Role of neuronal nitric oxide synthase in mediating renal hemodynamic changes during pregnancy

Renal plasma flow (RPF) and glomerular filtration rate (GFR) are markedly increased during pregnancy. We recently reported that the renal hemodynamic changes observed during pregnancy in rats are associated with enhanced renal protein expression of neuronal nitric oxide synthase (nNOS). The purpose of this study was to determine the role of nNOS in mediating renal hemodynamic changes observed during pregnancy. To achieve this goal, we examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) on kidney function in normal conscious, chronically instrumented virgin (n = 6) and pregnant rats (n = 9) at day 16 of gestation. Infusion of 7-NI had no effect on RPF (4.7 +/- 0.7 vs. 4.8 +/- 0.9 ml/min), GFR (2.2 +/- 0.2 vs. 2.5 +/- 0.4 ml/min), or mean arterial pressure (MAP; 127 +/- 7 vs. 129 +/- 10 mmHg) in virgin rats. In contrast, 7-NI infused into pregnant rats decreased RPF (8.9 +/- 1.6 vs. 6.5 +/- 1.4 ml/min) and GFR (4.4 +/- 0.7 vs. 3.3 +/- 0.7 ml/min) while having no effect on MAP (123 +/- 4 vs. 123 +/- 3 mmHg). In summary, inhibition of nNOS in pregnant rats at midgestation results in significant decreases in RPF and GFR. nNOS inhibition in virgin rats had no effect on renal hemodynamics. These data suggest that nNOS may play a role in mediating the renal hemodynamic changes that occur during pregnancy.     

The effects of atrial natriuretic peptide on whole-kidney and proximal straight tubular function in the rabbit

The mechanisms by which atrial natriuretic peptide (ANP) produces a diuresis and natriuresis remain unclear. It has been suggested that the major if not sole mediator of ANP's renal effects is a hemodynamically induced increase in glomerular filtration rate (GFR). Data from clearance studies in anesthetized rabbits demonstrate that ANP administration can produce a significant increase in absolute and percentage sodium excretion (42.0 +/- 5.9----64.6 +/- 10.2 mu eq/min, P less than 0.01, and 1.97 +/- 0.28----3.12 +/- 0.35%, P less than 0.001, respectively) without increasing GFR (16.8 +/- 2.1----16.1 +/- 2.5 cc/min, P greater than 0.30). The natriuresis occurred despite a fall in renal plasma flow (RPF) (56.7 +/- 7.0----44.5 +/- 9.4 cc/min, P less than 0.01), a rise in filtration fraction (0.33 +/- 0.01----0.46 +/- 0.05, P less than 0.01), and an unchanged filtered load of sodium (2.28 +/- 0.27----2.16 +/- 0.32 mu eq/min, P greater than 0.10). Isolated tubular microperfusion studies demonstrated that ANP, present as a 10(-9) M concentration in the solution bathing perfused proximal straight tubules (PST), did not affect fluid flux (Jv) (0.38 +/- 0.07----0.41 +/- 0.07 nl/mm/min, P greater than 0.30) or phosphate reabsorption (Jp) (1.50 +/- 0.5----1.38 +/- 0.36 pmole/mm/min, P greater than 0.50). When ANP was infused into rabbits prior to harvesting the PSTs for isolated tubular microperfusion and the results were compared to tubules taken from control animals, there was again no effect on Jv (0.37 +/- 0.05 vs 0.42 +/- 0.05 nl/mm/min, P greater than 0.50) or Jp (2.41 +/- 0.27 vs 2.42 +/- 0.44 pmole/mm/min, P greater than 0.90). These findings suggest that ANP can inhibit sodium transport without increasing whole-kidney GFR or RPF, but does not directly inhibit transport in the proximal straight tubule.     

