Central mu opioids mediate differential control of urine flow rate and urinary sodium excretion in conscious rats

We have recently developed an experimental approach to study central opioid control of renal function in anesthetized rats. This model system uses the intravenous infusion of the α2-agonist xylazine to enhance basal levels of urine flow rate and urinary sodium excretion in ketamine-anesthetized rats. This study examined the contribution of central and peripheral α2-adrenergic receptor mechanisms in mediating the enhanced renal excretory responses produced by xylazine. In ketamine-anesthetized rats, the enhanced levels of urine flow rate and urinary sodium excretion produced by the intravenous infusion of xylazine were reversed by the intravenous bolus injection of the α2-adrenoceptor antagonist yohimbine but not by the α1-adrenoceptor antagonist terazosin. In separate animals the intracerebroventricular administration of yohimbine only reduced urine flow rate by ∼50% but did not alter urinary sodium excretion. The decrease in urine flow rate produced by intracerebroventricular yohimbine was reversed by the intravenous injection of a selective V2-vasopressin receptor antagonist. In a separate group of ketamine- and xylazine-anesthetized rats, the bilateral microinjection of yohimbine into the hypothalamic paraventricular nucleus (PVN) also significantly decreased urine flow rate by 54% without altering urinary sodium excretion. The microinjection of the β-adrenoceptor antagonist propranolol into the PVN did not alter either renal excretory parameter. These results suggest that during intravenous infusion, xylazine increases urine flow rate by activating α2-adrenergic receptors in the PVN, which in turn decrease vasopressin release. The ability of α-adrenergic mechanisms in the PVN to selectively influence the renal handling of water, but not sodium, may contribute to the reported dissociation of the natriuretic and diuretic responses of α2-adrenoceptor agonists.

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Blunted natriuresis to atrial natriuretic peptide in chronic sodium-retaining disorders

AJP Renal Physiology ◽

10.1152/ajprenal.1987.252.5.f865 ◽

1987 ◽

Vol 252 (5) ◽

pp. F865-F871 ◽

Cited By ~ 4

Author(s):

J. P. Koepke ◽

G. F. DiBona

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Flow Rate ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Urine Flow Rate ◽

Atrial Natriuretic

Renal responses to atrial natriuretic peptide were examined in conscious dogs with congestive heart failure (tricuspid insufficiency) and in conscious rats with nephrotic syndrome (adriamycin). Heart-failure dogs displayed elevated atrial pressure and heart weights, blunted natriuresis to a saline load, and ascites. Nephrotic rats displayed proteinuria, hypoproteinemia, sodium retention, and ascites. In control animals, atrial natriuretic peptide increased absolute and fractional urine flow rate and urinary sodium excretion. Although atrial natriuretic peptide increased absolute and fractional urine flow rate and urinary sodium excretion in conscious heart-failure dogs and nephrotic rats, the responses were markedly blunted. In heart-failure dogs, infusion of atrial natriuretic peptide increased plasma concentrations of norepinephrine and epinephrine. In nephrotic rats, renal denervation reversed the blunted diuretic and natriuretic responses to atrial natriuretic peptide. Mean arterial pressure, glomerular filtration rate, and p-aminohippurate clearance were affected similarly by atrial natriuretic peptide in heart-failure dogs or nephrotic rats vs. control animals. Conscious congestive heart-failure dogs and conscious nephrotic rats have blunted diuretic and natriuretic responses to atrial natriuretic peptide.

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Excretion of endogenous digoxin-like immunoreactive factors in human urine is a function of urine flow rate.

Clinical Chemistry ◽

10.1093/clinchem/34.5.960 ◽

1988 ◽

Vol 34 (5) ◽

pp. 960-964 ◽

Cited By ~ 4

Author(s):

B A Siegfried ◽

R Valdes

Keyword(s):

Urinary Excretion ◽

Flow Rate ◽

Human Urine ◽

Sodium Excretion ◽

Salt Intake ◽

Fractional Excretion ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Urine Flow Rate ◽

Healthy Humans

Abstract We studied the effect of varying water and salt intake on the renal excretion of endogenous digoxin-like immunoreactive factors (DLIF). DLIF were measured in human urine and serum by competitive displacement of 125I-labeled digoxin from anti-digoxin antibodies. Diuresis was selectively induced in normal healthy humans by acute water ingestion, and natriuresis was preferentially induced by acute saline ingestion. We found the amount of endogenous immunoreactivity excreted in urine to be correlated with urine flow rate but not with urinary sodium excretion. Urinary excretion of DLIF, normalized to creatinine, was 3.6-fold greater at a urine flow rate of 5.5 mL/min than at 0.5 mL/min. On the other hand, saline intake increased urine flow rate 1.9-fold and increased sodium excretion threefold, but did not affect urinary excretion of DLIF. Fractional excretion of DLIF was linearly related to fractional excretion of water. This study demonstrates that normalization of DLIF values to urinary creatinine does not make DLIF excretion independent of urine flow rate and underscores the need for information on urine flow rate when DLIF measurements in urine are being interpreted.

