Effects of atrial natriuretic peptides and furosemide in conscious dogs

Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diuretic dogs. The two substances were injected intravenously (1.08 micrograms/kg in 3 min) or ANF(8-33) was infused (0.2 microgram/kg X min in 20 min). The effects were compared to those of an equinatriuretic dose of furosemide (1.0 microgram/kg X min). Injections caused increases in sodium excretion, diuresis, and osmolar clearance. No significant change in exogenous creatine clearance (CCREA) occurred. Infusion of ANF(8-33) decreased blood pressure by 14% (P less than 0.01) and increased sodium excretion by a factor of 10 (P less than 0.01). The natriuresis was a function of increases in diuresis and urinary sodium concentration, the latter by a factor of 6 (P less than 0.01). Diuresis and free-water clearance (CH2O) increased by 60% (P less than 0.01), but urine osmolality did not change significantly. After the infusion a significant decrease in PAH clearance (CPAH) (P less than 0.01) was observed. Filtration fraction (FF) did not change. The furosemide natriuresis appeared later than that of ANF without significant deviations in diuresis, CH2O, CCREA, CPAH, and FF; urine osmolality increased by 35% (P less than 0.01). The effects of ANF(8-33) differ from those of furosemide in several ways. First, the onset of natriuresis is faster, second, the natriuresis is associated by marked increases in diuresis and free-water clearance but not in urine osmolality; and third, natriuresis is followed by a reduction in renal blood flow. The rapid natriuresis of ANF can occur without changes in glomerular filtration rate.     

Effects of atrial natriuretic factor on urinary concentration of catecholamines and renin secretion in dogs

This study evaluated the effects of synthetic atrial natriuretic factor (ANF) on renal hemodynamics, urinary excretion of electrolytes, norepinephrine (NE), and dopamine (DA); and renal production of renin in anesthetized dogs. Following a bolus (1 micrograms/kg body weight) and infusion (0.1 microgram/kg/min) for 30 min, there was significant increase in urine flow (220 +/- 41%), glomerular filtration rate (72 +/- 14%), and urinary sodium excretion (170 +/- 34%). There was a decrease in renin secretory rate and the concentration ratio of urine NE to DA following ANF was decreased (p less than 0.05). These data suggest that ANF decreases renal production of NE and renin.     

Propranolol induces acute natriuresis by beta blockade and dopaminergic stimulation.

dl-Propranolol (0.8-1.6 mg/kg - h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin-angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by beta blockade and requires post ganglionic nerve function but is independent of alpha receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal beta blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking beta receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.     

Effects of substance P on renin release and renal function in anesthetized dogs.

Substance P (SP), a naturally occuring undecapeptide with hypotensive, vasodilatory and smooth muscle stimulating properties, was infused intravenously or intrarenally into anesthetized dogs. Infusions of SP intravenously suppressed renin secretion rate (RSR) from 204±45 to 52±18 ng/min (p < 0.02) at an infusion rate of 0.5 ng/kg/min, and to 50±22 ng/min (p < 0.05) at 5 ng/kg/min. When the concentration of SP was further increased to 50 ng/kg/min, RSR increased to a level above the control value (728±81, p < 0.01). Intrarenal infusion of SP produced similar changes in renin release. At infusion rates of 0.5 ng/kg/min and 5 ng/kg/min, RSR was suppressed from 145±18 to 56±18 ng/min (p < 0.05) and to 26±8 ng/min (p < 0.01) respectively. At 50 ng/kg/min, RSR increased to 251±59 (p > 0.1). Both intravenous and intrarenal administration of the peptide significantly lowered arterial blood pressure at the highest two doses. Intrarenal infusion of SP resulted in a significant dose-related increase in urine volume, sodium and potassium excretion, and renal blood flow. In contrast, intravenous infusions did not alter these parameters. Thus SP suppresses renin release in the presence and in the absence of diuresis, natriuresis, and vasodilation.     