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。     

Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation

Our previous data indicated that various subtypes of connexin (Cx) were expressed in the juxtaglomerular apparatus. Experiments were performed to characterize the effects on renal autoregulation of specific mimetic peptides that inhibit these Cx subtypes in Wistar-Kyoto rats. Intrarenal infusion of (Cx37,43)GAP27 increased autoregulatory index of renal plasma flow (0.06 +/- 0.05 to 0.47 +/- 0.06, n = 6, P < 0.05) and glomerular filtration rate (GFR; 0.01 +/- 0.07 to 0.49 +/- 0.07, P < 0.05). The additional administration of 8-cyclopentyl- 1,3-dipropylxanthine (CPX) produced a further elevation of autoregulatory index of RPF (0.86 +/- 0.07, P < 0.05) and GFR (0.88 +/- 0.09, P < 0.05), compared with (Cx37,43)GAP27 alone. However, the addition of pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS) to (Cx37,43)GAP27 did not. Combined treatment with CPX and PPADS markedly worsened autoregulatory index of RPF (0.04 +/- 0.10 to 0.81 +/- 0.06, n = 6 P < 0.01) and GFR (0.05 +/- 0.08 to 0.79 +/- 0.05, P < 0.01). (Cx40)GAP27 induced similar changes to (Cx37,43)GAP27. Renal autoregulation was preserved in the presence of (Cx43)GAP26. Our results indicate that the inhibition of gap junction impaired renal autoregulation. Furthermore, the present data provide evidence that both adenosine and purinergic receptors contribute to glomerular autoregulation. Finally, our findings suggest that gap junctions, at least in part, transduce purinergic signals mediating renal autoregulation.     

Relationship Between Orcadian Changes in Renal Hemodynamics and Circadian Changes in Urinary Glycosaminoglycan Excretion in Normal Rats

Circadian changes in renal hemodynamics and urinary glycosaminogly-can (GAG) excretion were studied in normal Sprague-Dawley rats to further investigate rhythms in kidney function. Urinary water, protein, and GAG excretion, as well as glomerular filtration rate (GFR) and renal plasma flow (RPF), were determined every 4h over the 24h cycle in an attempt to characterize any temporal changes. Urinary flow rate and proteinuria peaked during the dark activity period of the animals, consistently at the same hour, whereas the lowest values were detected during the resting phase. GAG are mucopolysaccharides entering the constitution of the glomerular basement membrane (GBM), which is the key component in the process of glomerular filtration. Similarly, the urinary excretion rate of GAG showed a circadian rhythmicity in phase with urinary water and protein excretion, with markedly increased values observed during the nocturnal phase of the animals. Moreover, GFR and RPF were demonstrated to exhibit large circadian variations in phase with renal excretory rhythmicity, showing nighttime values significantly greater compared to daytime ones. Strong correlations were found between GFR and RPF rhythms, as well as between GAG and GFR, and GAG and RPF rhythms, although the latter were not statistically significant. This pattern suggests that the circadian rhythmicity in urinary excretion rate of GAG in physiological conditions could presumably be secondary to the temporal changes in renal hemodynamics. In this respect, knowledge of renal chronobiology helpfully contributes to increase our understanding of renal physiology.     

大鼠脑胆碱能系统对血量扩张引起利尿与尿钠排泄...

The role of brain cholinergic system on diuresis and natriuresis induced by volume expansion was studied in conscious rats. In a series of experiments, the diuretic, natriuretic and kaliuretic responses induced by volume expansion were compared in three groups of conscious rats pretreated respectively with intracerebroventricular (icv) injection of artificial cerebrospinal fluid (ACSF), atropine and hexamethonium. The natriuretic, kaliuretic and diuretic responses induced by volume expansion were much less in the animals with icv injection of atropine than in the control group with injection of ACSF (P less than 0.01). While the group pretreated with icv injection of hexamethonium showed no significant decrease in these responses of volume expansion than that of the control (P greater than 0.05). Volume expansion produced no change in insulin and PAH clearance in both the atropine and the ACSF group. Thus the atropine suppressed diuresis, natriuresis and kaliuresis are independent of changes in GFR and RPF. It is inferred from the results of the present investigation that volume expansion induced diuresis and natriuresis appear to be due to inhibition of water and sodium reabsorption in the renal tubules and regulated by certain brain cholinergic system.     

The action of lipoxin-A on glomerular microcirculatory dynamics in the rat

Intrarenal administration of 750 ng/kg/min of LX-A in euvolemic rats resulted in significant increases in single nephron GFR (38.4 +/- 1.7 to 45.5 +/- 3.0 nl/min) and plasma flow rate (95 +/- 6 to 127 +/- 9 nl/min). The latter was due to a dramatic fall in afferent arteriolar resistance. Mean transcapillary hydraulic pressure difference increased from 33 +/- 1 to 43 +/- 3 mmHg (p less than 0.05) and the glomerular capillary ultrafiltration coefficient fell from 0.060 +/- 0.013 to 0.033 +/- 0.005 nl/(s X mmHg) (p less than 0.05). These responses to LXA in the renal microcirculation are in sharp contrast to those previously observed for the leukotrienes, and thus may represent the first example of counterregulatory (constrictor/dilator) vascular interactions within the lipoxygenase pathways.     