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Fasting induces denervation natriuresis in the conscious rat

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.5.f753 ◽

1985 ◽

Vol 249 (5) ◽

pp. F753-F758 ◽

Cited By ~ 2

Author(s):

G. Szenasi ◽

P. Bencsath ◽

L. Szalay ◽

L. Takacs

Keyword(s):

Sodium Excretion ◽

Left Kidney ◽

Extracellular Fluid ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Urinary Sodium ◽

Renal Nerves ◽

Sham Operation ◽

Conscious Rats ◽

Fasted Rats

The participation of renal nerves in the regulation of sodium excretion was studied in fed and overnight-fasted rats subjected to acute or chronic left kidney denervation or sham operation. Clearance experiments were performed on conscious restrained animals. Urine flow, glomerular filtration rate (GFR), and urinary sodium excretion were not different in left and right kidneys of sham-operated rats. In fed conscious rats, urine flow, GFR, and urinary sodium excretion of innervated (I) and denervated (D) kidneys were similar. In fasted conscious rats, significant denervation natriuresis was observed after both acute (I, 1.06 +/- 0.27; D, 1.56 +/- 0.40 mumol . min-1 . g-1, P less than 0.05) and chronic (I, 1.55 +/- 0.19; D, 2.20 +/- 0.18 mumol . min-1 . g-1, P less than 0.01) renal sympathectomy, whereas urine flow and GFR in I and D kidneys were not different. Additional experiments revealed that extracellular fluid and plasma volumes of fasted rats were decreased by approximately 10% compared with those of fed animals due to a significant overnight natriuresis and negative water balance. In fed conscious rats, the renal nerves do not seem to participate in the regulation of sodium excretion. The presence of denervation natriuresis in conscious fasted rats suggests that renal nerves are involved in sodium conservation during fasting to maintain extracellular fluid and plasma volume.

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Renorenal reflex responses to mechano- and chemoreceptor stimulation in the dog and rat

AJP Renal Physiology ◽

10.1152/ajprenal.1984.246.1.f67 ◽

1984 ◽

Vol 246 (1) ◽

pp. F67-F77 ◽

Cited By ~ 34

Author(s):

U. C. Kopp ◽

L. A. Olson ◽

G. F. DiBona

Keyword(s):

Blood Flow ◽

Renal Function ◽

Renal Blood Flow ◽

Flow Rate ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Secretion Rate ◽

Renin Secretion ◽

Urine Flow Rate

The renal functional effects of renal mechano- (MR) and chemoreceptor (CR) stimulation were examined in dogs and rats. In dogs increasing ureteral pressure (increases UP) increased ipsilateral (ipsi) renal blood flow and renin secretion rate, decreased contralateral (contra) renal blood flow, but did not affect contra renal excretion or renin secretion rate. Increasing renal venous pressure (increases RVP) increased ipsi renin secretion rate but did not affect contra renal function. Retrograde ureteropelvic perfusion with 0.9 M NaCl at unchanged UP did not affect either ipsi or contra renal function. In rats,increases UP and retrograde ureteropelvic perfusion with 0.9 M NaCl at unchanged UP did not affect mean arterial pressure, heart rate, contra renal blood flow, or glomerular filtration rate but increased contra urine flow rate and urinary sodium excretion. Increasing ureteral pressure with 0.1 M NaCl increased contra urine flow rate and urinary sodium excretion, whereas retrograde ureteropelvic perfusion with 0.1 M NaCl was without effect. Thus increases UP and retrograde ureteropelvic perfusion with 0.9 M NaCl stimulated renal MR and CR, respectively. The contra diuretic and natriuretic responses to renal MR and CR stimulation were abolished by either ipsi or contra renal denervation. Renal MR and CR stimulation increased ipsi afferent renal nerve activity (RNA) and decreased contra efferent RNA. These results indicate that in dogs renal MR stimulation results in a modest contralateral excitatory renorenal reflex, whereas in rats renal MR and CR stimulation produce a contralateral inhibitory renorenal reflex.

