decreased from 43 +/- 2 to 31 +/- 3 nl/min (P less than 0.05) due solely to reductions in the glomerular ultrafiltration coefficient (0.11 +/- 0.01 to 0.07 +/- 0.01 nl.s-1 X mmHg-1, P less than 0.05). There was a dissociation between GFR and water and Na+ excretion at days 4 and 7 of HDT not observed in the nontilt restraint controls.     

Cardiovascular and renal characteristics, and responses to acute volume expansion of a rat model of diabetic pregnancy

The objective of this study was to characterize the cardiovascular and renal alterations that occur during diabetic pregnancy, and to evaluate the effect of insulin treatment in 12-14 days pregnant diabetic rats. Four groups of female Sprague Dawley rats were studied: virgin control group (NP), pregnant control group (CP), diabetic pregnant group (DP), and diabetic pregnant group with insulin treatment (DPI). Systolic arterial pressure (SAP) was increased on day 12, whereas heart rate (HR) decreased starting with day 3 in DP group of rats. DP rats exhibited marked renal hypertrophy with greater kidney weight (wt) and kidney wt/body wt ratio. Insulin treatment normalized blood glucose (BG) concentration, SAP and HR, and prevented the increase in kidney wt/body wt ratio in DPI rats. At the time of the terminal acute experiment, acute saline volume expansion (VE, 5% body wt/30 min) significantly increased renal interstitial hydrostatic pressure (RIHP), urinary sodium excretion (U(Na)V) and urine flow rate (V) in all groups, but the increases (Delta) were significantly attenuated in both CP (1.7 +/- 0.2mmHg, 12.0 +/- 1.5 microEq.min(-1).g kidney wt(-1) and 76.2 +/- 10.9 microl.min(-1).g kidney wt(-1) for DeltaRIHP, DeltaU(Na)V and DeltaV respectively) and DP (1.3 +/- 0.1 mmHg, 6.8 +/- 1.8 microEq.min(-1).g kidney wt(-1) and 32.3 +/- 9.3 microl.min(-1).g kidney wt(-1) for DeltaRIHP, DeltaU(Na)V and DeltaV respectively) group of rats as compared to NP (4.0 +/- 0.6 mmHg, 21.6 +/- 1.4 microEq.min(-1).g kidney wt(-1)and 136.8 +/- 10.5 microl.min(-1).g kidney wt(-1) for DeltaRIHP, DeltaU(Na)V and DeltaV respectively) group of rats. Although RIHP response to VE was similar in DP and CP group of rats, the natriuretic and diuretic responses to VE were significantly lower in DP as compared to CP group of rats. Insulin treatment had no effect on RIHP response (DeltaRIHP = 1.5 +/- 0.3 mmHg), but restored most of the natriuretic (DeltaU(Na)V = 15.7 +/- 2.9 microEq.min(-1).g kidney wt(-1)) and diuretic (DeltaV = 100.2 +/- 19.3 microl.min(-1).g kidney wt(-1)) responses to VE in DPI as compared with CP group of rats. These data suggest that with VE, the restoration of the increase in U(Na)V and V with insulin treatment in diabetic pregnant rats is not mediated by changes in RIHP.     

Effects of atrial appendectomy on circulating atrial natriuretic factor during volume expansion in the rat

This study examined the changes in the circulating level of endogenous atrial natriuretic factor during diuresis and natriuresis produced by acute volume expansion in anesthetized rats with either bilateral atrial appendectomy (n = 9) or sham operation (n = 9). Following control measurements in the sham-operated rats, 1% body weight volume expansion with isotonic saline produced an increment in urinary sodium excretion of over 4 mueq/min (P less than 0.05) while urine volume increased by more than 20 microliter/min (P less than 0.05). These responses were associated with a significant increase in immunoreactive plasma atrial natriuretic factor from a baseline value of 82 +/- 10 pg/ml to a level of 120 +/- 14 pg/ml (P less than 0.05). In contrast, in the group of rats with bilateral atrial appendectomy an identical degree of volume expansion increased urinary sodium excretion and urine volume by only 0.61 mueq/min (P less than 0.05) and 3.07 microliter/min (P less than 0.05), respectively. In this group, immunoreactive plasma atrial natriuretic factor remained statistically unchanged from a control value of 70 +/- 12 pg/ml to a level of 82 +/- 16 pg/ml (P greater than 0.05). Comparison of the two groups indicates that the natriuresis, diuresis, and plasma atrial natriuretic factor levels during volume expansion were significantly reduced in the rats with bilateral atrial appendectomy. No differences in mean arterial pressure and heart rate were observed between the two groups. These data demonstrate that removal of both atrial appendages in the rat attenuated the release of atrial natriuretic factor during volume expansion; and this effect, in turn, was associated with a reduction in the natriuretic and diuretic responses.     

