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Effect of indomethacin on modest pressure natriuresis in chloralose-anesthetized, non-laparotomized dogs.

To determine if indomethacin (indo) would attenuate the effects of changed renal perfusion pressure on sodium excretion as reported by others, we performed clearance studies in chloralose-anesthetized dogs without the major stress of laparotomy. Mean renal arterial pressure was varied by a balloon-tipped catheter indwelling the aorta suprarenally. With pressure decreases to mean values above 85 mm Hg during isotonic saline infusion, sodium output decreased only by 10.7 +/- 2.4% per 10 mm Hg pressure decrease without indo pre-treatment but decreased by 22.0 +/- 3.8% per 10 mm Hg pressure decrease with indo pre-treatment. The greater, rather than lesser, pressure effect on excretory function after indo in these experiments with chloralose anesthesia suggest that renal prostaglandin (PG) activity does not mediate normally pressure natriuresis. Instead, the data suggest that, in the absence of major stress, the renal pressure effects on excretory function may become more sensitive after indo. In addition, we postulate that the normal acute pressure natriuresis may be modest and may average no more than 20% change for each 10 mm Hg change in mean pressure above 90 mm Hg when stress is minimal and when vasoactive preglomerular autoregulation is nearly perfect. This is a phenomenon which keeps intrarenal tissue pressure and urine output relatively constant with arterial pressure elevations.

Anesthesia↗

The mechanism of polyethylene glycol-induced natriuresis in rats: role of atrial natriuretic hormone.

A putative role of atrial natriuretic hormone (ANH) in a polyethylene glycol (PEG) 200-induced natriuresis was examined in conscious Wistar rats. Low molecular weight PEG 200 (0.5 or 1.0 ml/100g body weight) was orally administered to rats by gavage. Urine was collected during a 3 hr test period and blood was obtained at the end of each experiment for measurement of ANH, PRA, clearance studies and for indirect indices of plasma volume. Urinary excretion of sodium and volume increased while plasma ANH concentrations were markedly decreased in a dose-related manner following PEG 200 administration. The osmotic clearance was also elevated following PEG 200 administration. No significant change was observed in any of the parameters following high molecular weight PEG 8000. The observed decrease in ANH was associated with an apparent contraction of plasma volume despite the increased serum osmolality. These data indicate that the ANH inhibitory influence of the decreased plasma volume takes precedence over the stimulatory effect of the hyperosmolality and the latter is primarily responsible for the increased osmotic clearance and natriuresis observed in this model.

Administration, Oral↗

The effect of prostaglandin inhibition on the natriuresis of drug-induced renal vasodilatation.

It has been suggested that increased prostaglandin release may mediate the natriuresis seen during the administration of renal vasodilators. To further investigate this possibility, either acetylcholine (40 microgram/min) or bradykinin (5 microgram/min) was infused into the left renal artery of anesthetized dogs previously given an inhibitor of prostaglandin synthesis. During the infusion of either vasodilator drug in the prostaglandin-inhibited dogs, urinary sodium excretion increased to a similar degree as in a group of normal dogs with intact prostaglandin synthesis. These studies therefore do not confirm that prostaglandins play a significant role in the natriuresis of drug-induced vasodilatation.

Acetylcholine↗

Natriuresis, kaliuresis and diuresis in the rat following microinjections of carbachol into the septal area.

The effects of intraseptal injection of carbachol on natriuresis, kaliuresis and diuresis has been studied in conscious, unrestrained water-loaded male rats. Urinary sodium and potassium excretion increased following injections into the septal area. The intensity of the natriuresis and kaliuresis was dose-related. An antidiuretic effect was also observed. The Na+/K/ ratio increased with increasing doses of carbachol, indicating that the rise in urinary sodium exceeded that of potassium. Systematic mapping of the septal area yielded about the same results for all sites, excepting a zone located in the anterior-dorsal part of the medial nucleus which appeared more sensitive. The natriuretic effect of intraseptal carbachol in adrenalectomized rats demonstrated the secondary role played by the adrenals. Contrariwise the decrease of the natriuretic effect observed either in hypophysectomized rats or in rats bearing a median eminence lesion receiving intraseptal carbachol showed the important participation of these structures in urinary Na+ excretion. Adrenalectomy or median eminence lesions did not modify the kaliuretic response while hypophysectomy produced a transitory diminution. This fact favours the hypothesis of different mechanisms involved in Na+ and K+ excretion following intraseptal carbachol. These results leave open the question as to mechanism of action but suggest a possible role of the pituitary in mediating the responses. Also, the possibility of a role played by hemodynamic shifts is suggested.