Responsiveness of renal glomeruli to adenosine in streptozotocin-induced diabetic rats dependent on hyperglycaemia level.

Glomerular filtration rate (GFR) in response to adenosine precursor, NAD, and glomeruli contractility in response to adenosine were evaluated in streptozotocin-induced diabetic rats with severe (blood glucose 27.8 +/- 1.2 mmol/L) and moderate hyperglycaemia (18.2 +/- 0.9 mmol/L) compared with nondiabetic (ND)-rats. In anaesthetised rats, basal GFR was greater in moderately diabetic rats compared with severely diabetic rats (p < 0.05) and ND-rats (p < 0.02). Intravenous infusion of 5 nmol x min(-1) x kg(-1) NAD reduced GFR and renal plasma flow (RPF) in diabetic rats but had no effect on these parameters in ND-rats. Moreover, NAD-induced reduction of GFR and RPF was greater in rats with severe diabetes (41% and 30%, respectively) than in with moderate diabetes (25% and 26%, respectively). Theophylline (0.2 micromol x min(-1) x kg(-1) ) abolished renal response to NAD. Isolated glomeruli contraction in response to adenosine, assessed by glomerular 3H-inulin space reduction, was lowered in moderately diabetic-group and enhanced in severely diabetic-group. compared with ND-group (p < 0.05). Adenosine A1-receptor antagonist DPCPX inhibited adenosine-induced glomeruli contraction. This differential response of diabetic renal glomeruli to adenosine suggests that impaired glomerular contractility in response to adenosine could be responsible for hyperfiltration in moderate diabets, whereas, the increased adenosine-dependent contractility of glomeruli in severe diabetes may increase the risk of acute renal failure in this condition.     

Alterations in glomerular and tubular dynamics at 1 and 14 days simulated microgravity and after acute return to orthostasis

Head-down tilt (HDT) is utilized to simulate microgravity and produces a cephalad fluid shift, which results in alterations in fluid and electrolyte balance. These changes in volume homeostasis are due, in part, to alterations in multiple volume control mechanisms in which renal function is a major participant. We have previously demonstrated that glomerular filtration rate increases early in HDT and eventually returns to values not different from non-tilt measurements. This early increase in glomerular filtration rate was also demonstrated during days 2 and 8 of the SLS-1 mission. However, urine flow and electrolyte excretion does not parallel the alterations in glomerular filtration rate and the site of this change in nephron fluid reabsorption pattern has not been previously examined. Through determination of the location of alterations in tubular fluid reabsorption within the nephron, a more detailed hypothesis can be forwarded as to which specific neuro-humoral agents participating in control of renal function in microgravity conditions. The importance of this type of examination is that measurements in circulating neuro-humoral agents and urinary excretion patterns alone are not accurate predictors of how renal functional response may alter to head-down tilt or other models of simulated weightlessness. To examine this issue, renal micropuncture techniques were utilized in Munich-Wistar rats submitted 24 hours and 14 day head-down tilt, measuring all the determinants of glomerular ultrafiltration and obtaining data regarding segmental tubular fluid reabsorption. Following these measurements, the rats were returned to an orthostatic position and after 60 min, the measurements were repeated.     

Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat.

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1--2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4--5 days before UUO denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney. It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.     