The effect of lidocain on the renal function

The evidence supporting a role for direct neurogenic control of renal function was investigated in twenty anaesthetized dogs. Unilateral renal sympathectomy was induced by 0.5 mg/kg/min of lidocain infusion into the left renal artery and the kidney function changes were compared to those observed in the right non infused kidney. The renal parameters were similar in the kidneys during the control periods. 0.5 mg/kg/min of lidocain infusion into the left renal artery resulted in significant reductions of the RBF, GFR, urine and sodium excretion in the left kidney. The intrarenal lidocain infusion induced a small decrease of the arterial blood pressure but this can not explain the changes observed in the left kidney. The modifications of the right kidney function during lidocain infusion were significantly less than those observed in the left kidney. Comparing the measured RBF and the renal blood flow calculated by the CPAH in the left kidney during the lidocain infusion, we have found a marked difference, when the decrease of the calculated RBF was greater. We believe that effects of pharmacological denervation can be best explained by the intrarenal hemodinamically mediated changes. The sympathectomy produces a considerable vasoconstriction in the renal cortical vascular bed, subsequently it decreases the RBF, GFR renal sodium and water excretion. But the lidocain blocks the sympathetic nerves influencing the renal medullary vessels and the renal medullary blood flow increases. These observations are not consistent with the notion that renal nerves are at least partially responsible for the natriuresis accompanying salt loading.     

Cardiovascular and renal effects of calcitonin gene-related peptide in hypertensive dogs

The systemic cardiovascular and renal effects of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in conscious normotensive and one-kidney one-clip (1K-1C) hypertensive dogs. beta-hCGRP was infused intravenously at 10 and 50 ng/kg/min for 75-min periods each. Mean arterial pressure did not change significantly (p greater than 0.05) in either group during low dose infusion of beta-hCGRP, but infusion of beta-hCGRP at 50 ng/kg/min produced a fall in mean arterial pressure from 140 +/- 4 to 116 +/- 6 mmHg (p less than 0.05) in the hypertensive dogs (n = 4) and from 100 +/- 4 to 78 +/- 3 mmHg (p less than 0.05) in the normotensive dogs (n = 4). Heart rates increased significantly during infusion of beta-hCGRP in both groups. Also, renal sodium and potassium excretion decreased (p less than 0.05) in the two groups at both the low and high doses of beta-hCGRP. Creatinine clearance was unchanged in normal dogs and decreased (p less than 0.05) in 1K-1C hypertensive dogs at the high rate of beta-hCGRP infusion. The clearance of p-aminohippurate increased approximately 20% (p less than 0.05) in both groups with the low dose infusion of beta-hCGRP but further increases were elicited only in the normotensive dogs in response to the elevation in the beta-hCGRP infusion rate. Plasma renin and aldosterone levels increased (p less than 0.05) above control levels during the maximum hypotensive response to beta-hCGRP infusion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat

Prostaglandin E2, when infused into the renal artery of the dog, is a vasodilator and increases both renal interstitial hydrostatic pressure and sodium excretion. Similar studies in the rat, however, have been inconclusive. The present study examined the effect of prostaglandin E2 infusion into the renal interstitium, by means of a chronically implanted matrix, on renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. Prostaglandin E2 was continuously infused directly into the kidney interstitium to mimic endogenous prostaglandin E2 production by renal cells. The maximum change in each of these parameters occurred when 10(-5) M PGE2 was infused. Renal blood flow increased from 4.70 +/- 0.91 to 5.45 +/- 0.35 ml/min (p less than 0.05) while renal interstitial hydrostatic pressure decreased from 3.9 +/- 0.4 to 2.6 +/- 0.5 mmHg (p less than 0.05) and fractional excretion of sodium decreased from 1.02 +/- 0.20 to 0.61 +/- 0.12% (p less than 0.05). Thus, the present study demonstrates that renal interstitial infusion of prostaglandin E2 increases total renal blood flow but decreases both renal interstitial hydrostatic pressure and urinary sodium excretion in the rat.     

Natriuretic activity of digoxin-like immunoreactive substance extracted from cord blood

It was examined whether the digoxin-like immunoreactive substance (DLIS) extracted from cord blood has a natriuretic activity. The DLIS was prepared from cord blood of healthy fullterm infants by acetone-HCl extraction and a gel filtration column. A solution (solution A) containing 1.0 ng/ml of DLIS or another solution (solution B) consisting of solution A from which the DLIS had been completely absorbed by rat brain synaptosome, a crude digoxin receptor, were infused directly into the renal arteries of rats. Serum and urine were serially sampled. The excretion of sodium into the urine increased gradually after the initiation of infusion and reached a level two or three times higher than that before infusion (p less than 0.05). The infusion of a buffer solution or of the extract from which the DLIS had been absorbed by rat brain synaptosome did not significantly increase the urinary excretion of sodium. Statistical analysis showed a clear difference in the natriuretic activity between solutions A and B (p less than 0.01, p less than 0.05). Well-known natriuretic substances such as atrial natriuretic hormone, prostaglandin E2, F2 alpha, bradykinin and oxytocin dopamine were not detected enough to contribute to natriuresis in the extracts. From this data, we speculated that the DLIS in cord blood has a natriuretic activity and that it plays a role in water and sodium homeostasis in perinatal life.     