Adrenal Glands↗

Natriuresis, not seizures, induced by cholinergic stimulation of the locus coeruleus is affected by forebrain lesions and water deprivation.

Two groups of rats with electrolytic lesions of the medial and upper septal area (MUL) or, alternatively, of the anteroventral portion of the third ventricle (AV3V) and a third group of sham-operated rats were water loaded and received three carbachol injections into the locus coeruleus according to the following schedule: 1) prelesion, 2) on the second postlesion day and 3) on the seventh postlesion day. Both MUL and AV3V lesions inhibited the carbachol-induced natriuresis on the second postlesion day. Recovery was almost complete after MUL but not after AV3V lesion on the seventh day. Water deprivation also reduced the carbachol-induced natriuresis but passive hydration of AV3V animals did not avoid the impairment induced by the lesion. Transient seizure phenomena such as clonic convulsions, salivation and analgesia subsequent to carbachol injection were not altered by the lesions.

Animals↗

Relationship of body composition to stress-induced pressure natriuresis in youth.

BACKGROUND: The contribution of stress to obesity-related cardiovascular disease is uncertain. The purpose of this study was to examine the influence of body composition on stress-induced pressure natriuresis. METHODS: Dual energy x-ray absorptiometry was performed in 127 African American and white youths to assess lean body mass (LBM), fat mass (FM), and total percentage of body fat (%BF). The stress protocol was comprised of a 2-h baseline period, 1-h video game competition stressor, and 2-h recovery period. Blood and urine samples were collected hourly and blood pressure (BP) was obtained at 15-min intervals. RESULTS: Both BP and urinary sodium excretion(U(Na)V) increased from baseline to stress and returned to prestress levels after stress (P = .001 for each). The BP levels and changes were positively correlated with LBM. In contrast, levels and changes in sodium excretion U(Na)V were inversely correlated with FM and %BM. Multiple regression analyses that included ethnicity, sex, angiotensin II (Ang II), and measures of body composition in the models indicated the following: a) LBM was the best predictor of stress systolic BP and independently contributed with ethnicity to stress diastolic BP; b) ethnicity was the only independent predictor of the stress-related change in systolic and diastolic BP; c) LBM was the only independent predictor of the change in BP from stress to recovery for both systolic and diastolic BP; and d) total percent body fat accounted for 11.2% of the variance of stress U(Na)V, with Ang II contributing an additional 6.1%. CONCLUSIONS: Based on the results of this study, ethnicity and body composition are related to stress-induced pressure natriuresis.

Absorptiometry, Photon↗

Involvement of the renal kallikrein-kinin system in K(+)-induced diuresis and natriuresis in anesthetized rats.

Intravenous infusion of a high-K(+) solution (67.5 mM KCl, 67.5 mM NaCl) to anesthetized rats increased urine volume by 47.6% after 60 min, compared with infusion of a Na(+) solution (135 mM NaCl). This treatment also increased urinary excretion of Na(+) by 32.2%, in parallel with an increase in excretion of K(+) or Cl(-). Urinary excretion of kallikrein increased within 60 min after the start of K(+) infusion. A bradykinin B(2) receptor antagonist, 8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-me thylamino ]-2,6-dichlorobenzyloxy]-2-methylquinoline (FR173657; 1.0 mg/kg, i.v. ), inhibited the K(+)-induced diuresis and natriuresis by 41.0% and 26.7%, respectively. These results indicate that K(+) load induces diuresis and natriuresis through the renal kallikrein-kinin system in rats.

Anesthesia↗

Natriuresis and the extracellular volume expansion by hypertonic saline.

