Intrarenal blood flow distribution: effect of carotid occlusion.

In this study we have examined the influence of bilateral carotid occlusion on intrarenal blood flow distribution. Using labeled microspheres to determine intrarenal hemodynamics, bilateral carotid ligation in mannitol or saline expanded dogs resulted in an increase in outer cortical blood flow and a decrease in inner cortical flow. Total renal blood flow and glomerular filtration rate did not change significantly during carotid occlusion whereas the average mean arterial blood pressure rose from 130 to 166 mmHg. Inner cortical flow resistance increased substantially after carotid occlusion; outer cortical resistance was unchanged. These results suggest that bilateral carotid occlusion selectively activates inner cortical renal sympathetic fibers.     

Lack of renal effects of DOCA, ACTH, spironolactone, and angiotensin II in Squalus acanthias

Angiotensin II was infused intravenously in spiny dogfish sharks (Squalus acanthias). There were no significant effects on arterial blood pressure, glomerular filtration rate, urine flow, or Na excretion either in comparison with pre- and postinfusion values or in comparison with values measured in a control group of fish given elasmobranch saline intravenously. In other dogfish, glomerular filtration rate, urine flow, and Na and K excretory rates were measured for 3 days following implantation of desoxycorticosterone (DOCA), adrenocorticotropin (ACTH), or spironolactone; a control group was given no drug. There were no significant differences between these four groups of fish with respect to any of the measured parameters. These results suggest that the dogfish kidney is not a target organ for several substances known to affect renal function, either directly or indirectly, in other animals.     

Early changes in renal function following chemically induced nephropathy

The functional changes in the rat kidney 24 h after administration of 2-bromoethanamine hydrobromide (BEA) have been extensively described. There is, however, little information regarding earlier alterations. The present study was designed to measure early changes in renal function in order to clarify further pathomechanisms of the BEA-induced lesion. Experiments were performed in two groups of Wistar rats with different infusion rates during the first 3 h following injection of 100 mg/kg BW BEA compared to sham-injected rats. Analysis included measuring urine flow, osmolality, urea, sodium and potassium as well as inulin and para-aminohippuric acid clearance. Our studies show a tubular as well as a glomerular involvement in BEA-induced nephropathy. A significantly higher urine flow occurred already in the first 30 min following injection of BEA. Urine osmolality began to decrease after 90 min, Na excretion was elevated at 3 h, K excretion was not significantly different from the control group, urea excretion was increased after 30 min. Contrary to other studies we found a continuously decreasing glomerular filtration rate and PAH clearance during the first 3 h. Our results suggest an early effect of BEA on tubular function (increasing sodium excretion), papillary concentration capacity (increasing urine flow combined with decreasing osmolality) and glomerular function (decreasing glomerular filtration rate).     

Renal effects of an acute NaCl load in chronic nitric oxide blockade-induced hypertensive rats

Nitric oxide (NO) controls blood pressure and plays a role in the water and sodium handling by the kidneys. Inhibition of NO synthesis with competitive L-arginine analogues leads to increased renal vascular resistance and raised systemic and glomerular blood pressure. The effects of chronic NO-synthesis inhibition by N(G)-nitro L-arginine methyl-esther (L-NAME) in the disposal of an acute NaCl load are studied on fourteen male Munich-Wistar rats. Eight of which were given L-NAME (100 mg/L) in the drinking water for 21 days. Six control rats differed only in not receiving L-NAME. As expected, significant hypertension and a marked renal vasoconstriction were accompanied by a decline in renal plasma flow, without changes in glomerular filtration rate, with filtration fraction thus being increased in the NO-blocked rats. In the basal state there was no significant reduction of sodium urinary excretion in the L-NAME treated rats. Both groups of rats elicited an increase in urinary sodium excretion after the NaCl load which was initially more evident and longer in the L-NAME treated group. The ratio of Na+ excreted to Na+ infused was similar between the groups. This observation suggests that in this model of chronic inhibited NO rats, the disposal of an acute sodium load is reached. The existence of a delayed mechanism in renal excretion of Na+ by the chronic NO-blocked rats could be suggested.     

