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)     

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)     

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)     

CNS-induced natriuresis is not mediated by the atrial natriuretic factor

Studies were performed on anaesthetized Wistar-Kyoto rats to investigate whether the natriuretic response to stimulation of the cerebroventricular system with a hypertonic sodium solution is in part caused by increased plasma concentrations of atrial natriuretic factor (ANF). Through a cannula inserted into a lateral cerebral ventricle a solution with a normal (CSF, 152 mmol l-1) or high (NaCSF, 1,000 mmol l-1) sodium ion content was infused. In the stimulated animals which received NaCSF, the sodium excretion increased more than 13-fold, from 0.07 +/- 0.02 (mean +/- SEM) to 0.97 +/- 0.22 mumol min-1 g-1 kidney wt (P less than 0.01). Potassium excretion rose more than eight-fold, from 0.37 +/- 0.05 to 3.01 +/- 0.13 mumol min-1 g-1 kidney wt (P less than 0.001), and the urine flow rate more than seven-fold, from 1.35 +/- 0.11 to 9.74 +/- 1.23 microliters min-1 g-1 kidney wt (P less than 0.001). The mean arterial blood pressure increased from 100 +/- 3 to 129 +/- 7 mmHg (P less than 0.001). In the control animals which received CSF throughout the experiment there was no significant change in the above variables. The concentrations of ANF in plasma taken at the end of the experiments were determined by a radioimmunoassay. The mean plasma concentration of ANF in animals receiving CSF throughout the experiment was 175 +/- 36 pg ml-1. This was not significantly different from the corresponding value in animals which were given NaCSF (118 +/- 34 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase in plasma sodium enhances natriuresis in response to a sodium load unable to change plasma atrial peptide concentration

The influence of plasma sodium concentration in the control of sodium excretion was investigated in conscious, water-diuretic dogs. NaCl was infused for 60 min as a hypertonic or isotonic solution at a rate of 60 mumol NaCl min-1 kg-1 body wt. Plasma sodium concentration rose only during hypertonic infusion (P less than 0.05). Sodium excretion increased markedly with both infusions (hypertonic, from 2.4 +/- 0.6 to 105 +/- 27 mumol min-1; isotonic, from 3.9 +/- 1.3 to 58 +/- 17 mumol min-1). Fractional sodium excretion increased more during hypertonic than during isotonic infusion. Hypertonic infusion decreased diuresis from 3.1 +/- 0.5 to 1.3 +/- 0.6 ml min-1, while isotonic infusion elicited an increase from 3.9 +/- 0.5 to 7.2 +/- 0.7 ml min-1. Plasma renin activity and plasma aldosterone decreased markedly in both series (P less than 0.05), the relative changes in the two series being very similar. Central venous pressure increased (2.8 +/- 0.7 to 4.5 +/- 1.0 mmHg) during isotonic infusion but not significantly during hypertonic infusion. Arterial pressure, heart rate and plasma levels of atrial natriuretic peptide and catecholamines did not change measurably in either series. It is concluded that simultaneous increases in extracellular volume and sodium concentration cause a larger natriuretic response than a change in volume alone, and that a 40-fold increase in sodium excretion may occur without measurable changes in plasma atrial natriuretic peptide concentration.     