Renal effects of dopamine and dopexamine in the newborn anesthetized rabbit.

The renal effects of dopexamine, a new dopaminergic agonist with marked beta 2-adrenergic agonist properties, but no alpha-adrenergic effect, has been studied in 8 newborn New Zealand rabbits, whose renal functional characteristics show close similarities with those of premature infants. Six animals were used as controls. After a control period, dopexamine was infused intravenously at a rate of 4 micrograms/kg per min and after a wash-out period, at 10 micrograms/kg per min. The renal effects of dopamine were studied in similar conditions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by inulin and para-aminohippuric acid clearances, respectively. Dopexamine, 4 micrograms/kg per min, did not induce changes in cardiovascular and renal hemodynamics or in renal functions. At 10 micrograms/kg per min, a significant increase in urine flow rate (25 +/- 5%; p less than 0.01), urine sodium excretion (77 +/- 17%; p less than 0.01) and fractional sodium excretion (69 +/- 25%; p less than 0.05) was observed. The GFR, RPF and renal vascular resistance (RVR) were not affected. Heart rate increased slightly but significantly (8 +/- 3%; p less than 0.05), without change in mean blood pressure (MBP). Dopamine, 4 micrograms/kg per min, decreased slightly albeit significantly MBP (3 +/- 1%; p less than 0.05). At 10 micrograms/kg per min the only renal effect was a significant increase in RVR (19 +/- 6%; p less than 0.02). The different actions of these two dopaminergic agonists in this immature model could be explained by their respective ability to activate electively the adrenergic and dopaminergic peripheral receptors. The natriuretic and diuretic effect of dopexamine in normal immature rabbits, in the absence of changes in RPF or GFR is probably mediated by a direct action of this agent on dopaminergic tubular receptors. Failure of these two drugs to increase RPF may be related to an immaturity of the dopaminergic vascular receptors.     

Possible role of renal prostaglandin E2 in natriuresis associated with supraventricular tachycardia

We investigated the possible role of renal prostaglandin (PG) E2 in natriuresis associated with supraventricular tachycardia (SVT). In five female patients with paroxysmal tachycardia, SVT was artificially induced and then stopped 60 min later. Before, during, and after SVT, plasma levels of arginine vasopressin and atrial natriuretic peptide (ANP) and the urinary excretion of sodium and PGE2 were measured. Polyuria was observed during SVT. However, natriuresis did not occur until immediately after the termination of SVT. During SVT, the plasma levels of arginine vasopressin tended to decrease. When SVT was terminated, the vasopressin levels increased significantly (p less than 0.01). Urinary excretion of PGE2 tended to decrease during SVT and then increased significantly (p less than 0.01) after SVT ended. Urinary excretion of sodium was correlated (r = 0.699, p less than 0.001) with the urinary excretion of PGE2. Plasma ANP increased during SVT, but there was no correlation with urinary sodium excretion. These results suggest that renal PGE2, the biosynthesis of which may be stimulated by a increase in plasma vasopressin, is an important factor contributing to the natriuresis observed after the end of SVT.     

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 μg/min) or bradykinin (5 μg/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.     

Effects of calcitonin gene-related peptide on renal blood flow in the rat

The effects of alpha-rat calcitonin gene-related peptide (alpha-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of alpha-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 +/- 3 mm Hg to a maximal depressor response of 91 +/- 2 mm Hg. During the first three doses of alpha-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 +/- 0.3 ml/min to a peak level of 6.3 +/- 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 +/- 0.2 ml/min (P less than 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of alpha-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of alpha-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 +/- 0.06 to 0.14 +/- 0.5 muEq/min (P less than 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P greater than 0.05) from their respective baselines. These results demonstrate that alpha-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that alpha-rCGRP may have significant effects on the excretory function of the kidney.     

Interaction among atrial natriuretic factor (ANF), vasopressin, and renal nerves in terms of renal responses in rats.

