BACKGROUND: K+ channel opener has been considered as a vasorelaxing agent working through hyperpolarization of vascular smooth muscle cells. Renal tubules-proximal, thick ascending limb of Henle and cortical collecting duct-are the site of the diversity of the K+ channel. ATP-sensitive K+ channel has been observed in the apical membranes of the thick ascending limb of Henle and collecting duct, and basolateral membrane of the proximal tubule. It was also shown that K+ channel opener increased renal hemodynamics and elicited diuretic and natriuretic effects. METHODS: To clarify the renal effects of WAY120491, a K+ channel opener, experiments were performed in unanesthetized normotensive and renal hypertensive rabbits allowing unilateral renal arterial infusion of agent. RESULTS: Intrarenal arterial infusion (0.13, 0.32 and 0.64 microgram/kg/min) of WAY120491 increaased CPAH, CCr, urine volume, UNaV, UKV and CH2O. Renal hemodynamic effects and increments of urine volume and free water clearance were completely blocked by glibenclamide (8.2 g/kg/min), while increments of UNaV and FENa were not significantly affected. Renal hemodynamic and tubular effects of WAY120491 were not significantly different in two-kidney one clip Goldblatt hypertensive rabbits from sham-operated rabbits. CONCLUSIONS: These results suggest that WAY120491 elicits renal effects through ATP-sensitive K+ channel in the renal vasculatures and renal tubules and the renal effects of WAT120491 may not be altered in the hypertension.
Diuresis ; Extremities ; Glyburide ; Hemodynamics ; Hypertension ; Membranes ; Muscle, Smooth, Vascular ; Natriuresis ; Natriuretic Agents ; Rabbits* ; Water

Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT-1 (5-hydroxytryptamine-1) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT-2 and 5-HT-3 receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT-1A subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT-1A receptors. PAPP in doses ranging from 40 to 350 microgram/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption (T-cH-2O), a measure of ADH (antidiuretic hormone) secretion, was increased also. Intravenous 350 microgram/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT-2 antagonist, 40 microgram/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT-1 antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT-1A antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT-1A receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.
Blood Pressure ; Diuresis ; Filtration ; Ketanserin ; Kidney ; Methysergide ; Natriuresis ; Perfusion ; Rabbits* ; Water

To elucidate the mechanism of gentamicin induced renal dysfunction, renal functions and activities of various proximal tubular transport systems were studied in gentamicin-treated rats (Fisher 344). Gentamicin nephrotoxicity was induced by injecting gentamicin sulfate subcutaneously at a dose of 100 mg/kg cntdot day for 7 days. The gentamicin injection resulted in a marked polyuria, hyposthenuria, proteinuria, glycosuria, aminoaciduria, phosphaturia, natriuresis, and kaliuresis, characteristics of aminoglycoside nephropathy. Such renal functional changes occurred in the face of reduced GFR, thus tubular transport functions appeared to be impaired. The polyuria and hyposthenuria were partly associated with a mild osmotic diuresis, but mostly attributed to a reduction in free water reabsorption. In renal cortical brush-border membrane vesicles isolated from gentamicin-treated rats, the Na+ gradient dependent transport of glucose, alanine, phosphate and succinate was significantly attenuated with no changes in Na+/-independent transport and the membrane permeability to Na+. These results indicate that gentamicin treatment induces a defect in free water reabsorption in the distal nephron and impairs various Na+/-cotransport systems in the proximal tubular brush-border membranes, leading to polyuria, hyposthenuria, and increased urinary excretion of Na+ and other solutes.
Alanine ; Animals ; Diuresis ; Gentamicins ; Glucose ; Glycosuria ; Hypophosphatemia, Familial ; Membranes ; Natriuresis ; Nephrons ; Permeability ; Polyuria ; Proteinuria ; Rats* ; Succinic Acid ; Water

No abstract available.
Anesthesia, Epidural* ; Diuresis*

No abstract available.
Diuresis* ; Humans ; Infant, Newborn*

Nitric oxide has been implicated in many physiologic processes that influence both acute and long-term control of kidney function. Its net effect in the kidney is to promote natriuresis and diuresis, contributing to adaptation to variations of dietary salt intake and maintenance of normal blood pressure. A pretreatment with nitric oxide donors or L-arginine may prevent the ischemic acute renal injury. In chronic kidney diseases, the systolic blood pressure is correlated with the plasma level of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. A reduced production and biological action of nitric oxide is associated with an elevation of arterial pressure, and conversely, an exaggerated activity may represent a compensatory mechanism to mitigate the hypertension.
Acute Kidney Injury ; Arginine ; Arterial Pressure ; Blood Pressure ; Diuresis ; Hypertension ; Kidney ; Natriuresis ; Nitric Oxide ; Nitric Oxide Donors ; Nitric Oxide Synthase ; Plasma ; Renal Insufficiency, Chronic