Renal response to captopril in conscious dogs pretreated with indomethacin

This study was designed to determine whether the prostaglandins mediate the renal effects of captopril in the conscious sodium-replete dog. In a group of control animals (n = 9), effective renal plasma flow (ERPF) increased from 185 +/- 15 to 230 +/- 12 ml/min and plasma renin activity (PRA) increased from 0.64 +/- 0.15 to 12.9 +/- 1.1 ng ANG I . ml-1 . h-1 after captopril (10 mg/kg bolus plus 10 micrograms . kg-1 . min-1 i.v.) administration. Glomerular filtration rate (GRF) and sodium excretion (UnaV) were also increased significantly following captopril treatment, whereas urine volume (V), potassium excretion (UkV), mean arterial pressure (MAP), and heart rate (HR) remained unchanged throughout the experiment. When the same dose of captopril was given to indomethacin-pretreated dogs (5 mg/kg bolus plus 2 micrograms . kg-1 . min-1 i.v.), ERPF increased from 170 +/- 8 to 265 +/- 18 ml/min and PRA increased from 1.2 +/- 0.4 to 14.6 +/- 3.0 ng ANG I . ml-1 . h-1 after the captopril, while UnaV, UkV, and V remained unchanged. These data demonstrate that the prostaglandins do not mediate the ability of captopril to increase PRA or effective renal plasma flow in this experimental model.     

Contribution of renal prostaglandins to the natriuretic action of bradykinin in the dog.

To study the effects of stimulation of renal prostaglandin biosynthesis by bradykinin, we assessed the changes in renal functions induced by intrarenal infusion of bradykinin (10 ng . min-1 . kg-1) in the dog anesthetized with pentobarbital before and during inhibition of prostaglandin synthesis by sodium meclofenamate (5 mg/kg). Before meclofenamate administration, bradykinin augmented the urinary output of a "PGE"-like substance from 1.00 +/- 0.25 to 3.88 +/- 1.09 ng/min (P less than 0.05) and increased renal blood flow by 65 +/- 9 ml/min (P less than 0.001), urine flow by 0.55 +/- 0.23 ml/min (P less than 0.05), and sodium excretion by 64.8 +/- 18.0 mueq/min (P less than 0.01). Administration of meclofenamate did not affect the bradykinin-induced increase in renal blood flow and urine volume, but suppressed the evoked output of "PGE" and reduced the associated natriuresis, i.e., sodium excretion increased by only 11.1 +/- 4.8 mueq/min (P greater than 0.05). In contrast, meclofenamate did not affect the natriuresis effected by an equidilator dose of PGE2 (5 ng . min-1 . kg-1) infused intrarenally. These observations suggest that a product of prostaglandin synthetase produced by the kidney during intrarenal infusion of bradykinin contributes to the natriuretic action of the peptide.     

C-type natriuretic peptide does not affect plasma and urinary adrenomedullin in man.

To investigate whether C-type natriuretic peptide (CNP) at pathophysiological plasma levels stimulates the release of adrenomedullin (ADM) in man, six healthy subjects (three men and three women, mean age 35 +/- 3 years, range 33-40 years) received an intravenous infusion of synthetic human CNP-22 (2 pmol kg-1 min for 2 h), in a single-blind, placebo-controlled, random order, cross-over study, with measurements of the plasma levels of cyclic guanosine monophosphate (cGMP), ADM, renin and atrial natriuretic peptide (ANP), arterial pressure, heart rate, renal blood flow (para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), and the urinary excretion rates of cGMP, ADM and sodium. Infusion of CNP induced increases in its own levels (from 1.17 +/- 0.11 up to 21.13 +/- 1.41 pmol l-1) without modifying the plasma levels of cGMP, ADM, renin and ANP, the urinary excretion rate of ADM and cGMP, renal haemodynamics and sodium excretion. These data indicate that circulating CNP is not involved in the regulation of ADM release, renal haemodynamics and sodium excretion in man.     

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.     

Exaggerated volume expansion natriuresis in rats preloaded with hypertonic saline: a paradoxical enhancement by inhibition of prostaglandin synthesis

