Atrial natriuretic factor,urinary catechol compounds and electrolyte excretion in rats during normal hydration and isotonic volume expansion. Influence of dopamine receptor blockade.

To investigate the influence of acute isotonic volume expansion (VE) on the plasma concentration of atrial natriuretic factor (ANF), the excretion of catechol compounds and electrolytes and the whole kidney glomerular filtration rate (GFR), these variables were measured before and during 60 min of VE (2% of body weight per hour). Atrial natriuretic factor was measured at the end of the experiment. In a control group (n= 7) without volume expansion, plasma ANF was 58 ± 4 pg ml^-1. The excretion of sodium, dopamine (DA), 3 ,4–dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA) and GFR did not change during the control study. In VE animals (n= 7) plasma ANF was 82 ± 7pg ml^-1, significantly higher than in the control group. Sodium excretion increased more than 17–fold. The excretion of the DA increased by 38% and that of DOPAC by 30%. Noradrenaline excretion remained unchanged while GFR increased by 20%. In haloperidol-pretreated animals subjected to VE (n = 7). plasma ANF was 81± 8 pg ml^-1 during VE, significantly higher than in the control animals. Although the sodium excretion increased more than ninefold in this group during VE, this increase was only 55 % of that in the VE group not given haloperidol. The DA and DOPAC excretion was increased by haloperidol, indicating a feedback effect of receptor blockade. DOPAC excretion was not increased further by VE, hut the excretion of DA increased by 15% and GFR increased by 19%. In conclusion, haloperidol reduced the natriuretic response to VE without impairing either the VE-induced release of ANF or the increase in GFR. The results indicate an important involvement of ANF and DA in the natriuretic response to VE.     

Cardiac output and renal excretion rates during acute blood volume expansion in rats

Selected central vascular parameters and renal excretion rates were monitored in anesthetized rats after acute, isohemic blood volume expansion by 33 percent. The infusate was an equilibrated mixture of animals' own blood and isotonic, isoncotic (6 percent) bovine albumin. Expansion increased mean arterial pressure by 35 percent, mean central venous pressure (CVP) by 850 percent, cardiac output (CO) by 56 percent, hematocrit (Hct) by 25 percent, plasma protein concentration (Ppr) by 25 percent, renal excretion rates of volume by 4,400 percent, of sodium by 2,800 percent, and of potassium by 360 percent of the respective preinfusion value. Hct and Ppr measurements suggested that 15 min after the end of the infusion, only 33 percent of infused volume remained within the circulation and that there was little further change in this during the remainder of the experiment. At the end of the elevated renal response, CVP and CO alone had returned to control values. Renal excretion rates were highly correlated with CO, but they were delayed by 2-5 min with respect to it. The results suggest that the renal response to acute volume expansion does not primarily control blood volume. Cardiac output may be the controlled variable in the response.     

Influence of volume expansion,serum sodium,and fractional excretion of sodium on urate excretion

The relative contributions of volume expansion and increased fractional excretion of sodium to the uricosuria of saline infusion were assessed in 19 subjects by volume expansion with rapid infusion of 21 of hypertonic saline (3%), isotonic saline (0.9%), or hypotonic saline (0.45%). Urate excretion increased 385 mug/min (P less than 0.01) with hypertonic, 145 mug/min (P less than 0.05) with isotonic saline, and 294 mug/min (P less than 0.001) with hyptonic saline. When 150 meq of sodium chloride was administered as appropriate volumes of hypertonic, isotonic of hypotonic saline, the magnitude or uricosuria was correlated with volume load (r = 0.66, P less than 0.002). fractional excretion of sodium correlated with infusion volumes for all studies taken together (r = 0.35, P greater than 0.1). The relationship between fractional excretion of sodium and fractional excretion of urate was entirely attributed to their correlation with infusion volume. Both post-pyrazinamide urate excretion and pyrazinamide suppressible urate excretion increased with volume expansion.     

