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Background/Aims: To assess the possible contribution of the β-adrenergic overstimulation in early stages of renal injury, the present study evaluated, in rats, the effects of the β-adrenoceptor agonist isoproterenol (ISO) on renal function and morphology, as well as the renal mRNA and protein expression of the NADPH oxidase isoform 4 (Nox 4) and subunit p22phox, endoplasmic reticulum (ER) stress, pro-inflammatory, pro-apoptotic and renin-angiotensin system (RAS) components. Methods: Wistar rats received ISO (0.3 mg.kg-1.day-1 s.c.) or vehicle (control) for eight days. At the end of the treatment, food and water intake, urine output and body weight gain were evaluated and renal function studies were performed. Renal tissue was used for the morphological, quantitative PCR and immunohistochemical studies. Results: ISO did not change metabolic parameters or urine output. However it induced a decrease in renal blood flow and an increase in the filtration fraction. These changes were accompanied by increased cortical mRNA and protein expression for the renal oxidative stress components including Nox 4 and p22phox; ER stress, pro-inflamatory, pro-apoptotic as well as RAS components. ISO also induced a significant increase in medullar renin protein expression. Conclusion: These findings support relevant information regarding the contribution of specific β-adrenergic hyperactivity in early stage of renal injury, indicating the reactive oxygen species, ER stress and intrarenal RAS as important factors in this process.

Acute kidney injury (AKI) continues to be a major therapeutic challenge. Despite significant advances made in cellular and molecular pathophysiology of AKI, major gaps in knowledge exist regarding the changes in renal hemodynamics and oxygenation in the early stages and through the continuum of AKI. Particular features of renal hemodynamics and oxygenation increase the susceptibility of the kidney to sustain injury due to oxygen demand-supply mismatch and also play an important role in the recovery and repair from AKI as well as the transition of AKI to chronic kidney disease. However, lack of well-established physiological biomarkers and noninvasive imaging techniques limit our understanding of the interactions between renal macro and microcirculation and tissue oxygenation in AKI. Advances in our ability to assess these parameters in preclinical and clinical AKI will enable the development of targeted therapeutics to improve clinical outcomes.

Background/Aims: Acute kidney injury (AKI) during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU), has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP) depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF); nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI. Methods: We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI. Results: The present results revealed that the nicotinamide adenine dinucleotide (NAD+) pool and the ATP/adenosine diphosphate (ADP) ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER%) and decreased renal oxygen consumption (VO2). Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered. Conclusion: These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.

Background/Aims: Cigarette smoking is a risk factor for renal damage, but little is known about subclinical effects of smoking on renal hemodynamics and parameters of renal function in humans. We examined the associations of smoking with systemic and renal hemodynamics and renal function parameters in healthy individuals. Methods: Data from 196 potential living kidney donors were analysed retrospectively. Mean arterial blood pressure (MAP), effective renal plasma flow (ERPF) and creatinine clearance had been measured. We additionally calculated parameters of renal hemodynamics. Data were analyzed for the effects of smoking and sex dependent on age and MAP. Results: Systemic and renal hemodynamic parameters did not differ between smokers and non-smokers. In non-smokers of both sexes MAP was negatively correlated with ERPF, and higher MAP was associated with increased renal vascular resistance and with afferent arteriolar resistance, with glomerular pressure (PG) remaining constant. However, in male, but not in female smokers, ERPF and PG increased with MAP. A correlation of age with a steeper decline in ERPF in male smokers was lost in multiple regression analysis. Conclusions: As compared to women, smoking men may exhibit an increased glomerular hydrostatic pressure, which is a known promoter of kidney damage.

Background/Aims: Despite extensive studies, the intracellular regulatory mechanism of renin production and release is still poorly understood. The present study was designed to test whether CD38-ADP-ribosylcyclase signaling pathway contributes to the regulation of renin production and release, and to examine whether CD38 gene knockout (CD38 -/- ) can change this important renal endocrinal function. Methods: ADP–ribosylcyclase activity was estimated utilizing HPLC, cADPR levels from western blot, plasma renin activity from RIA kit, urinary sodium and potassium excretion from flame photometry. Results: The expression of CD38 and the activity of ADP-ribosylcyclase to produce cyclic ADP-ribose (cADPR) were nearly abolished in the kidney from CD38 -/- mice, indicating that CD38 gene is a major enzyme responsible for the generation of cADPR in vivo. Mice lacking CD38 gene showed increased plasma renin activity (PRA) in either conscious or anesthetized status (P