In preliminary experiments rats preinfused with hypertonic saline showed exaggerated natriuresis after an additional small volume expansion (SVE). This was systematically studied in anaesthetized Wistar rats prepared for clearance studies of the left kidney and measurements of medullary blood flow (MBF, laser-Doppler technique) and tissue electrical admittance (Y ), an index of interstitial ion concentration. The rats were preinfused i.v. with 3 mL of 5% NaCl during 90 min. A subsequent injection of isotonic saline, 0.5% of body weight, increased sodium excretion (UNaV ) from 2.1 +/- 0.5 to 4.5 +/- 1.1 micromol min-1 and urine flow (V ) from 12.0 +/- 2.3 to 24.3 +/- 5.6 microL min-1 (P < 0.02). The same volume of whole blood increased UNaV from 5.0 +/- 1.4 to 8.7 +/- 1.7 micromol min-1 and V from 22.3 +/- 5.1 to 37.4 +/- 5.9 microL min-1 (P < 0.01). The glomerular filtration rate, MBF and Y did not change. In rats preinfused with 0.9% saline no natriuresis was observed after SVE. To examine if prostaglandins (PG) were involved in SVE natriuresis, indomethacin (Indo), 5 mg kg-1 or sodium meclophenamate (Meclo), 7.5 mg kg-1, were added to the injected 0.9% saline. Paradoxically, both PG synthesis inhibitors enhanced natriuresis to SVE. After Indo UNaV increased from 2.0 +/- 0.6 to 7.6 +/- 1.3 micromol min-1, significantly more than after SVE alone (P < 0.001). At higher baseline UNaV, the increase with Meclo from 4.5 +/- 1.2 to 13.5 +/- 1.8 micromol min-1 was significantly higher than after whole blood infusion (P < 0.001). MBF decreased and Y increased after both inhibitors. Further studies are required to explain the enhancement of natriuresis after blockade of PG synthesis.     

Effect of hypertonic intracarotid infusions on plasma vasopressin concentration

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intracarotid infusion (1.5 +/- 0.3 pg/ml), was increased (P less than 0.05) after hypertonic saline to 3.2 +/- 0.6 and 4.8 +/- 0.2 pg/ml for the 90 and 180 mumol . kg-1 . min-1 infusions, respectively. The cerebral osmolality indicated by jugular vein pOsm was therefore increased in the absence of changes in systemic pOsm during intracarotid hypertonic infusions. The increase in pAVP in response to these changes in pOsm supports the presence of central osmoreceptors regulating vasopressin release in the area of distribution of the common carotid arteries.     

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.     

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.     

Endogenous variations and sodium intake-dependent components of diurnal sodium excretion patterns in dogs.

1. Automated, sequential, 20 min urine collections were made to provide a record of diurnal variations of urinary sodium excretion (UNaV) in seven dogs, in which the same daily intake of sodium, potassium and water was administered, at first orally (between 08.30 and 08.50 h) on day 1 and then by i.v. infusion at a constant rate on days 2 and 3. This basic protocol was employed for two different levels of sodium intake: normal (NSI; 2.5 mmol (kg body wt)-1 (24 h)-1) and high (HSI; 14.5 mmol (kg body wt)-1 (24 h)-1). 2. The aims were: firstly, to establish the diurnal pattern of UNaV under these circumstances; secondly, to find out whether the quantity of sodium administered influences this diurnal pattern; and thirdly, to distinguish endogenous fluctuations from intake-dependent components in the UNaV excretion patterns. 3. On day 1 (oral intake) all dogs exhibited a similar excretion pattern, which peaked between 13.00 and 15.00 h on both diets and then diminished again over the remainder of the 24 h period. 4. On days 2 and 3 (infusion) UNaV fluctuated within a considerable range. 5. On HSI, the maximal UNaV rates on day 1 were about double those observed on infusion days. On HSI, UNaV during infusion days seems to consist of a constant basal component of about 5-6 mumol (kg body wt)-1 min-1 upon which a fluctuating component is superimposed. The basal component may be a reactive homeostatic response to the high sodium intake, whereas the superimposed fluctuating component may reflect endogenous variations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous opioids and electrolyte excretion after contralateral renal exclusion