Effect of unilateral nephrectomy on renal function of diabetic rats

Glomerular alterations of experimental diabetes mellitus are observed in animals submitted to a reduction in renal mass, suggesting that some mechanisms responsible for the progression of renal disease are common. The aim of this study was to investigate the effect of nephrectomy on the renal function and morphology of diabetic rats. Male Wistar rats were divided into 4 groups: control (C), n=8; diabetic (DM), n=8; non-diabetic nephrectomized (Nx), n=8; (DMNx), n=9. DM was induced by streptozotocin (65 mg/Kg), and animals were treated with insulin. After 12 weeks, the glomerular filtration rate (GFR), renal plasma flow (RPF) and mean arterial pressure (MAP) were evaluated in unanaesthetized animals. Glomerular volume (GV), glomerular sclerosis index (GSI), mesangial volume density (Vvmes) and glomerular capillary surface density (Svcap) were also evaluated. Results show that kidney weight increased in Nx groups, being higher in DMNx. GFR was higher in Nx groups as was RPF, being higher in DMNx. RVR was lower in Nx groups, especially in DMNx. MAP was not different among the groups. RPF and GFR showed a high correlation for the DMNx group (r=0.95, p=0.02). The DMNx group showed a correlation between RVR and GFR (r=-0.96, p=0.005). The GV increased in Nx groups, and the GSI was higher in DMNx. Vvmes and Svcap increased in DMNx group. In summary, Nx groups developed similar degrees of glomerular hypertrophy, but only DMNx showed an increased value for GSI. The present data suggest that the acceleration of glomerular lesions in DMNx animals was more closely associated to hemodynamic adaptations than to glomerular hypertrophy.     

Mechanisms of the early and late response of the kidney to contralateral nephrectomy.

The immediate (1 day, D1) and late (90 days, D90) effects of unilateral nephrectomy on contralateral renal hemodynamics, and the renal handling of electrolytes and water were investigated in the whole animal. The immediate and late ability of the remnant kidney to autoregulate perfusate flow and glomerular filtration rate (GFR) was studied in the isolated perfused kidney of the rat. In the whole animal, in D1 rats as compared to controls, GFR calculated for a single kidney increased from 0.85 +/- 0.3 to 1.1 +/- 0.2 ml/min (p less than 0.05). In D90 rats GFR increased further and was similar to prenephrectomy GFR (1.4 +/- 0.5 vs. 1.7 +/- 0.5 ml/min, p NS). Urinary prostanoid excretion in 24 h, calculated for one kidney, increased by 50-500% in D1 rats, but returned to prenephrectomy values in D90 rats. In the isolated perfused kidney, decreasing perfusion pressure (PP) from 100 to 70 mmHg did not change the renal vascular resistance (RVR) in control and D90 kidneys, but in D1 kidneys RVR decreased from 8.6 +/- 1.3 to 7 +/- 1.3 mm Hg/ml/min (p less than 0.05). In D90 kidneys RVR was significantly lower as compared to control and D1 kidneys at all perfusion pressures. Decreasing PP from 100 to 70 mm Hg resulted in a significant decrease in perfusion flow in control, D1 and D90 kidneys, while with the increase in PP from 100 to 130 mm Hg the perfusion flow increased significantly in all three kidney groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the prostacyclin analogue iloprost in sodium-depleted rats pretreated with captopril.

Previous studies have shown that administration of captopril to sodium-depleted rats decreases the glomerular filtration rate (GFR) and blunts the increase in glomerular prostacyclin synthesis normally occurring in response to sodium depletion. To clarify the relationship between these two responses, iloprost, a stable analogue of prostacyclin, was administered to Na-depleted, captopril-treated (LNC) rats. At a dosage not affecting systemic blood pressure (12.5 ng/kg/min), iloprost increased GFR in LNC rats by 25% (from 0.26 +/- 0.03 to 0.35 +/- 0.03 ml/min/100 g body wt, P less than 0.01), without significant effects on renal plasma flow. No effect was observed in control rats. The results suggest that altered prostacyclin synthesis could contribute to the decrease of GFR in this model.     