The relationship between the renal nerves and vasopressin in terms of the natriuretic and diuretic responses to atrial natriuretic factor (ANF--0.25 microgram/kg/min for 15 min), was investigated in unilaterally denervated anesthetized rats before and after the administration of a vasopressin V2 specific antagonist (AVPX)--(40 micrograms/kg bolus followed by 0.4 microgram/kg/min infusion). Administration of the AVPX or ANF did not alter the arterial pressure. Acute renal denervation or AVPX administration independently produced significant increases in sodium and water excretion. ANF infusion by itself produced a greater increase in urine flow and sodium excretion from the denervated kidney compared to the intact kidney before the administration of AVPX. However, after the administration of AVPX renal responses to ANF from the intact kidneys were enhanced such that they were not significantly different from the denervated kidneys. These results suggest that the full physiological response to ANF may be masked by tonic renal nerve activity or antidiuretic actions of vasopressin. Furthermore, since combined renal denervation and AVPX administration does not produce any greater potentiation of the renal responses to ANF than either of these manipulations alone, it is suggested that they may act via a common mechanism, possibly altering activity in the renal nerves.     

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy

The present study evaluated the possible role of the renal dopaminergic system in the sodium retention of HgCl2-induced nephrotic syndrome. The time courses of urinary excretion of sodium, protein, dopamine and the precursor l-3,4-dihydroxyphenylalanine (L-Dopa) were evaluated in HgCl2-treated and control rats up to day 21. The renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine, was evaluated during negligible proteinuria accompanied with enhanced sodium retention (day 7), increased proteinuria accompanied with greatest sodium retention (day 14) as well as during increased proteinuria accompanied with negative sodium balance (day 21). Also, the influence of volume expansion (VE, 5% bw) and the effects of the D1-like agonist fenoldopam (10 microg kg bw(-1) min(-1)) on natriuresis and on proximal tubular Na+,K+-ATPase activity were examined on day 14. The daily urinary dopamine output and urinary dopamine/L-Dopa ratios were reduced in HgCl2-treated rats from day 2 and beyond. This was accompanied by a marked decrease in renal AADC throughout the study. During VE, the fenoldopam-induced inhibition of proximal tubular Na+,K+-ATPase activity was similar between HgCl2-treated and control rats. However, the urinary sodium excretion during fenoldopam infusion was markedly increased by 60% to 120% in control rats but was not altered in HgCl2-treated rats. It is concluded that HgCl2 nephrosis is associated with a blunted renal dopaminergic system activity. However, the lack of renal dopamine in HgCl2 nephrosis does not appear to be related with the overall renal sodium retention in a state of proteinuria.     

A stop-flow study of intrarenal effects of atrial natriuretic factor

We performed paired series of stop-flow studies on six mongrel dogs to determine a possible nephron site of action of synthetic atrial natriuretic factor (ANF). The initial free-flow response to intrarenal infusion of 5 micrograms/min of synthetic ANF into mannitol-expanded dogs resulted in an increased urine flow rate (6.81 +/- 0.88 to 9.00 +/- 1.17 ml/min, P less than 0.05) and a 40% increase in sodium excretion (496 +/- 110 to 694 +/- 166 meq/min, P less than 0.025) when compared to paired control periods. Renal blood flow did not change, but the glomerular filtration rate increased 4% (47 +/- 5 to 49 +/- 6 ml/min, P less than 0.05). The filtered load of sodium increased 4% (P less than 0.05), and the fractional sodium excretion increased by 35% (P less than 0.01). Stop-flow experiments showed no difference in tubular sodium concentration or in the fractional sodium-to-inulin ratio at the nadir of sodium concentration, suggesting that no differences existed in distal tubular sodium handling. Further, no apparent differences were detected in collections representing the more proximal portions of the nephron. While we were able to demonstrate marked natriuresis in response to synthetic ANF, no tubular effect was discernible, and the natriuresis obtained appears to be predominantly a function of hemodynamic effects.     

The effect of renal vasodilation and hypotonic volume expansion on water excretion in dogs after anesthesia and surgery