Intrarenal haemodynamics in postobstructive diuresis in the dog

Intrarenal haemodynamics were investigated in the dog prior to and after relief of 24 hr bilateral ureteral ligation (BUL), by the radioactive microsphere technique. Prior to release of 24 hr BUL there was an about 50% reduction in total blood flow (RBR), with a nearly proprotional decrease in the perfusion of the four cortical layers. Following release of the obstruction, total renal and outer cortical (zones 1 and 2) blood flow remained diminished, while perfusion of the inner (juxtamedullary) layers (zones 3 and 4) increased as compared to its prerelease values and equalled controls. Glomerular filtration rate (GFR) amounted to about 27% of controls in the postrelease phase. A marked increase in absolute and fractional sodium water excretion was observed after release of 24 hr BUL, as contrasted to normal controls and dogs after 24 hr unilateral ureteral ligation (UUL). This state, designated as postopstructive diuresis, might be explained by redistribution of intrarenal blood flow towards the juxtamedullary zones, and by a powerful natriuretic substance accumulated during complete obstruction.     

Participation of substance P in the control of renin release.

The effect of the hypothalamic undecapeptide substance P on renin secretion rate was studied in the denervated dog kidney. Intrarenal infusion of substance P at a rate of 0.2 ng/kg/min suppressed renin secretion rates from 258.5 ± 28.5 ng/min to 133.1 ± 23.2 ng/min (p<0.001). Substance P infused at this dose neither changed blood pressure nor did it affect renal cortical plasma flow, glomerular filtration rate or sodium excretion. Thus, the suppression of renin release by substance P cannot be explained by any of the known control mechanisms. It is proposed that substance P participates in the control of renin release by a direct effect on the juxtaglomerular cells.     

Chronic potassium supplementation of newborn dogs increases cortical Na,K-ATPase but not urinary potassium excretion

The distal nephron of the newborn dog cannot secrete an acute potassium load as efficiently as can that of the adult dog. Distal nephron potassium secretion is dependent upon basolateral Na,K-ATPase activity. Because Na,K-ATPase activity is lower in the immature than the mature distal nephron, it was hypothesized that lower Na,K-ATPase activity may be responsible for the lower potassium secretory capacity of the immature nephron. In the adult, chronic high dietary potassium intake increases renal tubular potassium secretory capacity by increasing Na/K pump abundance in distal nephron segments responsible for potassium secretion. Therefore, in order to test the above hypothesis, renal cortical and outer medullary Na,K-ATPase activity under Vmax conditions (a measure of pump abundance) and urinary potassium excretion during acute potassium loading were determined in 7 age-matched, litter mate pairs (chronically potassium supplemented versus control) newborn dogs. The potassium supplemented member of each pair received 6 mmol.day-1.kg-1 of KCl as a 150 mM solution for 7-21 days after birth and the control member received an equal volume of water for the same period of time. This protocol resulted in a doubling of renal cortical Vmax Na,K-ATPase activity in the potassium supplemented animals (from 369 +/- 186 to 718 +/- 286 nmol Pi liberated.h-1.micrograms DNA-1, P = 0.025). There was no significant change in outer medullary enzyme activity. Contrary to the above hypothesis, this increase in cortical enzyme activity was not associated with increased potassium excretion at baseline or during acute potassium loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

A role for the angiotensin IV/AT4 system in mediating natriuresis in the rat

Angiotensin II (AngII) or Angiotensin IV (AngIV) was infused into the renal artery of anesthetized rats while renal cortical blood flow was measured via laser Doppler flowmetry. The infusion of AngII produced a significant elevation in mean arterial pressure (MAP) with an accompanying decrease in cortical blood flow, glomerular filtration rate (GFR), urine volume, and urine sodium excretion. The infusion of AngIV induced significant increases in renal cortical blood flow and urine sodium excretion, without altering MAP, GFR, and urine volume. Pretreatment infusion with a specific AT1 receptor antagonist, DuP 753, blocked or attenuated the subsequent AngII effects, while pretreatment infusion with the specific AT4 receptor antagonist, Divalinal-AngIV, blocked the AngIV effects. These results support distinct and opposite roles for AngII and AngIV, i.e. AngII acts as an anti-natriuretic agent, while AngIV acts as a natriuretic agent.     