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Role of atrial natriuretic peptide in volume-expansion natriuresis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.2.r310 ◽

1986 ◽

Vol 251 (2) ◽

pp. R310-R313 ◽

Cited By ~ 4

Author(s):

T. R. Schwab ◽

B. S. Edwards ◽

D. M. Heublein ◽

J. C. Burnett

Keyword(s):

Atrial Natriuretic Peptide ◽

Sodium Excretion ◽

Volume Expansion ◽

Fractional Excretion ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Urinary Sodium ◽

Right Atrial ◽

Fractional Excretion Of Sodium

Studies were performed to investigate the role of circulating atrial natriuretic peptide (ANP) in acute volume-expansion natriuresis. Sham-operated (SHAM, n = 6) and right atrial appendectomized (ATRX, n = 12) anesthetized rats underwent acute volume expansion with isoncotic albumin. After equilibration and control periods, volume expansion increased urine flow rate, urinary sodium excretion, fractional excretion of sodium, and circulating ANP. Absolute increases in urine flow rate (delta 46 +/- 4 SHAM; delta 25 +/- 5 microliter/min ATRX), urinary sodium excretion (delta 9.48 +/- 1.01 SHAM; delta 4.77 +/- 1.03 mueq/min ATRX), fractional excretion of sodium (delta 3.16 +/- 0.53 SHAM; delta 1.65 +/- 0.32% ATRX), and ANP (delta 303.3 +/- 35.9 SHAM; delta 156.6 +/- 26.0 pg/ml ATRX) were significantly reduced by right atrial appendectomy. No significant differences in mean arterial pressure, central venous pressure, or glomerular filtration rate during volume expansion were observed between groups. These studies support the hypothesis that right atrial appendectomy in the rat attenuates acute volume expansion-induced increases in circulating ANP and urinary sodium excretion and that the natriuresis of acute volume expansion is mediated in part by an increase in circulating ANP.

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Atrial natriuretic hormone effect on renal function and aldosterone secretion in sodium depletion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.6.r867 ◽

1988 ◽

Vol 255 (6) ◽

pp. R867-R873

Author(s):

Y. Shenker

Keyword(s):

Renal Function ◽

Sodium Excretion ◽

Low Dose ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Plasma Aldosterone ◽

Urinary Sodium ◽

Aldosterone Secretion ◽

Natriuretic Hormone ◽

Atrial Natriuretic Hormone

The effects of atrial natriuretic hormone (ANH) on aldosterone secretion and renal function have been well documented, but the physiological role of ANH is still unknown. To address this issue, eight normal men were infused for 4 h with low-dose (1.1 pmol.kg-1.min-1) human [Ser-Tyr28]ANH after 3 days of low-salt (LS) diet. The same subjects were also studied with placebo infusion on LS and high-salt (HS) diet. ANH infusion caused doubling of urine flow, a fourfold increase in urinary sodium excretion, and a slight increase in potassium excretion. Immunoreactive ANH levels increased from 3.1 +/- 0.5 to 21.0 +/- 1.9 pmol/l during ANH infusion. ANH infusion suppressed plasma renin activity (PRA) to one-third of the basal value, and plasma aldosterone was suppressed from 46.5 +/- 6.5 to 20.9 +/- 2.6 ng/dl. Low-dose ANH infusion caused a marked increase in urine flow and urinary sodium excretion and prominent suppression of PRA and plasma aldosterone in sodium-depleted subjects. These results suggest a physiological significance of ANH in regulation of kidney function and aldosterone secretion.

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Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.5.r1450 ◽

2001 ◽

Vol 280 (5) ◽

pp. R1450-R1456 ◽

Cited By ~ 13

Author(s):

Tomoyuki Yamasaki ◽

Isao Tamai ◽

Yasuo Matsumura

Keyword(s):

Receptor Antagonist ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Urinary Sodium ◽