The release mechanism for atrial natriuretic factor during blood volume expansion and tachycardia in dogs

Atrial natriuretic factor (ANF) is released during blood volume expansion and tachycardia, but only blood volume expansion causes atrial distension, which presumably promotes ANF release. Our study was undertaken to search for a common release mechanism. In five anaesthetized, closed-chest dogs, plasma immunoreactive (IR) ANF was measured at three levels of blood volume, which were obtained by infusing a Ringer's solution. At each level of blood volume, plasma IR-ANF was measured at three pacing frequencies. Plasma IR-ANF increased as mean right atrial pressure (mRAP) was raised from 2 to 10 mmHg by volume expansion, whereas pacing tachycardia (at heart rates (HR) 50 +/- 3 and 98 +/- 1 beats min-1 above control) at each level of blood volume expansion increased plasma IR-ANF and systolic RAP (sRAP) at constant mRAP. Plasma IR-ANF was more strongly correlated to sRAP (r = 0.83) than to mRAP (r = 0.69), but the product sRAP x HR had the highest correlation coefficient (r = 0.86). According to the multiple regression equation: plasma IR-ANF = k1 + k2mRAP + k3sRAP + k4sRAP x HR, the product sRAP x HR had the highest coefficient of determination (r2 = 0.75) and was the only significant determinant. We conclude that atrial tension or stress, developing during each atrial systole, is an important determinant of ANF release. Since atrial diastolic and systolic dimensions do not increase during pacing tachycardia, ANF release is not dependent on atrial distension.     

CNS-induced natriuresis during dopamine receptor blockade. Further support for the existence of, at least, two separate natriuretic hormonal systems

Intracerebroventricular (ICV) stimulation with hypertonic sodium chloride solutions has previously shown indications to stimulate the release of a blood-borne natriuretic factor. Sodium excretion in this situation increases in the order of 10-20 times. Acute isotonic volume expansion has shown to be a potent stimulus for endogenous release of the atrial natriuretic factor (ANF). It has also been demonstrated that the natriuretic response to both volume expansion and exogenously applied ANF can be attenuated by the dopamine receptor blocker haloperidol. The present study was performed to investigate if the natriuretic response to ICV stimulation also could be attenuated with haloperidol, thus indicating similar effector mechanisms as for ANF. A first group of anaesthetized animals was, therefore, pre-treated with haloperidol (H) and then ICV stimulated (H-ICV). A second group of animals was subjected to acute isotonic volume expansion (VE, 2% b.w.h.-1) to evoke the documented ANF release. In a third group of animals pre-treatment with haloperidol was followed by volume expansion (H-VE). In the H-ICV group there was a more than 30-fold increase in sodium excretion, due to an increase both in urine flow rate (more than sixfold) and in the urinary concentration of sodium (more than fourfold). Potassium excretion increased more than eightfold, urine osmolality was unchanged, and blood pressure increased by 7%. In the VE group sodium excretion increased more than 18-fold, consequent to large increases in urine flow rate (more than 23-fold), while the urinary concentration of sodium tended to decrease. Potassium excretion increased more than threefold, urine osmolality decreased by 88%, and blood pressure was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats.

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.     

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 calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg^-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.     

Dopamine receptor blockade and synthesis inhibition during exaggerated natriuresis in spontaneously hypertensive rats.

The influence of dopamine receptor blockade and synthesis inhibition on natriuresis induced by isotonic saline volume expansion was investigated in anaesthetized spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The aim of the study was to elucidate the mechanisms underlying the phenomenon of exaggerated natriuresis during volume expansion that has been observed in spontaneously hypertensive rats. Volume expansion, at 5% of body weight, resulted in a larger and faster natriuretic response in spontaneously hypertensive rats than in Wistar-Kyoto rats. Sixty minutes after commencement of volume expansion the natriuretic response (accumulated sodium excretion) in Wistar-Kyoto rats (n = 8) was only 24% of that in spontaneously hypertensive rats (n = 17). When spontaneously hypertensive rats were pretreated with the dopamine receptor blockers haloperidol (n = 14, 1 mg kg-1), SCH23390 (n = 8, 30 micrograms h-1 kg-1) or the dopamine synthesis inhibitor benserazide (n = 8, 50 mg kg-1; n = 5, 100 mg kg-1), the natriuretic response to volume expansion was only 16, 35, 59 and 42%, respectively, of that in untreated SHR. The corresponding proportion in the haloperidol-treated (n = 8) compared with untreated Wistar-Kyoto rats was 22%. In conclusion, isotonic volume loading results in more pronounced natriuresis in spontaneously hypertensive than in Wistar-Kyoto rats. Dopamine receptor blockade and synthesis inhibition attenuate the expansion of exaggerated natriuresis in spontaneously hypertensive rats and reduces the volume expansion natriuresis in Wistar-Kyoto rats, indicating that the dopamine system plays an important role.     