The aim of this paper was to study the effects of essential fatty acid (EFA) on fractional sodium excretion (FENa+) and renal hemodynamics in rats during hydropenia (H) and acute volume expansion (VE), successively. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured using a blood pressure transducer and a flow probe, respectively, both connected to a flowmeter. Glomerular filtration rate (GFR) was estimated by inulin clearance. The rats receiving coconut oil as only source of dietary lipids (the EFA-deficient group) presented lower levels of linoleic acid in cortex and medulla and lower body weight than the rats receiving soy oil in place of coconut oil (the control non-EFA-deficient group). During H, the EFA-deficient rats exhibited a lower level of renal vascular resistance resulting in a higher level of RBF and a higher urinary flow (V’) and FENa+, although GFR was lower than in the control group. During VE, the rats of the control group responded with increased MAP, RBF, V’ and FENa+, which were not found in the EFA-deficient group, suggesting an impaired hemodynamic adjustment in EFA deficiency. In conclusion, both experimental conditions revealed that EFA deficiency affects the renal hemodynamics.

Background/Aims: To gain insight into the effect of arginine vasopressin (AVP) on renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive response to AVP on total renal blood flow (RBF) and total and zonal glomerular filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was tested. Methods: Total RBF and total and zonal GFR were studied in 10- and 40-week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a flowmeter before infusion of AVP and immediately after injection of a bolus dose of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by the tubular uptake of 125I- and 131I-labelled aprotinin before and during a continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular V1a receptors were performed in young and old rats. Results: RBF decreased by 43 ± 3% in 10-week SHR (9.2 ± 0.5 vs. 5.2 ± 0.3 ml·min–1·g–1), significantly more than 10-week WKY where RBF decreased by 35 ± 3% (9.6 ± 0.7 vs. 6.5 ± 0.5 ml·min–1·g–1) (p < 0.05). The effect of AVP on RBF was attenuated in 40-week-old rats where the decline in RBF was 29 ± 5% in SHR and 23 ± 4% in WKY (p > 0.05). GFR decreased by 6 ± 3% (1.03 ± 0.04 vs. 0.96 ± 0.04 ml·min–1·g–1, p < 0.05) in 10-week SHR and was unchanged in 10-week WKY (1.10 ± 0.07 vs. 1.08 ± 0.04 ml·min–1·g–1, p > 0.10). GFR decreased by 11 ± 10% in 40-week SHR and by 4 ± 4% in 40-week WKY (p > 0.05). AVP infusion significantly increased filtration fraction in all groups except 40-week SHR, indicating that AVP has the strongest vasoconstrictive effect on postglomerular vessels. The intrarenal distribution of GFR was unchanged in the normotensive and hypertensive groups. V1a receptor density was upregulated in young SHR compared to young WKY (p < 0.05), but downregulated in old compared to young SHR (p = 0.05). Conclusion: The results indicate that AVP sensitivity is not increased in the juxtamedullary cortex in SHR and the reduced vasoconstrictive effect in old SHR is due to a reduced density of V1a receptors.

Background/Aims: A diet rich in polyunsaturated Ω3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short– and long–term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. Methods: Eight rats each were pairfed FO– versus cholesterol–enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2–week trial: 1 rat on the FO and 1 rat on the control diet; 32–week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. Results: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75±2.19 vs. 6.87±1.91 ml/min/g, p2/thromboxane B2 ratio shifted towards the vasodilatative prostaglandin E2 (1.76±0.18 vs. 0.91±0.19, pConclusion: The short–time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.