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

Increased intra-abdominal pressure (IAP) during laparoscopy adversely affects kidney function. The mechanism underlying this phenomenon is largely unknown. This study was designed to investigate the involvement of endothelin (ET)-1 and nitric oxide (NO) systems in IAP-induced renal dysfunction. Rats were subjected to IAP of 14 mmHg for 1 h, followed by a deflation for 60 min (recovery). Four additional groups were pretreated with 1) ABT-627, an ET(A) antagonist; 2) A-192621, an ET(B) antagonist; 3) nitroglycerine; and 4) N(G)-nitro-L-arginine methyl ester, a NO synthase inhibitor, before IAP. Urine flow rate (V), absolute Na+ excretion (U(Na)V), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. Significant reductions in kidney function and hemodynamics were observed when IAP was applied. V decreased from 8.1 +/- 1.0 to 5.8 +/- 0.5 microl/min, U(Na)V from 1.08 +/- 0.31 to 0.43 +/- 0.10 microeq/min, GFR from 1.84 +/- 0.12 to 1.05 +/- 0.06 ml/min (-46.9 +/- 2.7% from baseline), and RPF from 8.62 +/- 0.87 to 3.82 +/- 0.16 ml/min (-54 +/- 3.5% from baseline). When the animals were pretreated with either ABT-627 or A-192621, given alone or combined, the adverse effects of IAP on GFR, RPF, V, and U(Na)V were significantly augmented. When the animals were pretreated with nitroglycerine, the adverse effects of pneumoperitoneum on GFR and RPF were substantially improved. In contrast, pretreatment with N(G)-nitro-L-arginine methyl ester remarkably aggravated pneumoperitoneum-induced renal dysfunction. In conclusion, decreased renal excretory function and hypofiltration are induced by increased IAP. These effects are related to impairment of renal hemodynamics and could be partially ameliorated by pretreatment with nitroglycerine and aggravated by NO and ET blockade.     

Renal effects of dopamine and dopexamine in the newborn anesthetized rabbit.

The renal effects of dopexamine, a new dopaminergic agonist with marked beta 2-adrenergic agonist properties, but no alpha-adrenergic effect, has been studied in 8 newborn New Zealand rabbits, whose renal functional characteristics show close similarities with those of premature infants. Six animals were used as controls. After a control period, dopexamine was infused intravenously at a rate of 4 micrograms/kg per min and after a wash-out period, at 10 micrograms/kg per min. The renal effects of dopamine were studied in similar conditions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by inulin and para-aminohippuric acid clearances, respectively. Dopexamine, 4 micrograms/kg per min, did not induce changes in cardiovascular and renal hemodynamics or in renal functions. At 10 micrograms/kg per min, a significant increase in urine flow rate (25 +/- 5%; p less than 0.01), urine sodium excretion (77 +/- 17%; p less than 0.01) and fractional sodium excretion (69 +/- 25%; p less than 0.05) was observed. The GFR, RPF and renal vascular resistance (RVR) were not affected. Heart rate increased slightly but significantly (8 +/- 3%; p less than 0.05), without change in mean blood pressure (MBP). Dopamine, 4 micrograms/kg per min, decreased slightly albeit significantly MBP (3 +/- 1%; p less than 0.05). At 10 micrograms/kg per min the only renal effect was a significant increase in RVR (19 +/- 6%; p less than 0.02). The different actions of these two dopaminergic agonists in this immature model could be explained by their respective ability to activate electively the adrenergic and dopaminergic peripheral receptors. The natriuretic and diuretic effect of dopexamine in normal immature rabbits, in the absence of changes in RPF or GFR is probably mediated by a direct action of this agent on dopaminergic tubular receptors. Failure of these two drugs to increase RPF may be related to an immaturity of the dopaminergic vascular receptors.     

p22phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats

Angiotensin II (ANG II) infusion increases renal superoxide (O(2)(-)) and enhances renal vasoconstriction via macula densa (MD) regulation of tubuloglomerular feedback, but the mechanism is unclear. We targeted the p22(phox) subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with small-interfering RNA (siRNA) to reduce NADPH oxidase activity and blood pressure response to ANG II in rats. We compared single nephron glomerular filtration rate (SNGFR) in samples collected from the proximal tubule (PT), which interrupts delivery to the MD, and from the distal tubule (DT), which maintains delivery to the MD, to assess MD regulation of GFR. SNGFR was measured in control and ANG II-infused rats (200 ng.kg(-1).min(-1) for 7 days) 2 days after intravenous injection of vehicle or siRNA directed to p22(phox) to test the hypothesis that p22(phox) mediates MD regulation of SNGFR during ANG II. The regulation of SNGFR by MD, determined by PT SNGFR-DT SNGFR, was not altered by siRNA in control rats (control + vehicle, 13 +/- 1, n = 8; control + siRNA, 12 +/- 2 nl/min, n = 8; not significant) but was reduced by siRNA in ANG II-treated rats (ANG II + vehicle, 13 +/- 2, n = 7; ANG II + siRNA, 7 +/- 1 nl/min, n = 8; P < 0.05). We conclude that p22(phox) and NADPH oxidase regulate the SNGFR during ANG II infusion via MD-dependent mechanisms.     