Renal Nerve ◽

Anesthetized Dogs ◽

Induced Changes ◽

Antidiuretic Action

To investigate the possible involvement of histamine H3 receptors in renal noradrenergic neurotransmission, effects of (R)alpha-methylhistamine (R-HA), a selective H3-receptor agonist, and thioperamide (Thiop), a selective H3-receptor antagonist, on renal nerve stimulation (RNS)-induced changes in renal function and norepinephrine (NE) overflow in anesthetized dogs were examined. RNS (0.5–2.0 Hz) produced significant decreases in urine flow and urinary sodium excretion and increases in NE overflow rate (NEOR), without affecting renal hemodynamics. When R-HA (1 μg · kg−1 · min−1) was infused intravenously, mean arterial pressure and heart rate were significantly decreased, and there was a tendency to reduce basal values of urine flow and urinary sodium excretion. During R-HA infusion, RNS-induced antidiuretic action and increases in NEOR were markedly attenuated. Thiop infusion (5 μg · kg−1 · min−1) did not affect basal hemodynamic and excretory parameters. Thiop infusion caused RNS-induced antidiuretic action and increases in NEOR similar to the basal condition. When R-HA was administered concomitantly with Thiop infusion, R-HA failed to attenuate the RNS-induced antidiuretic action and increases in NEOR. However, in the presence of pyrilamine (a selective H1-receptor antagonist) or cimetidine (a selective H2-receptor antagonist) infusion, R-HA attenuated the RNS-induced actions, similarly to the case without these antagonists. Thus functional histamine H3 receptors, possibly located on renal noradrenergic nerve endings, may play the role of inhibitory modulators of renal noradrenergic neurotransmission.

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Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.2.h679 ◽

1997 ◽

Vol 272 (2) ◽

pp. H679-H687

Author(s):

M. Naitoh ◽

H. Suzuki ◽

K. Arakawa ◽

A. Matsumoto ◽

A. Ichihara ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Receptor Antagonist ◽

Flow Rate ◽

Ace Inhibitors ◽

Sodium Excretion ◽

Filtration Rate ◽

Urinary Sodium Excretion ◽

Urine Flow ◽

Ang Ii ◽

Low Renin Hypertension

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.

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Natriuretic and diuretic effects of infusion of atrial natriuretic factor in conscious dogs

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.4.f565 ◽

1989 ◽

Vol 257 (4) ◽

pp. F565-F573

Author(s):

J. Ohanian ◽

M. A. Young ◽

Y. T. Shen ◽

R. Gaivin ◽

S. F. Vatner ◽

...

Keyword(s):

Amino Acid ◽

Arterial Pressure ◽

Flow Rate ◽

Plasma Levels ◽

Sodium Excretion ◽

Atrial Natriuretic Factor ◽

Urine Flow ◽

Urine Flow Rate ◽

Conscious Dogs ◽

Natriuretic Factor

We studied the effects of 30-min infusions of the synthetic 25-amino acid atrial natriuretic factor [ANF-(102-126)] and the 28-amino acid ANF-(99-126) at 0.1 and 0.3 micrograms.kg-1.min-1 on urine flow rate, sodium excretion, and arterial pressure in conscious dogs. Each dose was administered on a separate day following a 1-h stabilization period. We also compared the effects of 60-min infusions of ANF, 0.01 micrograms.kg-1.min-1, or water infusion on separate days in conscious dogs. Arterial pressure was reduced in a dose-dependent fashion, reaching statistical significance at a dose of 0.3 micrograms.kg-1.min-1. During the 0.01-micrograms.kg-1.min-1 infusion, the plasma concentration of ANF rose approximately threefold (from 68 +/- 7 to 207 +/- 14 pg/ml), with no change in urine flow rate, sodium excretion, or arterial pressure. At a dose of 0.1 micrograms.kg-1.min-1, urine flow increased (P less than 0.05) by 0.41 +/- 0.15 ml/min, and sodium excretion rose by 72 +/- 24 mu eq/min, but not significantly, whereas plasma ANF levels rose to 1,236 +/- 229 pg/ml. At the highest dose of ANF (0.3 micrograms.kg-1.min-1) urine flow rose by 0.62 +/- 0.16 ml/min, P less than 0.05, and sodium excretion rose by 139 +/- 30 mu eq/min, P less than 0.05, whereas plasma levels of ANF rose to 2,436 +/- 320 pg/ml. In contrast, volume loading with dextran increased urine flow by 3.5 +/- 1.3 ml/min, P less than 0.05, and sodium excretion by 439 +/- 147 mu eq/min, P less than 0.05, whereas ANF rose to only 320 +/- 69 pg/ml. These results suggest that, in the conscious dog, ANF does not cause significant diuretic or natriuretic effects until plasma levels are markedly above those observed in physiological conditions. A possible explanation for the difference between this and previous studies is that the renal effects of ANF, at physiological plasma levels, are indirect and thus dependent on autonomic and hormonal (angiotensin, vasopressin, and aldosterone levels) factors governing the renal function of the animal.

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