Handling of ammonium by the renal proximal tubule during acute metabolic acidosis

The present studies were designed to assess the handling of ammonium (NH+4) by the proximal tubule during acute metabolic acidosis (AMA). After tubule fluid collections were obtained with micropuncture techniques and in situ pH was determined near the end of the proximal tubule, 0.2 N HCl was infused intravenously at 17 microliter X min-1 X 100 g body wt-1. Thirty to sixty minutes later, samples were obtained and pH measurements were made near the previous micropuncture sites. During AMA, urine pH fell and total acid excretion doubled due to an increase in NH+4 excretion from 581 +/- 63 to 1,153 +/- 61 nmol X min-1 X g kidney wt-1 (P less than 0.001). Acid excretion did not change in time controls. Tubule fluid NH+4 rose from 2.17 +/- 0.15 to 3.45 +/- 0.24 mM during acid infusion (P less than 0.001) and its delivery to the end of the proximal tubule nearly doubled (67.8 +/- 6.3 vs. 33.9 +/- 2.9 pmol X min X g kidney wt-1 before acid infusion, P less than 0.001). This increase in delivery during AMA was due to enhanced ammonia (NH3) entry into the proximal tubule. In situ pH determined near the end of the proximal tubule averaged 6.94 +/- 0.04 before acid infusion and did not change afterwards (6.87 +/- 0.05). These data are consistent with the hypothesis that in AMA the increase in NH+4 excretion is due primarily to an increase in the cortical production of NH3.     

Loss of residual renal function in patients on regular haemodialysis

The literature offers scant data on loss of residual renal function in chronic haemodialysis patients. The present study was undertaken in 34 patients, to evaluate residual creatinine clearances (CCr) before the start of haemodialysis and after 3, 12 and 24 months. CCr progressively declined from 6.15 +/- 2.61 (before) to 1.40 +/- 1.29 ml.min-1 (after 24 months: p less than 0.01). The decrease was largest during the first three months of dialysis therapy (slope -0.99 +/- 1.01 ml.min-1.month-1 for the first three months vs. -0.23 +/- 0.12 ml.min-1.month-1 for the entire 24-month period: p less than 0.01). The decline in CCr during the first three months was significantly more pronounced in glomerular disease than in tubulo-interstitial disease (p less than 0.05). This could not be attributed to differences in blood pressure, body weight or hypotensive medications. Age and sex also had no influence. Our data indicate that there is a characteristic progressive loss of renal function in haemodialyzed patients and that the early decline is most pronounced in patients with glomerular disease. Regular assessment of residual renal function at least every three months is indicated in patients starting chronic haemodialysis treatment.     

Dissociation between pancreatic islet blood flow and insulin release in the rat

The blood flow to the pancreatic islets was estimated with the aid of microspheres in fed or starved (72 h) rats. The total pancreatic blood flow (PBF) in fed animals was 0.55 +/- 0.04 ml X min-1 X g pancreas and in the starved animals 0.30 +/- 0.04 ml X min-1 X g pancreas (P less than 0.001), and the corresponding islet blood flow (IBF) 82.0 +/- 12.4 and 50.5 +/- 9.7 microliter min-1 X g pancreas respectively (P greater than 0.05). Intraperitoneal injection of 2 ml of a 30% glucose solution caused a marked increase in IBF in both fed (P less than 0.05) and starved (P less than 0.01) animals to approximately the same level. The circulating insulin concentration remained unaffected by glucose in the starved rats but increased (P less than 0.001) in the fed rats, indicating that insulin release does not necessarily rise in parallel with an elevated IBF. Intraperitoneal injection of 2 ml of a 30% solution of mannoheptulose, an inhibitor of islet glucose metabolism, decreased the serum insulin concentrations although the serum glucose concentrations rose significantly in both fed (P less than 0.001) and starved (P less than 0.001) animals. This treatment, however, caused both IBF and PBF to increase significantly in both groups. The data support the view that islet blood flow is not necessarily related to the metabolic status of the islet cells or to the insulin release.     