Role of antidiuretic hormone in hyponatremia in patients with isolated adrenocorticotropic hormone deficiency.

We found symptomatic hyponatremia in four elderly patients in which serum sodium (Na) levels ranged from 101 to 122 mEq/l. All 4 patients had low levels of plasma adrenocorticotropic hormone (ACTH), serum cortisol, and urinary excretion of 17-OHCS, and poor responses of ACTH to exogenous insulin and antidiuretic hormone (ADH). Other pituitary hormones were all normal. They were therefore diagnosed as having isolated ACTH deficiency. Plasma ADH was relatively high despite hypoosmolality which was associated with the hyponatremia. Water loading test revealed impaired water excretion and poor suppression of plasma ADH. Replacement with 20-30 mg hydrocortisone completely restored the serum Na level and restored the plasma ADH level to the normal range in all 4 patients. Other factors such as decreased glomerular filtration, enhanced urinary Na loss and decreased Na intake were also included. These results indicate that there is marked hyponatremia and that in the presence of hypoosmolality the sustained secretion of ADH is the key factor in causing the impaired water excretion and hyponatremia in isolated ACTH deficiency.     

Cardiac edema in dogs: distribution of renal blood flow and glomerular filtrate.

The injection of Freund's adjuvant into the pericardial sac of 29 dogs resulted in chronic pericardial tamponade with persistent sodium retention. Micropuncture, clearance, and radioactive microsphere experiments were initiated 6--13 days after pericardial injection and 60 min after pericardiocentesis. Pericardiocentesis increased sodium excretion (from 12.2 to 41.3 microequiv./min) and mean arterial pressure (+ 20 mmHg (1 mmHg = 133.322 Pa)). Central venous pressure decreased 6.5 mmHg, as did hematocrit (from 45.7 to 39.8%) and plasma protein concentration (from 5.88 to 5.15 g%). Pericardiocentesis had no significant effect on renal blood flow (RBF), nor plasma flow. Redistribution of glomerular filtrate was suggested by the observation that superficial nephron glomerular filtration rate increased (from 91 to 108 nL/min) while glomerular filtration rate remained unaltered. Determination of intrarenal distribution of RBF revealed that cortical blood flow also distributed superficially. A significant increase in the fraction of RBF perfusing zone 1 (outer cortex) and a decrease in fractional perfusion of zones 2, 3 and 4 (juxtamedullary cortex) were observed in each experiment following pericardiocentesis. RBF distribution examined in a series of six animals prior to and during the development of pericardial tamponade showed the opposite effect. These results indicate that pericardiocentesis causes redistribution of both glomerular filtrate and RBF to superficial nephrons. The development of pericardial tamponade was associated with increased fractional juxtamedullary blood flow. These changes may have been the result of altered blood pressure, hematocrit, plasma protein concentration, or altered renal resistance.     

Antidiuretic action of prolactin in the rat with diabetes insipidus.

Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and insulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis.     

Diuretic actions of 1-((tert-butylimino)methyl)-2-(3-indolyl) indoline HCl (MJ 8592-1) in adrenalectomized or ADH-primed rats

MJ 8592-1, an orally active diuretic indolylindoline derivative, effectively reversed the relative oliguria induced by ADH (Pitressin®) in ethanol-saline primed intact rats. It was 5.5, .96 and >18 times as potent, respectively, as furosemide, HCTZ and triamterene in producing a 100% increase in Na excretion in the presence of ADH. Since MJ 8592-1 also elicited a diuretic-saluretic response in ethanolsaline primed rats in the absence of ADH, the antagonism to exogenous vasopressin may be classified as non-specific. In adrenalectomized rats, MJ 8592-1, like triamterene, produced dose-related electrolyte excretion responses in both the presence and absence of exogenous DOCA. Thus, while MJ 8592-1 was effective in counteracting mineralocorticoid-induced Na retention in the distal tubule, it was also capable of increasing Na excretion by a mechanism independent of any direct interactions with adrenal cortical steroids or tubular sites influenced by these hormones.     