The effect of aging on the physiologic responses of renal plasma flow (RPF) and glomerular filtration rate to an acute oral protein load (renal reserve) is a poorly understood process. In this study of 37 healthy human volunteers, distributed among three groups (group 1: n = 13, age range 20–39 years; group 2: n = 13, age range 40–59 years; group 3: n = 11, age range 60–68 years), we evaluated the influence of age on some of the vasoactive systems such as plasma renin activity, urinary kallikrein, plasmatic prokallikrein, plasmatic kallikrein, and plasmatic kininogen on RPF and creatinine clearance (Ccr) in response to an acute oral protein load (1 g/kg body weight). The aging process diminished but did not cease the increments in RPF (group 1: 539.6 vs. 658.9 ml/min/1.73 m2, p < 0.001; group 2: 509.0 vs. 570.7 ml/min/ 1.73 m2, p < 0.001; group 3: 453.9 vs. 506.0 ml/min/ 1.73 m2, p < 0.001) and Ccr (group 1: 139.7 vs. 166.5 ml/ min/1.73 m2, p < 0.001; group 2: 126.6 vs. 142.2 ml/min/1.73 m2, p < 0.001; group 3: 112.6 vs. 121.4 ml/min/ 1.73 m2, p < 0.01) after a protein overload. The plasma renin activity did not change after a meat meal. On the other hand, all parameters regarding the kinin system changed significantly in the direction of increased bradykinin formation, despite aging (urinary kallikrein – group 1: 0.25 vs. 0.44 mU/ml, p < 0.005; group 2: 0.25 vs. 0.41 mU/ml, p < 0.005; group 3: 0.33 vs. 0.47 mU/ml, p < 0.005/plasmatic kininogen – group 1: 1.3 vs. 0.9 µg LBK/ml, p < 0.005; group 2: 1.1 vs. 0.7 µg LBK/ml, p < 0.005; group 3: 0.8 vs. 0.7 µg LBK/ml, p < 0.005). These findings indicate that: (1) the aging process narrows but does not cease the increment range in Ccr and RPF after acute oral protein ingestion; (2) increased bradykinin formation plays a definite role in the acute renal vasodilatory response, and (3) contrary to previous clinical studies, our results suggest that the renal reserve is progressively and significantly reduced during the aging process.

The effect of extracorporeal shock wave lithotripsy (ESWL) with an MPL9000 lithotriptor on renal hemodynamics and urine flow was investigated by 99mTc-DTPA renal scintigraphy. In the first

With improvements in short-term renal transplant survival, concerns regarding the long-term outcome are becoming more important. Chronic rejection is the single most important cause of graft failure in the first posttransplant decade, but its pathophysiology remains poorly understood. It has been suggested that chronic rejection is the tissue remodelling that is initiated by smoldering foci of inflammation initiated by acute rejection episodes, perhaps in conjunction with chronic rejection-specific allogeneic immune reaction. The chronicity of these processes leads to concurrent activation of tissue repair mechanisms and changes in renal hemodynamics, which contribute to the tissue remodelling that is characteristic for chronic rejection.

Renal hemodynamics and function were assessed in 10 anesthetized newborn rabbits undergoing acute hyperoxemia for 1 h. The hyperoxemic period either followed (group 1; n = 5) or preceded (group 2; n = 5) a normoxemic control period. Renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by the clearance of p-aminohippuric acid and inulin, respectively. Urine flow rate, GFR, RBF, renal vascular resistance, filtration fraction and sodium fractional excretion remained unchanged throughout the study whatever the order of the normoxemic and hyperoxemic periods. It is concluded that hyperoxemia up to PaO2 of 170 mm Hg does not alter renal function.

The purpose of the present experiments was to determine the renovascular effects of the adenosine agonists N-ethyl-carboxamide adenosine (NECA), N6-cyclohexyl adenosine (CHA) and 2-chloro adenosine (2-CLA). The diameter of pre- and postglomerular vessels in the split hydronephrotic kidney of Inactin®-anesthetized rats was measured by in vivo television microscopy. All metabolically stable adenosine agonists were topically applied into the renal tissue bath. NECA, a preferential A2 adenosine receptor agonist, induced dose-dependent marked pre- and slight postglomerular vasodilation except for a small constrictory effect on the afferent arteriole near the glomerulus. Application of CHA, a selective A1 adenosine receptor agonist, led to a vasoconstriction of all preglomerular vessels, the extent of which was greatest at the most distal segment of the afferent arteriole. 2-CLA, a nonselective agonist, produced a small decrease in diameter in all preglomerular vessels, a marked constriction of the afferent arteriole at sites near the glomerulus, and a slight dilation of postglomerular vessels. Glomerular blood flow (GBF) was increased by NECA, and decreased by CHA and 2-CLA. The effects of CHA in reducing GBF were greater than those of 2-CLA. From these experiments it is concluded that vascular A1and A2 adenosine receptors are present in the kidney and that activation of A1 receptors is associated with preglomerular vasoconstriction only, whereas activation of A2 receptors mediates pre- and postglomerular vasodilation with a lack of vasodilatory response of the distal afferent arteriole. Furthermore, these data indicate that nonselective occupation of both receptor subclasses is associated with marked vasoconstriction of the afferent arteriole and little vasodilation of the efferent arteriole.