The influence of Atriopeptins I and II on the relationship between glomerular filtration and natriuresis

The effects of two pure synthetic atrial natriuretic factors, Atriopeptin (AP) I and AP II, on the whole kidney glomerular filtration rate (GFR), sodium and potassium excretion (UNaV, UKV), urine flow rate (V) and arterial blood pressure (BP) were studied in adult male Sprague-Dawley rats. The variables were measured during a control period and during 70 min of continuous intravenous infusion of AP I or AP II at a rate of 10 micrograms h-1 kg-1 body wt. A time control group was studied in parallel to see whether the variables under study changed with time. The AP I infusion did not affect GFR (change from 1.34 +/- 0.10 to 1.24 +/- 0.04 ml min-1 g-1 kidney wt), but was clearly natriuretic (UNaV changed from 0.071 +/- 0.011 to 0.229 +/- 0.038 mumol min-1 g-1 kidney wt, P less than 0.01). The UKV increased from 0.504 +/- 0.073 to 1.138 +/- 0.121 mumol min-1 g-1 kidney wt, (P less than 0.001) and V from 1.88 +/- 0.10 to 2.94 +/- 0.15 microliter min-1 g-1 kidney wt, (P less than 0.001). Urine osmolality (Uosm) and BP were unaffected. During AP II infusion GFR remained unchanged but was slightly below the pre-infusion level during the last infusion period (1.05 +/- 0.07 as against 1.37 +/- 0.09 ml min-1 g-1 kidney wt, P less than 0.05). Despite this fact, UNaV was significantly elevated throughout the infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute reversal by saralasin of multiple intrarenal effects of angiotensin II.

Glomerular hemodynamics were measured by micropuncture technique in the plasma volume-expanded Munich-Wistar rat in 1) a control group, 2) during a pressor infusion of angiotensin II (AII), and 3) during simultaneous infusions of AII and saralasin, which returned arterial pressure to normal. Respective values obtained in the three groups studied were: nephron filtration rate: 60 +/- 2 vs. 40 +/- 2 vs. 42 +/- 2 nl.min-1.g kidney wt-1; nepphron plasma flow: 263 +/- 13 vs. 106 +/- 5 vs. 165 +/- 13 nl. min-1.g kidney wt-1; LpA, the glomerular permeability coefficient: 0.090 +/- 0.009 vs. 0.033 +/- 0.005 vs. 0.103 +/- 0.020 nl.s-1.g kidney wt-1. mmHg-1; afferent arteriolar resistance: 10.2 +/- 0.7 vs. 25.1 +/- 1.3 vs. 19.7 +/- 3.3 10(9) dyn.s.cm-5; efferent arteriolar resistance: 7.8 +/- 0.5 vs. 22.0 +/- 0.9 vs. 10.8 +/- 1.7 10(9) dyn.s.cm-5. Saralasin acutely reversed the effect of AII on both efferent resistance and LpA, suggesting that AII does not decrease LpA by inducing a fixed anatomic change. For unclear reasons, saralasin did not reverse the increase in afferent resistance associated with infusion of AII. Saralasin infusion in high AII states may acutely affect glomerular hemodynamics by decreasing efferent resistance and increasing the glomerular permeability coefficient.     

Canine renal vascular response to hyperoncotic dextran in kidneys with or without glomerular filtration

The effect of intrarenal arterial infusion of hyperoncotic dextran on renal hemodynamics and excretion was studied in anesthetized dogs. To examine the role of glomerular filtration and tubular flow in the hemodynamic response, several kidney models were employed. Nonfiltering kidneys (NFK) were produced by combined ischemia and ureteral obstruction (UO). Additionally, kidneys with only UO and a lack of filtration as well as kidneys with only ischemia and glomerular filtration were studied. Renal blood flow in normal kidneys was increased by hyperoncotic dextran from 357 +/- 47 to 486 +/- 65 ml X min-1 X 100 g-1, with a corresponding decrease in renal vascular resistance. Ischemic kidneys responded likewise to the dextran infusion, increasing renal blood flow from 261 +/- 31 to 339 +/- 29 ml X min-1 X 100 g-1. Glomerular filtration rate was reduced by the dextran infusion from 80.1 +/- 7.9 to 60.7 +/- 6.6 in normal kidneys and from 31.8 +/- 9.6 to 20.2 +/- 5.8 ml X min-1 X 100 g-1 in ischemic kidneys. Urine flow and sodium excretion were also reduced in these kidneys. In contrast, both NFK and UO, which lacked filtration and tubular flow, did not vasodilate in response to dextran. Renal blood flow remained unchanged from control values (NFK: 146 +/- 6, UO: 111 +/- 22 ml X min-1 X 100 g-1) in these kidneys. These experiments show that the renal vascular response to hyperoncotic dextran is not due to a change in blood volume or viscosity nor to a direct pharmacologic action of dextran. The most likely explanation is that hyperoncotic dextran alters tubuloglomerular feedback control of renal vascular resistance by decreasing filtration and altering tubular flow and/or composition. However, the involvement of another intrarenal vasodilatory system cannot be discounted.     