Atrial natriuretic peptide, renin activity, aldosterone, urine volume and electrolytes during a 24-h sleep-wake cycle in man

To investigate the diurnal variation in the plasma atrial natriuretic peptide (ANP) concentrations and its relation to renin activity, aldosterone, urine volume and electrolytes, blood samples from six healthy male subjects were collected and blood pressure and heart rate recorded every 4 h during a 24-h sleep-wake period. Systolic blood pressure and heart rate were at the lowest during sleep. Plasma ANP, extracted on Sep-Pak cartridges and measured by radioimmunoassay, had the highest concentration at midnight and lowest at 04.00 h (27 +/- 18 vs 16 +/- 18 ng l-1, mean +/- SD, P less than 0.05 after normalization of the original values). Plasma renin activity and aldosterone were at the highest at 08.00 and 12.00 h, whereafter they both began to decrease (P less than 0.001, also normalized). Urinary volume, sodium, potassium and chloride showed highest values (P less than 0.05) between 08.00 and 16.00 h. Plasma ANP levels did not correlate with systolic blood pressure, heart rate, serum or urinary Na or plasma renin or aldosterone (r = 0.1-0.3, P greater than 0.05). Plasma renin activity correlated with aldosterone and aldosterone with urinary K (r = 0.66 and 0.58 respectively, P less than 0.001). These results suggest that the low plasma ANP levels found in our subjects at 04.00 h may be associated to diminished atrial distension accompanied by the inactivity of the sleep period. In addition, ANP does not appear to affect the secretion of renin and aldosterone in a normal sleep-wake cycle.     

Reduced urinary noradrenaline excretion during rest, exercise and cold stress in trained rats: a comparison between physically-trained rats, cold-acclimated rats and warm-acclimated rats.

Physically trained rats were compared with cold-acclimated rats. Trained as well as cold-acclimated rats showed cardiac and adrenal hypertrophy. Cardiac noradrenaline (NA) content was increased in both groups of rats but only the trained rats had an increased cardiac NA concentration. The adrenal NA content was increased in both groups but only the trained rats had an increased adrenal content of adrenaline (A). The spleen of trained rats had an increased NA content, while that of cold-acclimated rats had a decreased NA content. The submandibular glands of cold-acclimated rats were enlarged and had an increased NA content. Trained as well as cold-acclimated rats had lower urinary NA excretions during rest, after exercise and during cold stress when compared with controls. However, only the trained rats had a reduced net increment in NA excretion after exercise, whereas there was no difference between the increments of cold-acclimated and control rats. Six months after cessation of training, ex-trained rats still had an increased heart ratio and a reduced urinary NA excretion after exercise. It is suggested that physical training induces "cross tolerance" to cold stress, while cold-acclimation does not lead to "cross tolerance" to acute exercise.     

Influence of circadian time, ageing, and hypertension on the urinary excretion of nitric oxide metabolites in rats

Urinary excretion of NO metabolites (NOx) was measured in male spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) in two age groups: young (11 weeks) and old (58 weeks). Urine was collected every 6 h throughout 24 h with and without injection interperitoneally of N(G)-nitro-L-arginine-methyl-ester (L-NAME), 30 mg/kg, at 7:00 or 19:00 h. In addition, blood pressure changes by L-NAME were evaluated using radiotelemetry. In both strains of rats, injection of L-NAME abolished almost completely the urinary excretion of NOx, indicating that urinary NOx indeed reflect the endogenous rate of NO synthesis. Time-dependent variation in urinary NOx excretion was observed in WKY rats of both ages (analysis of variance, P<0.05), with higher excretion in the dark period. In SHR rats, time-dependent variation in NOx excretion was lost, and the overall amount of NOx excreted within 24 h was significantly lower in young SHR than in age-matched WKY rats. Moreover, blood pressure increases by L-NAME were significantly smaller in SHR than in WKY rats. In old rats of both strains, NOx excretion was reduced, and the difference between the strains disappeared. Our findings demonstrate that ageing is accompanied by a loss in NOx excretion, and suggest that hypertension in SHR leads to a reduction in NO synthesis already at young age.     