Effects of 30 day simulated microgravity and recovery on fluid homeostasis and renal function in the rat

Transition from a normal gravitational environment to that of microgravity eventually results in decreased plasma and blood volumes, increasing with duration of exposure to microgravity. This loss of vascular fluid is presumably due to negative fluid and electrolyte balance and most likely contributes to the orthostatic intolerance associated with the return to gravity. The decrease in plasma volume is presumed to be a reflection of a concurrent decrease in extracellular fluid volume with maintenance of normal plasma-interstitial fluid balance. In addition, the specific alterations in renal function contributing to these changes in fluid and electrolyte homeostasis are potentially responding to neuro-humoral signals that are not consistent with systemic fluid volume status. We have previously demonstrated an early increase in both glomerular filtration rate and extracellular fluid volume and that this decreases towards control values by 7 days of simulated microgravity. However, longer duration studies relating these changes to plasma volume alterations and the response to return to orthostasis have not been fully addressed. Male Wistar rats were chronically cannulated, submitted to 30 days head-down tilt (HDT) and followed for 7 days after return to orthostasis from HDT. Measurements of renal function and extracellular and blood volumes were performed in the awake rat.     

Renal function of rats in response to 37 days of head-down tilt

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.     

Relaxin-induced changes in renal sodium excretion in the anesthetized male rat

Pregnancy is associated with profound changes in renal hemodynamics and electrolyte handling. Relaxin, a hormone secreted by the corpus luteum, has been shown to induce pregnancy-like increases in renal blood flow and glomerular filtration rate (GFR) and alter osmoregulation in nonpregnant female and male rats. However, its effects on renal electrolyte handling are unknown. Accordingly, the influence of short (2 h)- and long-term (7 day) infusion of relaxin on renal function was determined in the male rat. Short term infusion of recombinant human relaxin (rhRLX) at 4 microg.h(-1).100 g body wt(-1) induced a significant increase in effective renal blood flow (ERBF) within 45 min, which peaked at 2 h of infusion (vehicle, n = 6, 2.1 +/- 0.4 vs. rhRLX, n = 7, 8.1 +/- 1.1 ml.min(-1).100 g body wt(-1), P < 0.01). GFR and urinary excretion of electrolytes were unaffected. After a 7-day infusion of rhRLX at 4 microg/h, ERBF (1.4 +/- 0.2 vs. 2.5 +/- 0.4 ml.min(-1).100 g body wt(-1), P < 0.05), urine flow rate (3.1 +/- 0.3 vs. 4.3 +/- 0.4 microl.min(-1).100 g body wt(-1), P < 0.05) and urinary sodium excretion (0.8 +/- 0.1 vs. 1.2 +/- 0.1 micromol.min(-1).100 g body wt(-1), P < 0.05) were significantly higher; plasma osmolality and sodium concentrations were lower in rhRLX-treated rats. These data show that long-term relaxin infusion induces a natriuresis and diuresis in the male rat. The mechanisms involved are unclear, but they do not involve changes in plasma aldosterone or atrial natriuretic peptide concentrations.     

兔室旁核对血量扩张引起促纳排泄与利尿的作用

在室旁核 (PVN)假损毁兔与PVN损毁兔血量扩张 (VE)引起尿流量增加 ,峰值分别为 0 5 9± 0 0 9与0 3 1± 0 0 3ml/min (P <0 0 1) ,排钠量增加峰值分别为 66 76± 6 74与 3 6 0 5± 3 4 4μmol/min (P <0 0 1) ,而在PVN假损毁兔与PVN完好兔对VE的反应无显著差别 (P >0 0 5 ) ,表明PVN损伤可明显减弱VE引起的促钠排泄与利尿效应。颈迷走神经切断并不能改变PVN损伤的上述作用。双侧肾神经切断兔损毁PVN对VE引起促钠排泄效应无显著影响 ,但显著减弱其利尿效应 (P <0 0 2 )。PVN损毁对VE时肾小球滤过率 (GFR)与肾血浆流量 (RPF)无显著影响。结果表明PVN参与VE通过迷走传入神经引起促钠排泄与利尿反应的调节 ,而肾交感传出神经参与其中促钠排泄的作用