Adrenomedullin (AM) is a multi-functional peptide discovered in human pheochromocytoma. Initially, it was suggested that AM was synthesized only by tumor cells, however, subsequent studies revealed that it was produced also by normal adrenal medulla as well as by many other tissues. Now it is well established that AM functions as a circulating hormone and local paracrine mediator with multiple biological activities. AM stimulated cAMP production in human platelets and exerted potent and long-lasting hypotensive activity in the rat. AM is a physiologically relevant regulator in fluid and electrolyte homeostasis; inhibition both water and salt intake, increase renal blood flow, and cause diuresis and natriuresis. The up-regulation of cardiac AM system in hypertension may be a protective mechanism decreasing myocardial overload due to vasodilatory and natriuretic properties of AM, as well as limiting further myocardial hypertrophy and remodeling. AM may protect the kidney against ischemia-reperfusion injury. AM is also suggested as antiapoptotic, anti-inflammatory and angiogenic factor. In this review, I offer a review of our current knowledge on AM and give the putative role of AM in water-electrolyte balance, hypertension and kidney disease.
Adrenal Medulla ; Adrenomedullin* ; Angiogenesis Inducing Agents ; Animals ; Diuresis ; Homeostasis ; Humans ; Hypertension ; Hypertrophy ; Kidney Diseases ; Kidney* ; Natriuresis ; Pheochromocytoma ; Rats ; Renal Circulation ; Reperfusion Injury ; Up-Regulation ; Water-Electrolyte Balance

PURPOSE: The present study was aimed to examine whether caffeine alters the local regulation of atrial natriuretic peptide(ANP) and nitric oxide(NO) systems in the kidney. METHODS: Male Sprague-Dawley rats were treated with caffeine, consisting of a single oral bolus(0.2%, 1 mL/kg) followed by supplementation in drinking water(0.2%) for 1 day. Rats treated the same without caffeine served as control. The tissue expression of ANP mRNA was determined by reverse transcription-polymerase chain reaction. Tissue levels of nitrite/nitrate were determined. The expression of aquaporin(AQP)-1 and AQP2 proteins was determined by Western blot analysis. RESULTS: Following the treatment with caffeine, the expression of ANP mRNA was increased in the kidney. The renal tissue nitrite/nitrate level was also increased by caffeine-treatment. On the other hand, the expression of AQP1 and AQP2 proteins was not significantly altered. CONCLUSION: The enhanced activities of local ANP and NO systems may in part be causally related with the caffeine-induced natriuresis and diuresis, while AQP channels are not involved.
Animals ; Aquaporin 2 ; Atrial Natriuretic Factor ; Blotting, Western ; Caffeine* ; Diuresis ; Drinking ; Hand ; Humans ; Kidney ; Male ; Natriuresis ; Nitric Oxide* ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger

Although the obstruction is potentially reversible with treatment, marked and sometimes prolonged diuresis and natriuresis associated with an impaired ability to concentrate the urine may follow relief of the obstruction. Various factors contributing to the postobstructive diuresis and natriuresis have been suggested, including decreases of tubular sodium reabsorption, retention of urea and expansion of extracellular fluid volume. Tubular damage as a consequence of obstruction may occur one or more nephron segments and may result in decreased reabsorption of filtrate. The discovery of aquaporin (AQP) membrane water channels and sodium (co)transporters and channels provided insight, at the molecular level, into the fundamental physiology and pathophysiology of water and sodium balance. In addition, recent studies have shown that the kidney per se is also a site of production and release of atrial natriuretic peptide (ANP). The locally synthesized ANP may act in a paracrine manner to increase the urinary excretion of sodium and water. In this context, an altered regulation of ANP in the kidney may result in an altered urinary excretion. The combined interactions of multiple independent mechanisms are thought to be involved in the pathogenesis of postobstructive diuresis and natriuresis. We examined the changes of AQP water channels, sodium (co)transporters and natriuretic peptide system in obstructed kidneys. The expression of AQP water channels and sodium transporters was decreased in the obstructed kidneys, which may at least in part account for the urinary concentration defect associated with postobstructive diuresis and natriuresis. In addition, the postobstructive natriuresis was associated with an enhanced renal expression of ANP mRNA and an increased urinary excretion of ANP. The plasma dendroaspis natriuretic peptide (DNP) level was increased following an experimental ureteral obstruction. The urinary excretion of DNP was increased along with the postobstructive diuresis. An enhanced activity of DNP system may in part play a role in mediating the postobstructive diuresis
Animals ; Aquaporins* ; Atrial Natriuretic Factor ; Diuresis* ; Elapidae ; Extracellular Fluid ; Kidney* ; Membranes ; Natriuresis ; Natriuretic Peptides ; Negotiating ; Nephrons ; Physiology ; Plasma ; Rats* ; RNA, Messenger ; Sodium* ; Urea ; Ureteral Obstruction

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.
Atrial Natriuretic Factor ; Blood Pressure ; Brain ; Central Nervous System ; Diuresis ; Filtration ; Hemodynamics ; Hypotension ; Kallidin* ; Kallikreins* ; Natriuresis ; Natriuretic Agents ; Neurotransmitter Agents ; Plasma ; Renal Circulation ; Sodium ; Water