垂体在刺激脑内渗透压感受器引起的肾脏反应中的作用

实验在α氯醛糖和氨基甲酸乙酯混合麻醉的大鼠中进行。脑室内注射高张盐水(icv.HS)后,肾血浆流量、肾小球滤过率、尿量、尿钠排出量、尿钾排出量和渗透物质清除率均增加,游离水清除率下降。去除垂体后,icv.HS不再能引起上述肾脏反应。另外给大鼠静脉注射血管升压素(VP)拮抗剂(V_1和V_2受体拮抗剂),并不能削弱上述icv.HS引起的肾脏反应。脑室内注射高张盐水后,尿中多巴胺(DA)排出量无显著增多;给予多巴脱羧酶抑制剂苄丝肼也不能削弱icv.HS引起的肾脏反应。上述实验结果表明,在本实验条件下刺激脑内渗透压感受器引起的肾脏反应依赖于垂体的完整性,但看来并不依赖于外周的VP和DA,故垂体通过何种机制介导icv.HS引起上述肾脏反应,有待于进一步的研究。     

Changes in electrolyte excretion following intraperitoneal injection of dibutyryl cyclic AMP in the brattleboro rat

Intraperitoneal injection of 40 μg of dibutyryl cyclic AMP to homozygous Brattleboro rats fasted for 12 hours but having free access to water resulted in an increase in urine flow and in the rates of excretion of Na, K, PO₄ and urea. Similar results were obtained in Brattleboro rats having free access to food and water which received 200 μg of nucleotide. The injection of 20 μg of dibutyryl cyclic AMP or 40 μg 5′-AMP to homozygous Brattleboro rats with free access to food and water or the administration of 40 μg of 5′-AMP to homozygous rats fasted for 12 hours but with free access to water did not alter renal excretion patterns. These results indicate that dibutyryl cyclic AMP may depress tubular reabsorption of water, Na and PO₄ as has been shown to be the case in the intact dog.In homozygous Brattleboro rats fasted for 24 hours but allowed free access to water, 40 μg of dibutyryl cyclic AMP resulted in a tendency to reduced urine flow and diminished excretion of Na, K and urea. The explanation for these results is not apparent from these data.     

Acceleration of p-aminohippurate excretion in immature rats by dexamethasone treatment

In 5-, 10- and 15-day-old rats repeated administration of dexamethasone caused a dose-dependent increase of p-aminohippurate (PAH) excretion. Remarkably, dexamethasone has no influence on PAH excretion in adult rats. The effect of treatment in young rats cannot be explained by an increase in the glomerular filtration rate. In 10-day-old rats GFR shows a tendency to increase. In renal cortical slices from 5-day-old rats PAH transport is increased following dexamethasone treatment, whereas in 10- and 15-day-old rats an increase of kidney mass seems to be responsible for acceleration of renal excretion of PAH after administration of dexamethasone. In 5-day-old rats only the protein content is statistically significantly increased after dexamethasone treatment.     

Head-down tilt and restraint on renal function and glomerular dynamics in the rat

A model utilizing 25 degree head-down tilt (HDT) and incorporated with chronic catheterization and renal micropuncture techniques in rats was employed to study alterations in renal function induced by HDT. Renal function and extracellular volume measurements were performed after 24 h, 4 days, and 7 days of HDT in conscious rats and compared with their own control measurements and to nontilted but similarly restrained rats. After 24 h HDT, glomerular filtration rate (GFR) increased 19 +/- 8% and renal plasma flow (RPF) increased 18 +/- 8% with increases in urine flow rate, Na+, and K+ excretion in conscious rats. These increases after 24 h were associated with an increase in extracellular volume of 16 +/- 3% (P less than 0.01). In the nontilted controls, there was a decrease in extracellular volume after 24 h of suspension. After 7 days of HDT, GFR was decreased by 7 +/- 1% (P less than 0.01), but RPF and extracellular fluid volume were not different from control values. However, RPF and GFR increased in the nontilted rats after 7 days. After 7 days of HDT renal micropuncture studies demonstrated that single-nephron filtration rate was also decreased from 43 +/- 2 to 31 +/- 3 nl/min (P less than 0.05) due solely to reductions in the glomerular ultrafiltration coefficient (0.11 +/- 0.01 to 0.07 +/- 0.01 nl.s-1 X mmHg-1, P less than 0.05). There was a dissociation between GFR and water and Na+ excretion at days 4 and 7 of HDT not observed in the nontilt restraint controls.     