Renal excretion of ascorbic acid in the rat: a micropuncture study

Ascorbate concentration was measured by high-performance liquid chromatography and amperometry in plasma, tubular fluid, and urine from rats infused with ascorbic acid to steady-state levels. At a low concentration of ascorbate in plasma (Pasc = 0.2 mM) reabsorption occurred along the proximal convoluted tubule (PCT). The fractional delivery (FD) of ascorbate [(TF/P)asc/(TF/P)polyfructosan] to the late proximal convoluted tubule was 0.64 +/- 0.04, and the fractional excretion of ascorbate (FEasc) was 0.56 +/- 0.01. At higher Pasc (0.9 mM) net secretion occurred in the PCT, while the FDasc was 1.5 +/- 0.2 to the early and 1.8 +/- 0.2 to the late PCT. At still higher Pasc the secretory and the reabsorptive transports were saturated and the FDasc and FEasc approached unity, indicating that reabsorptive as well as secretory transport occurs in the proximal tubule. In clearance experiments the reabsorptive transport and secretory transport were inhibited by 2-nitroprobenecid. The drug induced a fall of FEasc when infused at a low rate (0.9 mumol X kg body wt-1 . min-1), which was followed by an increase in FEasc when the rate of infusion of 2-nitroprobenecid was increased to 3 mumol . kg body wt-1 X min-1.     

Effects of atrial natriuretic peptide (ANP) during converting enzyme inhibition

Studies were performed on anesthetized adult Münich-Wistar rats to investigate the role of angiotensin II in the natriuretic response to synthetic atrial natriuretic peptide (ANP, 28 amino acids). For this purpose the whole kidney glomerular filtration rate (GFR) and urinary excretion of electrolytes were measured in groups of animals pretreated with the converting enzyme inhibitor captopril (3 mg h-1 kg-1 body wt) or vehicle and then given a continuous intravenous infusion of ANP at 10 micrograms h-1 kg-1 body wt. In the vehicle-pretreated animals, 45 min of ANP infusion did not change GFR (control value 1.17 +/- 0.11, experimental value 1.17 +/- 0.06 ml min-1 g-1 kidney wt). Sodium excretion (UNaV) increased more than three-fold from 0.036 +/- 0.010 to 0.134 +/- 0.058 mumol min-1 g-1 kidney wt (p less than 0.05) and potassium excretion (UKV) increased from 0.481 +/- 0.055 to 0.946 +/- 0.068 mumol min-1 g-1 kidney wt (P less than 0.05). Urine osmolality (UOsm) remained unchanged, while the blood pressure (BP) decreased by 15%. In animals pretreated with captopril, ANP infusion led to a decrease in GFR from 1.27 +/- 0.11 to 1.05 +/- 0.09 ml min-1 g-1 kidney wt (P less than 0.05). Despite this effect, UNaV increased more than two-fold from 0.076 +/- 0.020 to 0.193 +/- 0.087 mumol min-1 g-1 kidney wt (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The dopamine receptor antagonist haloperidol blocks natriuretic but not hypotensive effects of the atrial natriuretic factor