BACKGROUND: The mechanisms governing the duration of the extracellular fluid volume (ECF) expansion as a result of intravenous infusion of hypertonic saline solution are poorly understood. We hypothesized that the duration is closely related to the sodium excretion. MATERIALS AND METHODS: Six conscious splenectomized ewes with a mean body weight of 30 kg were given an intravenous infusion of 4 ml x kg(-1) of 7.5% saline solution on two occasions, one over a period of 5 min and another over a period of 20 min. Mass balance and volume kinetic calculations of the distribution and elimination of fluid were performed after repeated sampling of the plasma sodium concentration and the urinary excretion of water and sodium during 3 h. RESULTS: On considering the addition of sodium to and its excretion from the body, the plasma sodium concentration indicated a 10% dilution of the extracellular space. The volume expansion decayed at an average rate of 20% of the volume expansion per hour, which, however, varied greatly in the animals, depending on their capacity to excrete sodium. After 1 h, increasing natriuresis promoted translocation of water into the cells, which amounted to 25-35% of the total elimination. Computer simulations indicated that tripled natriuresis (up to approximately 750 mmol l(-1)) would increase the rate of elimination to 45% of the volume expansion per hour. CONCLUSION: The sodium excretion was inversely proportional to the duration of the extracellular volume expansion by 7.5% saline.

Animals↗

Natriuresis after cardiopulmonary bypass: relationship to urodilatin, atrial natriuretic factor, antidiuretic hormone, and aldosterone.

OBJECTIVE: Recent studies suggest that urodilatin from the kidneys rather than atrial natriuretic factor from the heart is the more important member of the family of natriuretic peptides involved in the normal regulation of renal sodium and water excretion. We thus examined the relationship between natriuresis, urodilatin, and atrial natriuretic factor in patients after cardiopulmonary bypass, a procedure known to increase levels of atrial natriuretic factor significantly. METHODS: Excretion rates of sodium and water were correlated with the excretion of urodilatin and with circulating levels of atrial natriuretic factor, antidiuretic hormone, aldosterone, and plasma renin activity during a period of 16 hours in 12 patients having had coronary artery bypass operations and with approximately a 400% elevation in levels of atrial natriuretic factor. RESULTS: Natriuresis did not correlate with atrial natriuretic factor, antidiuretic hormone, aldosterone, or plasma renin activity. Excretion rates of urodilatin, however, correlated significantly with excretion rates of sodium (r = 0.74, p = 0.03), urine flow (r = 0.83, p = 0.01), and with levels of serum sodium (r = 0.82, p = 0.01). CONCLUSION: These results suggest an important role for urodilatin, greater than that of atrial natriuretic factor, in the regulation of renal excretion of sodium and water after cardiopulmonary bypass surgery.

Adult↗

Impaired saline-stimulated diuresis and natriuresis in the conscious hypertensive glucose-intolerant rat.

BACKGROUND: A major complication of type 2 diabetes is renal dysfunction, a condition that worsens with coexistence of systemic hypertension. However, less is known regarding the renal impact of the prediabetic condition characterized by glucose intolerance. Therefore, we tested the hypothesis that chronic glucose intolerance leads to abnormal renal function, a condition also exacerbated by concurrent systemic hypertension. METHODS: A rat model of concomitant NaCl-sensitive hypertension and glucose intolerance was used to study renal function. Glucose intolerance was produced by administering streptozotocin to neonatal Wistar-Kyoto rats, and systemic hypertension was induced by combining dietary NaCl excess with unilateral nephrectomy. Hemodynamic and renal excretory responses were determined in conscious animals before and after administration of a 30-min isotonic saline challenge (5% of body weight, intravenously). RESULTS: Nine-month-old glucose-intolerant rats fed a normal NaCl diet did not manifest impairment in saline-stimulated diuresis and natriuresis. By contrast, 3-month-old glucose-intolerant rats fed a high NaCl diet displayed an exaggerated diuretic and natriuretic response to a saline challenge. Although saline-stimulated diuresis and natriuresis were enhanced in the hypertensive rats, they were reduced in the hypertensive glucose-intolerant animals. The reduction in renal excretory function of the latter group was caused by alterations in both glomerular function and tubular reabsorption of fluid and sodium. CONCLUSIONS: The coexistence of systemic hypertension and glucose intolerance result in impaired renal excretory function. This defect could be important, as hypertension can develop before the onset of overt type 2 diabetes.