Efferent renal nerve activity during intracarotid and intracerebroventricular infusions of hypertonic sodium chloride solutions and isotonic volume expansion in the rat

The change in renal nerve activity under conditions known to increase renal sodium excretion was studied. In adult Sprague Dawley rats, anaesthetized with Inactin®, nor-motonic and hypertonic NaCl solutions were infused into 1) a vein, 2) a carotid artery and 3) the third ventricle. The left kidney was freed and placed in a plastic cup. A renal nerve was dissected free and placed on a stainless bipolar electrode. The nerve was cut distal to the electrode. The nerve signals were amplified and recorded on a tape recorder. Simultaneously integrated nerve signals and also arterial and venous pressures were recorded. Intracarotid infusion of a 1 M NaCl solution increased sodium output and temporarily decreased renal nerve activitv by some 35%. Corresponding intravenous (i.v.) infusion gave an increase in renal nerve activity and also in sodium output. The latter increase was delayed compared with that caused by the intracarotid infusion. No variations in blood pressure were noted. In control experiments with a slow i.v. infusion of physiological saline, renal nerve activity increased throughout the experiment, while sodium excretion remained constant. During infusion of a 1 M NaCl solution into the third ventricle, renal nerve activity decreased in about half of the cases. This reduction was often accompanied by an increased arterial blood pressure and an increased sodium output. Arterial blood pressure increases were especially pronounced at the highest infusion rate, i.e. 800 nl-min-¹. Isotonic volume expansion of 2% of the body weight resulted in a transient decrease in renal nerve activity by about 30%. Venous blood pressure rose and sodium output increased six-fold. The decrease in nerve activity was observed both when the vagal nerves were intact and when they were cut.     

一肾一夹和两肾一夹高血压和血压逆转大鼠血浆、心房和心室心钠素水平的变化特征

利用一肾一夹容量型和两肾一夹压力型大鼠肾血管性高血压所敛心肌肥厚及高血压逆转肥厚逆转模型,测定血浆、心房和心审心钠素水平。发现两型高血压大鼠血浆及左室的心钠素水平明显增高,左室及血浆心钠素浓度与相对室重呈正相关,左房心钠素浓度在一肾一夹型明显降低;随着高血压的逆转,两型大鼠血浆及心房心钠素水平基本恢复,增高了的心室心钠素由高水平下降。结果提示。在高血压、容量扩张并伴有心肌肥厚的病理情况下,心室心钠素可能起重要的代偿调节作用。     

Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during moderate anti-diuresis.

The hypothesis that potassium depletion (KD) might play a role in stimulating the renal synthesis of prostanoids, and that these materials can contribute to hypokalaemic renal dysfunction, has been tested. Healthy women were studied either in normal potassium balance (N,n = 14), or in experimental KD. KD was induced by low dietary potassium intake (less than or equal to 10 mmol day-1) and natriuretic treatment, associated with replacement of net NaCl and water loss. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 +/- 43 mmol (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary PGE2, 6-keto-PGF1 alpha, TxB2 concentrations by the RIA method were measured during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by the infusion of low-dose lysine-8-vasopressin (LVP). Compared to the N group, only in the KD2 group do glomerular and tubular dysfunctions typical of hypokalaemia and reduced prostanoid excretions (significant for 6-keto-PGF1 alpha and TxB2 but not for PGE2) appear during polyuria besides the significant reductions of plasma potassium concentration, urinary potassium excretion and the significant increase in plasma renin activity. During LVP infusion the urinary prostanoid excretions were all significantly lower in absence of significant differences in urinary flow rate. Concerning its renal effects, LVP lost its ability to reduce the creatinine cl., while expressing a trend towards reduction in fractional chloride excretion. Indomethacin pretreatment restored the LVP effect on creatinine cl. and increased the antichloruretic LVP effect (although not significantly). To the extent that urinary prostanoid excretions reflect their intrarenal synthesis, our data demonstrate that KD inhibits this biosynthesis. A depressed production of prostanoids endowed with vasodilating and chloruretic activity probably played a role in attenuating the renal vascular hyporeactivity and the urinary chloride dispersion induced by KD.     

Circadian rhythms and the urinary excretion of acid glycosaminoglycans in normal human adults.

Urine from normal human adults (11 males, 4 females) was collected for 24 hours in four-hour samples, commencing at 08.00 hours. The urine volume, and concentrations of chondroitin sulfate, heparan sulfate, cetylpyridinium turbidity, and creatinine were measured on every sample. Concentrations and total output of glycosaminoglycans were significantly higher in male urine than in female urine. Chondroitin sulfate total output/four hours showed a significant negative correlation with creatinine concentration in males, but not in females. A testicular hyaluronidase is implicated. No such correlation was observed for heparan sulfate. Glycosaminoglycans are filtered into the urine. Plasma clearances are very low. Heparan sulfate is excreted with a circadian rhythm, as is glycosaminoglycan assayed by cetyl pyridinium turbidity. Peak excretions are at 06.00 and 10.00 hours respectively. Chondroitin sulfate excretion is not rhythmic in the male, perhaps because hyaluronidase activity in the urine complicates the assay. A rhythm may be present in the female.