Studies were performed on anesthetized male Münich-Wistar rats to investigate the influence of the dopamine (DA) receptor antagonist haloperidol on the natriuretic response to infusion of a synthetic atrial natriuretic factor. The whole kidney glomerular filtration rate (GFR), urinary excretion of electrolytes, and arterial blood pressure (BP) were therefore measured in groups of animals pretreated with haloperidol or vehicle and given a continuous intravenous infusion of atrial natriuretic peptide (ANP; 28 amino acids). Forty-five minutes of ANP infusion at 10 micrograms h-1 kg-1 body wt did not increase GFR (change from 1.14 +/- 0.08 to 1.15 +/- 0.05 ml min-1 g-1 kidney wt). Sodium excretion (UNaV) increased more than four-fold from 0.037 +/- 0.008 to 0.165 +/- 0.070 mumol min-1 g-1 kidney wt (P less than 0.01). Potassium excretion (UKV) increased by 86% (P less than 0.001) and the urine flow rate (V) increased transiently by 63% (P less than 0.05) and did not differ from the control value during the last 15 min of ANP infusion. The urinary sodium concentration (UNa) increased almost three-fold, while BP decreased by 14%. There was no change in urine osmolality. In animals pretreated with haloperidol (1 mg kg-1 body wt), 45 min of ANP infusion did not significantly alter GFR (from 1.10 +/- 0.08 to 0.98 +/- 0.09 ml min-1 g-1 kidney wt). The UNaV did not increase significantly (change from 0.026 +/- 0.006 to 0.030 +/- 0.009 mumol min-1 g-1 kidney wt). The UKV was not elevated by ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of spinal cord blood flow in the rat as measured by quantitative autoradiography

Spinal cord blood flow (SCBF) and its response to alterations in blood gases and to systemic hypotension, haemodilution and barbiturate anaesthesia were measured in 47 rats at the level of Th 7-8 by quantitative autoradiography with [14C]iodoantipyrine ([14C]IAP) as tracer. During normocapnia and normoxia the mean SCBF values in the grey and white matter were 94 +/- 21 and 17 +/- 3 ml min-1 100 g-1, respectively. SCBF was highly dependent on PaCO2. Thus in hypercapnic animals (PaCO2 greater than 9 kPa) SCBF was increased in grey and white matter to 228 +/- 22 and 54 +/- 7 ml min-1 100 g-1, while during hypocapnia (PaCO2 less than 3.9 kPa) it was decreased to 64 +/- 14 and 11 +/- 2 ml min-1 100 g-1, respectively. Mean arterial blood pressure (MABP) was reduced by withdrawal of blood to 80 +/- 8 mmHg in a light hypotension group and to 53 +/- 11 mmHg in a severe hypotension group, compared with 126 +/- 13 mmHg in a control group. There was no significant difference in SCBF between the control group and the hypotension groups, suggesting that autoregulation is maintained down to an MABP of at least 50 mmHg. Normovolaemic haemodilution, with a reduction of the haematocrit from 50 +/- 2 to 33 +/- 3, increased SCBF to 113 +/- 9 ml min-1 100 g-1 in grey matter and to 21 +/- 12 ml min-1 100 g-1 in white matter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tubular response to hormones is blunted in weanling rats

The renal responses to atrial natriuretic peptide (ANP), parathyroid hormone (PTH) and arginine vasopressin (AVP) were studied in anaesthetized weanling and adult rats with clearance methods. In rats receiving PTH, thyroparathyroidectomy (TPTX) was performed prior to the study. The results showed that GRF remained unchanged in both age groups during infusion with ANP, AVP and PTH after TPTX as well as with TPTX alone. During ANP infusion, the urine flow rate increased from 0.01 +/- 0.002 to 0.029 +/- 0.004 ml (100 g body wt)-1 min-1 (P less than 0.001) and the fractional sodium excretion increased from 0.48 +/- 0.1 to 3.0 +/- 0.4% (P less than 0.001) in the adult rats; no significant changes were observed in the weanling rats. Phosphate excretion was not influenced by ANP in either age group. After TPTX, both net and fractional phosphate excretion decreased in both age groups. During PTH infusion in TPTX rats, both net and fractional phosphate excretions increased significantly in the adult rats but were unchanged in the weanling rats. In rats of the same age, the renal concentrating capacity and urinary excretion of prostaglandin E2 (PGE2) were determined after dehydration. The renal concentrating capacity was lower, and the renal excretion of PGE2 was higher, in the weanling than in the adult rats. Furthermore, the concentrating mechanism seems not to be influenced by indomethacin treatment in either age group. It is concluded that the tubular responses to ANP and PTH are blunted in the immature kidney and that the renal excretion of PGE2 is not an important factor in the regulation of the concentrating capacity in the weanling rat.     