Renal function studies in an experimental model of papillary necrosis in the rat

Twenty four hours after i.v. injection of bromoethylamine-hydrobromide (BEA) in rats, a uniform papillary necrosis is observed. The present study investigates the renal functional and the papillary haemodynamics in response to acute volume expansion (12% of body weight) in this model. Renal function studies were performed in hydropenic and volume expanded sham- or BEA-injected rats. In hydropenic normal animals a GFR of 1.97 +/- 0.14 ml/min, an urinary osmolarity (UOsm) of 1 011 +/- 94.5 mOsm/kg and a fractional sodium excretion (FENa) of 0.18 +/- 0.026% were obtained. In contrast, BEA-treated hydropenic animals showed a lower GFR (1.16 +/- 0.14 ml/min), UOsm (469 +/- 30.31 mOsm/kg) and a higher FENa (0.37 +/- 0.06%). In volume expansion a similar UOsm and FENa were obtained in both groups. The papillary plasma flow (PPF) was measured in each of the experimental groups by the albumin accumulation technique. The mean value in hydropenic normal animals was 50.65 +/- 2.12 m 100 g-1 min-1 and increased to 66.02 +/- 2.00 ml 100 g-1 min-1 after volume expansion (P less than 0.001). In BEA rats the PPF was 58.86 +/- 2.33 ml 100 g-1 min-1 in hydropenia (P less than 0.01 vs. control animals) and remained unchanged after volume expansion. Thus, during hydropenia, BEA-induced papillary necrosis results with a salt wasting state and an urinary concentration defect. After volume expansion no disturbance in sodium excretion capacity was observed. These results are compatible with the nephron-heterogeneity concept in the regulation of sodium excretion. The histological lesions cannot be explained by a decreased renal papillary plasma flow.     

脑室内注射高张盐水抑制近曲小管对水和钠的重吸收

实验在麻醉大鼠上进行。用锂清除率为指标观察脑室内注射高张盐水对近曲小管重吸收水和钠的影响。在切断单侧肾神经的动物中,脑室内注射高张盐水后的锂清除率与肾小球滤过率比值在去神经侧肾脏从0.37±0.04增加至0.51±0.05(P<0.01);神经完好侧肾脏则从0.26±0.03增加至0.31±0.04(P<0.05);双侧肾脏的肾小球滤过率、尿量、尿钠和尿钾量均增加,且去肾神经肾脏的增加幅度高于肾神经完好肾脏。在肾小管微穿刺实验中,脑室内注射高张盐水后,近曲小管末段小管液流量从24.42±1.84nl/min增加至31.86±3.09nl/min(P<0.01),小管液的渗透压无显著变化。以上实验结果表明,脑室内注射高张盐水引起的利尿、尿钠增多反应与肾小球滤过率增加和近曲小管对水、钠重吸收减少有关,体液因素在该反应中可能起主要作用。     

Effects of atrial natriuretic factor on urinary concentration of catecholamines and renin secretion in dogs

This study evaluated the effects of synthetic atrial natriuretic factor (ANF) on renal hemodynamics, urinary excretion of electrolytes, norepinephrine (NE), and dopamine (DA); and renal production of renin in anesthetized dogs. Following a bolus (1 micrograms/kg body weight) and infusion (0.1 microgram/kg/min) for 30 min, there was significant increase in urine flow (220 +/- 41%), glomerular filtration rate (72 +/- 14%), and urinary sodium excretion (170 +/- 34%). There was a decrease in renin secretory rate and the concentration ratio of urine NE to DA following ANF was decreased (p less than 0.05). These data suggest that ANF decreases renal production of NE and renin.