Animals↗

Natriuresis and "dilutional" hyponatremia after infusion of glycine 1.5%.

STUDY OBJECTIVE: To challenge the view that the hyponatremia resulting from absorption of glycine 1.5% is attributed to the expansion of the extracellular fluid (ECF) volume, and that the change in serum sodium is therefore widely used to calculate the amount of irrigant absorbed. DESIGN: Retrospective analysis of six studies. SETTING: University-affiliated hospital. MEASUREMENTS: Approximately 1.2 L of glycine 1.5% was infused in 23 volunteers (two studies), 1 L in 10 prostatectomy patients, 2.4 L in 6 sheep, 4 L in 6 other sheep, and 3 L in 9 piglets. The distribution of the irrigant water was estimated from the difference between the measured and the expected serum sodium levels, taking into account the urinary losses of sodium and water. MAIN RESULTS: Between 30% and 50% of the irrigant volume had diffused into the cells 30 minutes after the infusion, and only between 0% and 50% of the fluid remained in the ECF. One hour later, natriuresis accounted for 100% of the residual hyponatremia in the small-volume experiments, and it accounted for approximately 50% in the large-volume experiments. The change in serum sodium could not be used to quantify the small infusion volumes, but the large ones could be quantified fairly accurately if assessed at the very end of the infusion. CONCLUSIONS: Diffusion of water into the cells and natriuresis reduced and prolonged the hyponatremia associated with infusions of glycine 1.5%. This finding makes IV fluid with sodium added a more rational alternative than furosemide in the treatment of fluid overload with this irrigating solution.

Adult↗

Pressure natriuresis in isolated kidneys from hypertension-prone and hypertension-resistant rats (Dahl rats).

Dahl described a strain of rats with genetically controlled propensities for hypertension. Chronic excess salt feeding increased blood pressure in sensitive (s) rats, whereas resistant rats (R) remain normotensive. We tested the pressure natriuretic function (urinary sodium excretion versus perfusion pressure) in isolated kidneys perfused with a cellular medium: in sodium-restricted normotensive sensitive (S0) and resistant (R0) animals; in sensitive rats receiving a high-salt diet for 3 weeks (S3): and in both S and R animals exposed to excess sodium for 7 weeks (R7 and S7). The aim of these studies was to determine if a preset alteration of the pressure natriuretic function might be present in S animals prior to the development of hypertension. Systolic blood pressure in S0, S3, and S7 animals were 123 +/- 4, 136 +/- 2, and 162 +/- 4 mm Hg, respectively, whereas that of R0 and R7 were 121 +/- 5 and 126 +/- 5 mm Hg. An increase of the perfusion pressure of isolated kidneys from 105 to 185 mm Hg in stepwise fashion resulted in a pressure natriuresis whose slope was similar in R0 and S0 animals. Of interest was that the pressure natriuretic function slope of kidneys from R0 (low sodium) and R7 (high sodium) rats was as predicted by the Guyton system analysis of normal blood pressure control Micropuncture of the proximal nephrons demonstrated that the origin of the natriuresis resulted from a site beyond the accessible proximal tubule. Results from S7 kidneys contrasted with all others in that the natriuretic response was depressed (P less than 0.01), which resulted from significantly lower filtration rates at higher perfusion pressures. We concluded (1) in normal R rats, the pressure natriuretic function is that predicted by the Guyton hypothesis, (2) Dahl S animals have no preset abnormality of this function until hypertension is present for some time, and (3) a depression of the pressure natriuretic function may aggravate hypertension in S rats once high blood pressure has persisted.

Animals↗

Attenuated pressure natriuresis in hypertensive rats.