Redistribution of glomerular filtration and renal plasma flow in CNS-induced natriuresis

Infusion of hypertonic sodium chloride solution into the third cerebral ventricle results in a marked increase in renal sodium output, indicating an important regulator of extracellular volume homeostasis. The intrarenal events governing the enhanced excretion have not been thoroughly studied previously. In 12 anaesthetized male rats a stainless steel cannula was introduced stereotaxically into the right lateral cerebral ventricle. Urine volume and excretion rates, Na, K, and osmotically active particles were measured during control infusion of artificial cerebrospinal fluid and during stimulation of central mechanisms with I M NaCl (520 nl min-1). At the end of the stimulation period, regional renal plasma flow (86RbCl) and glomerular filtration rate (51Cr-EDTA) were measured with single injection techniques. A second group of 12 non-stimulated rats served as controls. During ICV stimulation, the urine flow rate increased from 1.8 +/- 0.19 to 6.4 +/- 1.01 microliter min-1 (P less than 0.001). The urinary concentrations of Na and K increased, leading to a rise in the excretion rates of these ions from 0.12 +/- 0.025 to 0.96 +/- 0.352 mumol min-1 (P less than 0.001) and 0.40 +/- 0.083 to 1.70 +/- 0.196 (P less than 0.001), respectively. The osmolar excretion rate was 2.9 +/- 0.35 mu Osm min-1 before stimulation and 9.6 +/- 1.09 higher (P less than 0.001) during stimulation. Simultaneously the inner medullary plasma flow rose two-fold from 0.7 +/- 0.06 to 1.4 +/- 0.12 microliter min-1 tissue (P less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)     

Skeletal muscle and cardiac changes with training in patients with angina pectoris

Cardiovascular and skeletal muscle adaptations were studied before and after 6 mo of physical training in patients with coronary artery disease and exertional angina pectoris. Symptom-limited exercise capacity increased by 41% (470 +/- 30 to 665 +/- 35 kg.m.min-1; n = 29, P less than 0.001) with training as did skeletal muscle succinate dehydrogenase activity (1.75 +/- 0.24 to 3.31 +/- 0.24 IU; n = 23, P less than 0.001) and the areas of muscle fibers (type I from 43.6 +/- 3.3 to 54.4 +/- 3.3 micrometers 2 X 10(2); n = 21, P less than 0.05 and type II from 43.9 +/- 2.4 to 57.2 +/- 5.1 micrometers 2 X 10(2); P less than 0.01). At the same submaximal exercise intensity (mean 355 +/- 100 km.m.min-1), plasma catecholamines (1.31 +/- 0.14 to 1.07 +/- 0.09 ng.ml-1; n = 13, P less than 0.05), heart rate (115 +/- 3 to 97 +/- 3 beats/min; n = 29, P less than 0.001), and systolic blood pressure (171 +/- 4 to 143 +2- 4 mmHg; n = 29, P less than 0.001) were significantly reduced after training. Maximal coronary sinus blood flow (192 +/- 10 to 208 +/- 9 ml.min-1; n = 29, P less than 0.05) and left ventricular oxygen consumption (23.2 +/- 1.5 to 25.8 +/- 1.6 ml.min-1; n = 24, P less than 0.05) were increased by 8 and 11%, respectively, after training. The improvement in exercise capacity with training in patients with exercise is secondary to a reduction in myocardial oxygen requirements during subangina levels of exercise and partly to a small increase in maximal myocardial oxygen consumption. The skeletal muscle adaptations with training were not related to other indices of training such as the reduced exercise heart rate or increased symptom-limited exercise capacity.     

Effect of atrial natriuretic factor on renal prostaglandin E2 release in the anaesthetized dog.

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E2 (PGE2). In the first group, intravenous infusion of ANF (50 ng min-1 kg-1 body wt) reduced basal PGE2 release from 4.4 +/- 0.8 pmol min-1 to 1.8 +/- 0.7 pmol min-1. In the second group, intrarenal infusion of an alpha 1-adrenoceptor agonist, phenylephrine (2.5-6.75 micrograms min-1), raised PGE2 release from 2.7 +/- 0.5 pmol min-1 to 7.5 +/- 1.3 pmol min-1. During continuous alpha 1-adrenergic stimulation, intravenous infusion of ANF (100 ng min-1 kg-1 body wt) reduced PGE2 release to 3.5 +/- 1.0 pmol min-1. These results demonstrate that ANF reduces basal and alpha 1-adrenergic stimulated renal PGE2 release.     