The effects of the beta-adrenoceptor-blocking drugs tertatolol and propranolol on regional hemodynamics were compared in intact and sinoaortic denervated (SAD) conscious spontaneously hypertensive rats (SHR). Miniaturized Doppler flow probes were used for the continuous determination of changes in flows and resistances in the renal, mesenteric, and hindquarter vascular beds. In intact animals 5 mg/kg propranolol i.v. caused an initial increase and a later gradual fall in mean arterial blood pressure (MAP) and an early rise in all three resistances. In SAD rats the reduction in MAP occurred more readily and no increases in RR and MR were observed. RR even decreased significantly. 0.5 mg/kg tertatolol i.v. caused a similar change in MAP as did propranolol. In contrast, tertatolol increased resistance only in the hindquarter vascular bed, both in intact and SAD animals. These data show an important role of sinoaortic baroreflex activation in the early peripheral vasoconstriction caused by propranolol in conscious SHR. Moreover, the data suggest that tertatolol inhibits the sympathetic nervous system-mediated reflex vasoconstriction.

The effect of prednisone therapy on renal hemodynamics was studied in normal, autotransplanted as well as homotransplanted dog kidneys. After intravenous administration of prednisone (8 and 16 mg/kg/min) the total blood flow decreased and vascular resistance increased significantly. This effect was more pronounced if the drug was directly injected into the arteria renalis. The same changes were observed in autotransplanted and homotransplanted kidneys and in kidneys in rejection. Our results suggest that high dosage of prednisone decreases the renal blood flow and this adverse effect has to be considered in the therapy. The administration of the drug directly into the arteria renalis may have to be avoided.

The effect of captopril (SQ 14,225) on the renal hemodynamics, cortical plasma flow (CPF) and noncortical plasma flow (NCPF), was studied in sodium-replete anesthetized dogs during aprotinin infusion. Mean blood pressure (MBP) increased by aprotinin (p less than 0.05) and decreased by captopril (p less than 0.02). Renal vascular resistance (RVR) tended to increase by aprotinin and decreased from 1.29 to 0.86 mm Hg/ml/h (74.7%) by captopril (p less than 0.05). Renal vein renin activity (RRA) inclined to decrease by aprotinin and increased from 17.8 to 47.2 ng/ml/h (278.2%) by captopril (p less than 0.05). Although the administration of captopril alone did not alter the renal hemodynamics despite the reduction of MBP, captopril made a recovery of renal plasma flow (RPF), CPF and NCPF which had decreased by aprotinin. Especially, CPF showed a significant recovery from 45.4 to 55.6 ml/min (123.6%) by captopril (p less than 0.02). These results indicate that the inhibition of endogenous angiotensin made a preferential increase in CPF and suggest that the renin-angiotensin system plays a major role in the effect of captopril of the renal hemodynamic changes.

Renal hemodynamics following administration of the angiotensin II antagonist Saralasin were studied in untouched kidney of 11 two-kidney hypertensive rats and in kidneys of 7 control rats using an electromagnetic flowmeter. Renal blood flow (RBF) in controls averaged 6.2 +/- (SD) 1.7 vs. 5.2 +/- 0.9 ml/min/g kidney weight in the hypertensive group (n.s.). Renal vascular resistance (RVR) was significantly increased in untouched kidneys: 2.6 +/- 0.5 vs. 1.8 +/- 0.4 dyn . sec . cm-5 . 10(6) . g kidney weight-1. Following Saralasin infusion mean arterial blood pressure decreased significantly more in hypertensive rats. RBF increased by 24% in untouched kidneys vs. 12% in controls (p0.05), indicating a 34% decrease of RVR in hypertensive rats vs. 18% (p0.005) in controls. These results indicate that the increased RVR in untouched kidneys is highly dependent on circulating angiotensin II, which may reduce the antihypertensive role of the untouched kidney.