Studies on the mechanism of non-oliguric experimental acute renal failure.

Although acute renal failure, caused either by renal ischemia or nephrotoxic agents, is usually characterized by oliguria, a severe fall in glomerular filtration rate, and a fall in renal blood flow, some patients and experimental models display a non-oliguric pattern of renal injury. The present study was designed to evaluate the mechanism of preservation of high urinary flow rate under this condition. Following the administration of the aminoglycoside gentamicin to rats for five days, a decrease in concentrating ability was demonstrated, caused by impaired vasopressin-mediated water transport. Further treatment resulted in a fall in Cin to 15 percent of control, although RBF was reduced to only 67 percent of control, and urine flow rate rose above control levels. Induction of acute and renal failure with dichromate was associated with variable high or low urinary flow rates according to pre-injury intake of sodium. Urine volume correlated directly with cortical blood flow. These data suggest that the non-oliguric pattern of acute renal injury is caused by preservation of cortical perfusion in the setting of severe tubular injury.     

Involvement of Rho kinase pathway in the mechanism of renal vasoconstriction and cardiac hypertrophy in rats with experimental heart failure

Rho-dependent kinases serve as downstream effectors of several vasoconstrictor systems, the activities of which are upregulated in congestive heart failure (CHF). We evaluated renal and cardiac effects of Y-27632, a highly selective Rho kinase inhibitor, in an experimental model of volume-overload CHF. Effects of acute administration of Y-27632 (0.3 mg/kg) on renal hemodynamic and clearance parameters and effects of chronic treatment (10.0 mg.kg(-1).day(-1) for 7 days via osmotic minipumps) on cardiac hypertrophy and cumulative Na+ excretion were studied in male Wistar rats with aortocaval fistula and control rats. The Y-27632-induced decrease in renal vascular resistance (from 40.4 +/- 4.6 to 26.0 +/- 3.1 resistance units, P < 0.01) in CHF rats was associated with a significant increase in total renal blood flow (+34%) and cortical and medullary blood flow (approx +37 and +27%, respectively). These values were significantly higher than those in control rats and occurred despite a decrease in mean arterial pressure (-15 mmHg). Despite the marked renal vasodilatory effect, Y-27632 did not alter glomerular filtration rate and renal Na+ excretion. Chronic administration of Y-27632 did not alter daily or cumulative renal Na+ excretion in CHF rats but was associated with a significant decrease in heart-to-body weight ratio, an index of cardiac hypertrophy: 0.32 +/- 0.007, 0.46 +/- 0.017, and 0.37 +/- 0.006% in control, CHF, and CHF + Y-27632 rats, respectively. The findings suggest that Rho kinase-dependent pathways are involved in the mechanisms of renal vasoconstriction and cardiac hypertrophy in rats with volume-overload heart failure. Selective blockade of these signaling pathways may be considered an additional tool to improve renal perfusion and attenuate cardiac hypertrophy in heart failure.     

The effects of two analogues of arginine-vasopressin (ornithine-vasopressin and desamino-D-arginine-vasopressin) on kidney function in sheep.

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-arginine-vasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction. These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone. The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.     

Furosemide, indomethacin and sodium excretion in isolated, blood-perfused dog kidneys

Sodium excretion, renal blood flow and glomerular filtration rate were investigated in isolated, blood-perfused dog kidneys, thus excluding the interference of changes in body sodium and water balance. Four groups of experiments were performed : (a) control; (b) blood + indomethacin; (c) blood + furosemide; (d) blood + furosemide and indomethacin. The progressive vasodilatation due to the accumulation of prostaglandins was suppressed by indomethacin, the glomerular filtration rate remaining unchanged. The inhibition of prostaglandins synthesis was without influence on the natriuretic activity of furosemide. These results seem incompatible with an intrarenal mediation by prostaglandins of the diuretic effect of furosemide; moreover, this effect was dissociated from the changes in renal blood flow ascribed to renal prostaglandins.