We studied the isolated blood-free perfused nonclipped kidneys from the 2-kidney Goldblatt hypertensive rat model (GHR) to evaluate intrinsic excretory responses to changes in perfusion pressure. We examined kidneys from 10 control rats (in vivo systolic BP 110 +/- 3.6 mm Hg), from 9 rats with nonmalignant hypertension (HBP) (in vivo systolic BP 158 +/- 6.5 mm Hg), and from 5 rats with malignant HBP (in vivo systolic BP 183 +/- 6.4 mm Hg). We found that at all levels of perfusion pressure, the renal vascular resistances were significantly higher and glomerular filtration rate (GFR) lower in kidneys from hypertensive rats than in kidneys from control rats. Kidneys from hypertensive rats had lower urinary excretion of sodium (UNaV) and urine flow than kidneys from control rats at all levels of pressure above 100 mm Hg. The most striking differences in all functional parameters were noted in kidneys from rats with malignant HBP. Kidneys from both hypertensive and control rats failed to show changes in vascular resistance in response to Saralasin. We conclude that the nonclipped kidney in GHR exhibits a blunted natriuresis in response to elevated perfusion pressure which occurs in the absence of angiotensin II (AII) and renin substrate. This diminished pressure natriuresis may be caused partly by the lower GFR and by reduced pressure transmission due to greater renal vascular resistance and thus may be partially responsible for the maintenance of the hypertensive state.

Animals↗

Pressure natriuresis and prostaglandin secretion by perfused rat kidney.

Isolated rat kidneys respond to elevations of perfusion pressure with an increase in glomerular filtration rate (GFR), filtration fraction (FF), and sodium excretion (UNaV) and a fall in fractional sodium reabsorption (FRNa). Significant linear correlations exist between each of these dependent variables and the renal artery pressure (P). In control kidneys, pressure natriuresis is seen to result both from an increase in filtered sodium load and a decrease in FRNa. In kidneys treated with indomethacin in doses which curtail the release into the perfusate of prostaglandin E2 (PGE2) and the prostacyclin metabolite, 6-keto-PGF1 alpha, the regression lines relating GFR, FF, and UNaV to P are shifted to the right. Thus, prostaglandin-inhibited kidneys require higher pressures than control kidneys to maintain comparable rates of filtration and sodium excretion. Total renal vascular resistance (RVR) is also higher in inhibited kidneys. These findings suggest that in the isolated perfused rat kidney, prostaglandins promote pressure natriuresis by maintaining afferent arteriolar dilation. Their inhibition leads to afferent constriction, which raises RVR, lowers FF and GFR, and reduces sodium excretion.

6-Ketoprostaglandin F1 alpha↗

Role of renal hemodynamics in the exaggerated natriuresis of essential hypertension.

Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essential hypertensives and six normotensive healthy controls. Before and during WI we measured mean arterial pressure (MAP), urine flow (V/min), sodium (UNaV) and potassium (UKV) excretion, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and intrarenal (wedged) venous pressure (IRVP). In comparison with normotensive controls, the exaggerated natriuretic response in hypertensives (P less than 0.05 for UNaV during WI) was associated with an enhanced vasodilating response as demonstrated by a greater increase in ERPF (P less than 0.05) and by a more pronounced fall in calculated renal precapillary resistances (P less than 0.05). A more significant increase in IRVP was found in hypertensive group (P less than 0.05). Glomerular filtration rate (GFR) did not change in either group during WI. MAP, unchanged in normotensives, was significantly reduced in hypertensives (P less than 0.05), while remaining in the hypertensive range. These findings suggest that intrarenal physical factors play a major role in determining the exaggerated natriuresis during WI in hypertensive man.

Adult↗

The effect of dopamine receptor blockade on natriuresis is dependent on the degree of hypervolemia.