We have examined the effects of erythrocytes on the function and morphology of isolated rat kidneys perfused with a physiological concentration of bovine albumin (45 g/l). (1) In kidneys perfused without red cells, renal vascular resistance (RVR) was low (4.2 ± 0.3 mm Hg/ml/min/g), fractional sodium excretion (FeNa) was high (14.5 ± 1.8%) and concentrating ability impaired (maximum urine osmolality 343 ± 4 mmol/kg). The erythrocyte-free kidney also developed necrosis of the cells of the medullary thick ascending limb (mTAL). (2) Erythrocytes at a hematocrit of 4–6% did not alter RVR but prevented ischemic changes in the mTAL and reduced FeNa to 9.4 ± 0.03%. Concentrating ability was not improved by a hematocrit of 4–6% despite the presence of a morphologically normal mTAL. (3) At a hematocrit of 40–45%, RVR was increased (to 11.2 ± 0.4 mm Hg/ml/min/g) and FeNa was further lowered to 3.5 ± 0.6%. Also, urinary concentrating ability was markedly improved (maximum urine osmolality 640 ± 35 mmol/kg). (4) The isolated perfused kidney (IPK) at a hematocrit of 40–45% was able to autoregulate renal perfusate flow rate of GFR but auto-regulation was incomplete. A 50% increase in perfusion pressure from 100 to 150 mm Hg increased renal perfusate flow rate and GFR 27 and 29%, respectively. Thus the IPK is not able to autoregulete as efficiently as the kidney in vivo, even in the presence of red cells at a normal hematocrit.

Most previous studies using the isolated perfused kidney model to assess the mechanisms governing renin release have utilized single-point determinations of media renin content as an estimate of renin release rate. In the present study the dynamics of renin release were examined under standardized conditions of perfusion, with simultaneous evaluations of changes in renal function. Media samples were collected at 5-min intervals. Renin release rate was characterized by an initial progressive increase which achieved a constant value of 67 ng/ h/min/g only after 45 min of perfusion. Consequently, the accumulation of renin within the media does not become linear until 45 min of perfusion. Simultaneous determinations of various parameters of renal function disclosed that neither GFR, renal sodium handling nor indices of distal delivery correlated with renin release. However, the renin-angiotensin system is not physiologically intact since the standard perfusate utilized in the present study was demonstrated to lack both renin substrate and converting enzyme. The present studies demonstrate that renin release is curvilinear and that experimental errors may occur if sampling is not restricted to the stable phase of perfusion.

We followed renal function through the natriuretic phase of 6 occasions of drug-induced recovery from minimal lesions nephrotic syndrome (MLNS). Protein excretion started to fall 1-3 days prior to the start of the natriuresis. The natriuresis was accompanied by a rise in glomerular filtration rate (GFR, inulin clearance). The filtration fraction, calculated from the GFR and the p-aminohippurate clearance, rose steadily in 5 subjects in whom it was low before therapy. Proximal and distal sodium reabsorption fractions, estimated from the changes in maximum free water clearance, fell, and fractional sodium, lithium, uric acid and free water clearance rose. At the time of these changes plasma protein had hardly risen, whereas renin activity was down. These results are in agreement with the notion that the sodium retention of MLNS is due to a renal defect. Repair of the glomerular filter, evident from the disappearance of proteinuria and the rise in filtration fraction, apparently normalizes the elevated tubular sodium reabsorption proximal to the macula densa, which leads to a fall in renin release.

To test whether angiotensin (All) induces proteinuria via its effect on renal hemodynamics, or by another mechanism, two experimental approaches were used. In the first, it was found that All was as effective in inducing proteinuria in nephrotic as in intact rats. In all All augmented proteinurias, filtration fraction was increased. These effects plus electrophoretic profiles of All proteinuria in intact rats suggested that hemodynamic changes underly the increased glomErular permeability to protein. In the second approach, the All inhibitor, sar-ala-angiotensin, does not itself induce proteinuria or changes in GFR and RPF, but prevented the hemodynamic responses to All and the proteinuric response as well.