Renal response to parathyroid hormone in the weanling rat

The renal response to parathyroid hormone and the activity of alkaline phosphatase in kidney cortex were studied in weanling and adult rats. Clearance studies for the determination of glomerular filtration rate and phosphate excretion were started 2 h after sham operation or thyroparathyroidectomy in 24- or 40-day-old rats. Urine was collected under basal conditions and following infusions with 0.5 and 1.0 mumol phosphate per 100 g body wt min-1. For enzyme studies, rats aged 14-40 days were used, and the activity of alkaline phosphatase in renal cortical slices was determined. Glomerular filtration rate was not influenced by thyroparathyroidectomy or phosphate infusions. Plasma phosphate increased during phosphate infusions and was significantly higher in thyroparathyroidectomized rats in all clearance periods. Both the net and the fractional excretions of phosphate were higher in intact than in thyroparathyroidectomized rats and the phosphate-retaining effect of thyroparathyroidectomy was similar in weanling and adult rats. Alkaline phosphatase activity in renal cortical slices increased between days 14 and 24 (1400-3190 IU mg-1 protein, P less than 0.01). During later development, no significant change was seen. It is concluded that the immature kidney of the weanling rats shows a parathyroid hormone-dependent adaptation to acute phosphate loading, and that changes in alkaline phosphatase activity are consistent with a maturation of this system only during early development.     

Effect of acute acidosis and alkalosis on leucine kinetics in man.

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.     

Renal effects of atriopeptin II and dopamine receptor blockade in acutely volume-expanded rats

Studies were made of the effects of continuous intravenous infusion of a synthetic atrial natriuretic factor (ANF) or, pre-treatment with the dopamine receptor antagonist haloperidol, on the renal response in anaesthetized rats subjected to volume expansion with an isotonic solution at 2% kg-1 body weight (wt) h-1. A time-control group receiving vehicle alone was studied in parallel. Measurements were compared 75 and 145 min after initiation of the volume expansion. Seventy minutes of Atriopeptin II infusion at 10 micrograms h-1 kg-1 body wt did not significantly alter the glomerular filtration rate [control value 1.29 +/- 0.10 ml min-1 g-1 kidney wt (n = 7, mean +/- 1 SEM), experimental value 1.20 +/- 0.12], but increased sodium excretion by 49% (from 2.87 +/- 0.56 to 4.27 +/- 0.45 mumol min-1). The arterial blood pressure was reduced by 9%. In previous investigations we found that in the same dosage Atriopeptin II increased sodium excretion 10-fold in euvolaemic animals. In the time-control group (n = 7) the response was similar to that in the atrial natriuretic factor-treated animals with the exception that the blood pressure was unaltered. Thus, glomerular filtration rate showed no statistically significant change (1.28 +/- 0.06 vs. 1.27 +/- 0.09 ml min-1 g-1 kidney wt) while the sodium excretion increased by 96% (from 2.29 +/- 0.22 to 4.50 +/- 0.49 mumol min-1). In animals pretreated with haloperidol (n = 5), the natriuretic response to the volume expansion was attenuated and was about ten times below that in the time-control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of verapamil on renin and aldosterone in the dog and rat

The purpose of this study was to evaluate the effects of calcium channel blockade on renin secretion and plasma aldosterone. Verapamil infusion (0.004 mg X kg-1 X min-1) into the renal artery of uninephrectomized dogs with an intact kidney resulted in significant increases (P less than 0.05) in renal blood flow, creatinine clearance, and the excreted fractions of Na+ and Cl-; renin secretion decreased (P less than 0.05) and plasma aldosterone did not change. Conversely, renal arterial infusion of verapamil in dogs with nonfiltering, denervated, papaverine-treated kidneys resulted in no change in renal blood flow and a significant increase (P less than 0.05) in renin secretion. In the rat, compared with untreated control animals, dietary verapamil (12.5 mg X kg-1 X day-1) did not effect plasma renin activity but significantly suppressed plasma aldosterone (P less than 0.001) in animals on NaCl-restricted [14.7 +/- 5.4 vs. 41.6 +/- 7.8 ng/dl (SE)] and NaCl-free [103.7 +/- 7.5 vs. 156.7 +/- 18.7 ng/dl (SE)] diets. In addition, verapamil suppressed (P less than 0.0003) plasma corticosterone [16.1 +/- 5.4 vs. 52.8 +/- 7.1 microgram/dl (SE)]. Thus, acute but not chronic verapamil administration stimulates renin release in the nonfiltering kidney, and chronic verapamil inhibits adrenal mineralocorticoid and glucocorticoid secretion. The disparate effects of verapamil on renin secretion from intact and nonfiltering kidneys may be due to actions of the Ca2+ channel blocker on renal hemodynamic and/or renal tubular mechanisms in the intact kidney that mask a direct effect of verapamil on renin-secreting cells.     