Acute reductions in functioning renal mass result in increases in both sodium (U Na V) and potassium (U K V) excretion by the contralateral kidney (CK). We studied the role of endogenous opioids in this response. In control experiments acute unilateral nephrectomy (AUN) increased U Na V from 1,788 +/- 1,125 (SD) to 3,939 +/- 1,819 and U K V from 1,385 +/- 561 to 2,254 +/- 832 neq/min by the CK (P less than 0.005 for both); similar results occurred in rats undergoing acute unilateral ureteral occlusion (UUO). These increases occurred without overall change in GFR or mean arterial pressure. In rats receiving a continuous infusion of the opiate-receptor antagonist naloxone (0.3 mg . kg-1 . h-1) neither AUN nor UUO produced significant alterations in U Na V or U K V by the CK; naloxone infusion by itself did not alter GFR or basal rates of cation excretion. A separate group of rats was made tolerant to morphine by subcutaneous implantation of pellets containing 75 mg morphine base. In these rats, AUN also failed to produce any increase in U Na V or U K V by the CK. The results suggest that acute reductions in functioning renal mass produced by either AUN or UUO stimulate cation excretion by the remaining kidney through reflex pathways that involve opiate receptors.     

Adrenocorticoid regulation of Na+,K(+)-ATPase in adult rat kidney: effects on post-translational processing and mRNA abundance.

The mechanisms by which adreno-corticoid hormones regulate Na+,K(+)-ATPase in adult kidney were studied in adrenalectomized (Adx) rats. Five days after adrenalectomy, Na+,K(+)-ATPase activity was significantly reduced in the renal cortex homogenate (C = 13.0 +/- 0.8 vs. Adx = 7.1 +/- 0.7 mumol Pi mg-1 protein h-1) and in renal microsomes (C = 30.3 +/- 1.9 vs Adx = 14.6 +/- 1.3 mumol Pi mg-1 protein h-1). Glucocorticoid replacement treatment of adrenalectomized rats with betamethasone (20 micrograms kg-1 body wt twice daily for 5 days) effectively counteracted the observed reduction in Na+,K(+)-ATPase activity. In cortical homogenate the protein level of alpha 1 and beta 1 subunits measured in immunoblots was not significantly different in Adx and control rats, indicating that 5 days after adrenalectomy the alpha 1 and beta 1 subunits were present in renal cortical cells to almost normal extent but could not be assembled into a transmembrane functional unit. In support of this conclusion we found that the protein level of both the alpha 1 and beta 1 subunits was significantly lower (P less than 0.001 for both subunits) in microsomes from Adx than in control rats. The mRNA abundance for alpha 1 and beta 1 subunits were not lower in Adx as compared to control rats 1 and 5 days after surgery. However, if Adx rats were given a single dose of betamethasone (600 micrograms kg-1 body wt), a significant 2-fold increase in both alpha 1 and beta 1 mRNAs was observed (P less than 0.05 for both subunits).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal response to low and high phosphate intake in weanling, adolescent and adult rats

The renal response to low and high phosphate intake was studied in weanling, young and adult rats. Weanling rats were started on experimental diets containing 0.37%, 0.7%, or 1.7% phosphate at 24 days and adult rats at 60 days of age. After 21 days, clearance studies were done in anaesthetized animals. Urine was collected during basal conditions and following a phosphate infusion. Urinary excretion of calcium, phosphate and creatinine, and plasma levels of phosphate and creatinine were determined. Plasma phosphate was slightly higher in the younger rats in all dietary groups but was not influenced by phosphate intake in either age group. Urinary phosphate excretion and fractional phosphate excretion increased significantly in both age groups with increasing phosphate intake. After high phosphate intake, both net and fractional phosphate excretions were significantly higher in younger rats (0.97 +/- 0.08 and 0.24 +/- 0.06 mumol min-1 100 g-1, P less than 0.01, and 47.5 +/- 3.84 and 18.15 +/- 5.59%, P less than 0.01, respectively). The urinary excretion of calcium related to creatinine was higher in younger rats in all dietary groups with the highest value found after low phosphate intake. During an acute phosphate infusion, fractional phosphate excretion increased significantly in both age groups after normal phosphate intake but remained unchanged after low or high phosphate intake. Plasma phosphate increased significantly only in younger rats with high phosphate intake (2.9 +/- 0.18, 3.88 +/- 0.43, P less than 0.05). It is suggested that hypercalciuria reflects early stages of phosphate depletion and that in young rats stabilized on a high phosphate intake, phosphate retention may occur during an acute phosphate load.     