The possible effects of renal vasoconstriction from anesthesia and surgery on water excretion after hypotonic volume expansion (HVE) were studied in 18 well conditioned anesthetized dogs, with and without the infusion of phenoxybenzamine and acetylcholine into the renal artery of the cannulated kidney. In 6 dogs (Group 1 - Control) whose renal artery was infused with isosmotic saline, HVE resulted in a bilateral increase in GFR and UV (p < .05). ERPF, Cosm, C_H2O, U_NaV, U_KV, RBF, RVR and MAP did not change significantly. In 6 other dogs (Group 2), whose cannulated kidney was infused with phenoxybenzamine 50 μg/min before and during HVE, GFR increased on the infused side while CH₂O and UV increased bilaterally (p < .05). ERPF, Cosm, U_NaV, U_KV, RBF, RVR and MAP were not affected significantly. The addition of ADH, 2 mu/min into the phenoxybenzamine infusate, decreased ERPF, RBF and RVR bilaterally and CH₂O on the infused side (p < .05). It had no effect upon GFR, Cosm, U_NaV, U_KV and MAP. In another 6 dogs, (Group 3), whose cannulated renal artery was infused with acetylcholine (20 μg/min) before and during HVE, C_H2O, UV and RVR increased bilaterally (p < .05). ERPF and RBF decreased bilaterally (p < .05), whereas GFR, Cosm, U_NaV and MAP were unaffected. U_KV decreased on the infused side (p < .05). The addition of ADH (2 mu/min)_into the acetylcholine infusate, decreased C_H2O bilaterally and increased Cosm and U_KV on the control side (p < .05). It had no effect on ERPF, GFR, UV, U_NaV, RBF, RVR and MAP. These observations suggest that anesthesia and surgery produce renal vasoconstriction and this together with increased ADH release, interfere with water excretion by the kidney. Previous renal vasodilation prevents these influences of anesthesia and surgery.     

Attenuated renal responses to atrial natriuretic factor in streptozotocin-induced diabetic rats

To determine whether the renal responses to atrial natriuretic factor (ANF) are altered in the diabetic state, the diuretic and natriuretic responses to ANF (0.25 microgram.kg-1.min-1, i.v.) were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Urine flow and sodium excretion were measured before and after ANF from innervated and denervated kidneys in anesthetized (Inactin 0.1 g/kg, i.p.) control and DIA rats (Sprague-Dawley rats injected with vehicle or STZ 65 mg/kg, i.p., respectively, 2 weeks prior to the experiment). Blood glucose levels were significantly elevated in the DIA group compared with the control group. ANF produced a significantly blunted diuresis and natriuresis in DIA rats compared with control rats. In addition, reducing the hyperglycemia in DIA rats by treatment with insulin (third group) reversed the blunted urine flow and sodium excretion responses to ANF. This study demonstrates that (i) there is a blunted natriuresis and diuresis to ANF in the STZ-induced DIA rats, and (ii) restoring the glucose levels to normal by insulin treatment in the DIA rats normalized the renal responses to ANF.     

Atrial natriuretic factor (ANF) increases urinary protein excretion in patients with essential hypertension: a possible role of ANF for renal handling of protein

Low dose iv infusion (0.01 and 0.03 micrograms/kg per min, for 30 min each) of alpha-human atrial natriuretic factor (alpha-hANF) produced a significant increase (+300%) in urinary protein excretion in patients with essential hypertension but not in normotensive controls, when their renal function was normal. The major component of excreted proteins induced by alpha-hANF infusion was presumed to be albumin on the basis of molecular weight (69,000) analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Urine output and sodium and potassium excretion rates were increased dose-dependently by alpha-hANF infusion in the hypertensive patients in a similar fashion to those in the controls. Glomerular filtration rate (GFR) remained unchanged in the controls but was slightly increased in the patients (+33%) during the infusion. These results suggest that besides its previously recognized physiological functions such as natriuresis and diuresis, ANF plays an important role in the regulation of renal handling of proteins in patients with essential hypertension.     

Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate (Ap4A) and nicotinamide adenine dinucleotide (NAD) in rat.

Effects of Ap4A and NAD--precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus--1 micromol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparison with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pretreatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, whereas Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus--12 mg/kg followed by 1.2 mg/min/kg) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product--adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.     

Effect of lysophosphatidylcholine on renal hemodynamics and excretory function in anesthetized rats.

The effect of myristoyl-lysophosphatidylcholine (myristoyl-LPC) on renal hemodynamics, electrolyte and water excretion was examined over a 90 min period in sodium pentobarbital anesthetized male Sprague Dawley rats. Intravenous infusion of myristoyl-LPC at 13 +/- 3 pmol/min resulted in a small fall in systemic blood pressure, a 13% decrease in renal plasma flow without significantly altering glomerular filtration rate and produced a slightly greater excretion of sodium and water than vehicle controls. These results suggest that short term myristoyl-LPC administration can significantly alter renal function producing a weak natriuresis and diuresis which is not dependent on systemic blood pressure and renal hemodynamic changes.