Haemodynamic and neurohumoral effects of cold pressor test in severe heart failure.

The effect of a cold pressor test (CPT) on haemodynamics in relation to general and regional sympathetic activity and arginin vasopressin (AVP), was studied in eleven patients with severe congestive heart failure (CHF). Compared to an age-matched control group (C), resting arterial plasma noradrenaline (NA) (419 +/- 77 vs. 182 +/- 15 pg ml-1), and adrenaline (A) (142 +/- 28 vs 54 +/- 10 pg ml-1) were higher (P less than 0.05) in CHF. AVP showed no significant difference (14 +/- 4 vs. 9 +/- 4 pg ml-1). During CPT systolic and diastolic blood pressure and systemic vascular resistance increased (P less than 0.01), as did NA (delta 114 +/- 39 pg ml-1, P less than 0.01), A (delta 33 +/- 10 pg ml-1, P less than 0.01) and heart rate (delta 10 beats min-1, P less than 0.01). The myocardial v-a difference of NA decreased (P less than 0.05), but was unchanged across the renal vascular bed during CPT. The a-v difference of NA in the hepatic vascular bed, and fractional extraction of A in the coronary sinus, renal and hepatic vascular beds remained unchanged during CPT. AVP did not change significantly and no change in cardiac index or left ventricular filling pressure was observed during CPT. These data suggest that despite an increased activation of the sympathetic nervous system at rest, a further increase in blood pressure and catecholamines took place during CPT. Thus, the effect of a CPT which activates the central sympathetic system seems not to be altered in patients with severe CHF.     

Determination of glomerular permselectivity to neutral dextrans in the dog

The multiple-indicator-dilution (MID) technique was used to separate solute flux (Js) across the glomerular and postglomerular capillaries in vivo. Anesthetized mongrel dogs (n = 20) during mannitol diuresis received a pulse of extracellular indicators including 125I-albumin (plasma reference), [14C]inulin (glomerular reference), creatinine (interstitial reference), and a neutral [3H]dextran (specific mol wt between 10,000 and 24,000 dalton) in the left renal artery. Left renal venous and ureteric outflows were rapidly sampled. 3H-labeled dextrans 10,000-15,500 had renal vein mean transit times (t) greater than those of 125I-albumin, indicating postglomerular extraction. 3H-labeled dextrans greater than 15,500 had t values identical to those of 125I-albumin, indicating only unidirectional glomerular extraction. The glomerular fractional dextran extractions relative to simultaneously injected [14C]inulin (ED/Ei) were calculated from urine and renal vein outflow curves and ranged from 0.98 +/- 0.02 to 0.33 +/- 0.12 (SD) for mol wt 10,000 +/- 24,000. ED/Ei values were quantitatively identical to constant-infusion fractional clearances of the same dextrans. Renal plasma flow (RPF) was then deliberately reduced two-to threefold in the same dog. ED/Ei as measured by the MID technique remained unchanged during graded reduction in RPF. In constant-infusion experiments RPF was reduced from 5.78 to 2.77 ml X s-1 X 100 g-1 and GFR from 50.4 to 36.3 ml X min-1, but the fractional neutral dextran clearances remained constant. The predominance of convective solute flux across the dog glomerulus permitted calculation of glomerular reflection coefficients 0.03 +/- 0.06 to 0.85 +/- 0.03 (SD) for neutral 3H-labeled dextrans 10,000-24,000 dalton.