Effects, release and disposal of endothelin-1 in conscious dogs.

Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg-1 min-1) were investigated in conscious dogs. In addition, the disappearance of ET-1 in arterial and central venous plasma after an infusion of 10 ng kg-1 min-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg-1 min-1) and angiotensin II (AII, 2, 5, and 10 ng kg-1 min-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 +/- 0.3 to 243 +/- 23 pg ml-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 +/- 4 to 29 +/- 3 ml min-1 and 87 +/- 16 to 71 +/- 14 mumol min-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t1/2 was 1.1 +/- 0.1 min. Vasopressin increased arterial blood pressure (107 +/- 4 to 136 +/- 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin--in contrast to angiotensin II--is able to increase the plasma concentration of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal function in Lophius americanus: effects of angiotensin II.

Arterial blood pressure, urine flow rate, and plasma and urine electrolytes were measured in the aglomerular goosefish (L. americanus) before, during, and after the intravenous infusion of angiotensin II (from 5 to 280 ng/min.kg body wt). Increases in arterial blood pressure were directly related to the logarithm of the angiotensin infusion rate (r = 0.62, P less than 0.005). Angiotensin also increased urine flow from 0.676 +/- 0.065 to 0.755 +/- 0.068 ml/h.kg body wt (P less than 0.005) and Na excretion from 41.0 +/- 5.5 to 54.4 +/- 7.0 mumol/h.kg body wt (P less than 0.001). In 17 of the 19 fish infused with angiotensin the diuretic and natriuretic effects were directly related to the logarithm of the infusion rate (r = 0.44, P less than 0.04 and r = 0.51, P less than 0.02, respectively). There was no relationship between the pressor and the diuretic or natriuretic effects of angiotensin II. These results are consistent with inhibitory effects of angiotensin on solute transport by aglomerular tubules.     

The calcium entry blocker verapamil increases red cell flux in the vasa recta of the exposed renal papilla

To investigate the vasoreactivity of the vessels of the juxtamedullary vasculature, measurements were made of the red blood cell flux (Qrbc) in the vasa recta of the exposed renal papilla of anaesthetized rats by means of fluorescently labelled erythrocytes. The flux was measured before and after intravenous administration of the calcium entry blocker verapamil, which was infused in two different doses. A control group receiving vehicle was studied in parallel. The lower dose of verapamil (0.6 mg h-1 kg-1 body wt) increased Qrbc by 30 +/- 6% (n = 9, P less than 0.05, mean +/- 1 SEM) and reduced the systemic blood pressure by 6% (P less than 0.05). The osmolality of urine samples from the papillary tip remained statistically unchanged (1199 +/- 60 vs. 1186 +/- 102 mosM kg-1 H2O). In the animals receiving the higher dose of verapamil (2.4 mg h-1 kg-1 body wt), Qrbc increased by 39 +/- 7% (n = 10, P less than 0.05) and the blood pressure was reduced by 9% (P less than 0.05), while urine osmolality was unchanged (1104 +/- 110 vs. 1264 +/- 123 mosM kg-1 H2O). In the time control group there was no statistically significant change in Qrbc (+6 +/- 8%, n = 10), blood pressure or urine osmolality (1006 +/- 61 vs. 1091 +/- 70 mosM kg-1 H2O). The verapamil-induced increase in Qrbc is probably mainly mediated by a relaxation of the afferent arteriole of the juxtamedullary nephrons. The results confirm our previous indication of a high vasoreactivity in the vessels of the juxtamedullary vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)