Experiments were performed in anesthetized Macaca fascicularis monkeys to examine the renal hemodynamic responses of these animals to a 15% blood volume expansion using isooncotic dextran in isotonic saline. 20 min following the onset of volume expansion, effective renal plasma flow had increased 80%, glomerular filtration rate was unchanged from control and filtration fraction had decreased 34%. At 50 min, effective renal plasma flow was still increased 74%, glomerular filtration rate had increased 39% and filtration fraction remained decreased 24%. These disproportionate changes in renal plasma flow and glomerular filtration rate are similar to the reported effects in man. Furthermore, they would suggest that glomerular filtration in the primate may not be highly plasma flow dependent under these conditions.

Tertatolol is a noncardioselective beta-adrenergic blocking agent without partial agonist activity. Its central and renal hemodynamic effects were compared to those of an equipotent dosage of propranolol in two groups of 10 patients each who developed arterial hypertension and a hyperdynamic circulatory state after head injury. After tertatolol, 5 mg orally, mean arterial blood pressure was unaffected, heart rate decreased by 22% (p less than 0.01) and cardiac index by 24% (p less than 0.01) while renal blood flow remained unchanged (-5%; not significant) so that the renal fraction of cardiac index was increased by 22% (p less than 0.05). After propranolol, 160 mg orally, mean arterial blood pressure was not modified, heart rate decreased by 12% (p less than 0.01), cardiac index by 16% (p less than 0.01) and renal blood flow by 17% (p less than 0.01) so that the renal fraction of cardiac index remained unchanged (-3%; not significant). Tertatolol is a potent beta-blocking agent comparable to propranolol apart from the fact that it preserves renal perfusion; this peculiar effect is related to a redistribution of the reduced cardiac output to the benefit of the kidney.

We report 5 cases of acute reversible renal failure coinciding with the onset of treatment with captopril in patients with severe drug-resistant hypertension. There was no clinical or laboratory evidence for an immunologic or toxic insult, although in 1 patient we found a transient leukocyturia and mild proteinuria. A mere hypoperfusion of the kidney does not seem sufficient to account for all 5 observations: in 3 of them changes in blood pressure did not parallel changes in renal function. We propose that, in addition to hyperperfusion, captopril alters renal function by an additional intrarenal hemodynamic effect. The 5 patients had severe renovascular disease which might thus represent a significant risk factor in the development of captopril-induced acute renal failure.

Systemic hemodynamic impairment (hepatocirculatory failure) has been suggested as one of the possible factors which may explain the renal hemodynamic alterations found in the late stage of liver cirrhosis, typical of the hepatorenal syndrome. 20 patients, divided into two groups of 10 sodium retainers and 10 sodium excretors, affected by liver cirrhosis with portal hypertension and ascites, were studied. Renal functional parameters (diuresis, urinary and plasma electrolytes, urine to plasma osmolality and creatinine ratios and creatinine clearance) were evaluated before and after acute volume expansion with 1,000 ml of 10% dextran in saline, infused through a catheter located in the right atrium. Hemodynamic tests (cardiac index, systemic vascular resistance, right atrial pressure and capillary wedge pressure) were performed before, during and after expansion. Cardiac index decreased in 6 patients (sodium excretors) after a 500-ml infusion and rose again after 1,000 ml in 5 of them. The remaining 14 patients showed a progressive and significant increase of cardiac index. A strong inverse relationship between cardiac index and systemic vascular resistance was observed (r = -0.87; p less than 0.001). The mean left-ventricular function curve showed a slow response in most sodium excretors and a normal response in the sodium-retaining group, without significant difference between the two groups. Sodium excretion significantly improved after expansion in both groups of patients. No relationship was found between hemodynamic response and renal function. These data show that cardiocirculatory function is normal, even in sodium-retaining cirrhotics.

Systemic and renal hemodynamics, and plasma antinatriferic activity (AA) were measured before, during 2 h of saline loading, and for 1 h immediately after stopping saline infusion in dogs. During loading, mean arterial pressure (MAP), central venous pressure (CVP), renal blood flow (RBF), glomerular filtration rate (GFR), and AA increased as sodium excretion as (UNaV) rose progressively. During the post-loading period, MAP, CVP, and AA returned to baseline, RBF and GFR remained elevated, while UNaV fell. Only 52 ± 3% of the total sodium load was excreted during the study. These data show that AA is not regulated by the absolute volume of extracellular fluid. The correlation of AA with changes in systemic hemodynamics suggests ‘volume receptors’ in the resistance and/or capacitance circulation. The data suggest that the post-loading fall in UNaV is due at least in part to decreased levels of a humoral natriuretic factor.