A number of different physiological factors and systems have been suggested to be responsible for the natriuretic effect following acute isotonic volume expansion (VE). The variation in suggestions may depend on the prevailing status of the systems governing fluid and electrolyte balance before VE, on the expansion medium and on the rate and degree of VE. A study was performed to determine whether the previously documented attenuating effect of dopamine receptor blockade on natriuresis induced by VE is dependent on the degree of hypervolemia. Anesthetized rats were pretreated with the dopamine receptor blockers haloperidol (1 mg.kg-1 body weight, i.p.), SCH 23390 (30 micrograms.hr-1.kg-1 i.v.) or vehicle and then subjected to VE at 2, 5 or 10% of body weight per hour. VE at 2, 5 and 10% increased sodium excretion in vehicle-pretreated animals 6-, 29- and 130-fold, respectively. In the haloperidol-pretreated animals the natriuretic response (accumulated sodium excretion) to VE was attenuated by 67% (P less than 0.05), 46% (P less than 0.05) and 22% (NS) at the three degrees of expansion, respectively. The corresponding attenuation in SCH 23390-treated animals were 60% (P less than 0.05), 56% (P less than 0.05) and 19% (NS), respectively. The gradual decrease in attenuation indicates that at varying degrees of hypervolemia, different physiological systems contribute differently to the renal natriuretic response. The dopamine system seems to be relatively more important in promoting natriuresis at the lower (physiological) range of hypervolemia whereas in the high range other factors have a greater impact.

Animals↗

Renal nerves and the natriuresis following unilateral renal exclusion in the rat.

Both acute unilateral nephrectomy (AUN) and acute ureteral pressure elevation (UPE) stimulate sodium excretion (UNaV) from the contralateral kidney, a response which in each case is interrupted by prior denervation of either kidney. Yet the natriuresis after AUN is known to be related to an increase in the plasma concentration of a gamma-melanocyte stimulating hormone (gamma-MSH)-like peptide. In anesthetized rats, sham AUN had no effect on contralateral UNaV, and plasma immunoreactive (IR) gamma-MSH concentration was 10.6 +/- 3.0 (SD) fmol/ml. In rats with intact renal innervation, UNaV more than doubled after AUN (P less than 0.001), and IR-gamma-MSH was increased to 14.9 +/- 4.6 fmol/ml (P less than 0.025). Unilateral renal denervation led to the expected increase in ipsilateral and decrease in contralateral UNaV, and neither sham AUN nor AUN of the denervated of innervated kidney influenced UNaV. In all three of these groups, IR-gamma-MSH concentration was reduced below the sham or post-AUN values seen in rats with innervated kidneys, to 4.9 +/- 3.3, 3.8 +/- 3.4, and 2.8 +/- 3.5 fmol/ml, respectively (P less than 0.001 for all). These results suggested that removal of renal afferent nerve input by renal denervation lowered basal IR-gamma-MSH activity and prevented the stimulated level normally seen after AUN. To examine the effect of stimulating afferent renal nerve activity, we carried out UPE, a maneuver known to increase ipsilateral afferent renal nerve traffic through activation of renal mechanoreceptors, as well as cause a natriuresis from the contralateral kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of neurohypophyseal antagonists in postnephrectomy natriuresis in male rats.

Acute unilateral nephrectomy (AUN) in anesthetized male Lewis x DA rats induced rapid and consistent increases in electrolyte and fluid excretion by the remaining kidney during the first hours. Continuous infusion of a vasopressin (AVP) V1-receptor antagonist d(CH2)5Tyr(Me)AVP (V1-ant) reduced renal electrolyte and fluid excretion before and after AUN to a similar extent, whereas an oxytocin (OT)-receptor antagonist [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-OT (CAP) at the same dose selectively attenuated the increase in sodium excretion after AUN. The plasma concentration of OT rose significantly after AUN (9.16 +/- 1.4 to 21.45 +/- 5.07 pg.ml-1). A similar OT level obtained by infusion of OT mimicked the renal responses to AUN without elevating blood pressure; however, only CAP but not V1-ant efficiently reversed OT-induced natriuresis. Also, the infusion of CAP at the same dose produced no effects on the rise of blood pressure caused by AVP while the infusion of the V1-ant prevented such a rise. Thus, CAP reduced the natriuresis after AUN by interfering with OT- and not V1-receptors. In conclusion, evidence is presented, for the first time, concerning the major role of OT receptors in the acute readjustment of the renal sodium excretion after AUN, and a synergistic role for AVP in terms of the general magnitude of renal excretion.

Animals↗