• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.98-98
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• 2001

It has been suggested that hyperuricemia is related to the development of essential hypertension. Hypertensive patients with hyperuricemia has decreased glomerular filtration activity as compared to normotensive patients with hyperuricemia. These studies indicates uric acid concentrations in blood is associated with hypertension, Probenecid is an uricosuric agent which decreases uric acid reabsorption at the proximal tubule. Recently, we have shown that probenecid exerts anti-hypertensive action in Spontaneously Hypertensive Rats. Considering these results, I have designed a series of experiments to explore potential mechanism of antihypertensive action, of probenecid. In isolated rat thoracic aorta. probenecid significantly prevented phenylephrine-induced contraction of the blood vessel. When endothelium removed blood vessels were used, probenecid produced same effect as the intact blood vessels, indicating that probenecid directly act through the ${\alpha}$ -adrenergic receptor in vascular smooth muscles rather than through endothelium. These results suggest that one of the mechanism of antihypertensive effects of probenecid is due to the direct inhibition of ${\alpha}$ -adrenergic receptor in blood vessels.

• 약학회지
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• 제39권3호
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• pp.314-328
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• 1995

This study was attempted to investigate the mechanism of retention of sodium and water by naproxen which is a drug among nonsteroidal anti-inflammatory drugs in dogs. Napoxen, when given intravenously in doses ranging from 30 mg to 100 mg/kg, elicited antidiuresis accompanied vath the decrease of osmolar clearance(Cosm) and amounts of sodium excreted in urine(E$_{Na}$), with the increase of sodium reabsorption rate in renal tubule(R$_{Na}$) and ratio of potassium against sodium (K/Na). Naproxen infused into a renal artery in doses ranging from 1.0mg to 3.0mg/kg/min produced both diuretic action in infused kidney and antidiuretic action in control kidney. Naproxen injected into carotid artery in doses ranging from 10.0 mg to 30.0 mg/kg exhibited antidiuretic action. Changes of renal function in the circumstances of above two antidiuresis were the same with aspect of intravenous naproxen. Antidiuretic action of naproxen injected into carotid artery was not affected by renal denervation, was blocked by pretreatment with i.v. arachidonic acid, prostaglandin precursor, or i.v. indomethacin, cyclooxygenase inhibitor. Naproxen injected into carotid artery abolished the diuretic action of i.v. spironolactone, aldosterone antagonist, and i.v. spironolactone blocked the antidiuretic action of naproxen given into carotid artery. The results suggest that naproxen produced antidiuresis, and sodium and water retention through the central system, the mechanism being related to the prostaglandin biosynthetic inhibition and aldostercfne like action.

• 대한약리학회지
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• 제12권2호
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• pp.43-49
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• 1976

The facts that $PGE_2$ produced diuresis in the rabbit when given into a lateral ventricle of the brain and that $PGF_{2{\alpha}}$ is abundantly found in the brain prompted us to investigate the effects of $PGF_{2{\alpha}}$ introduced directly into the ventricle on the renal function. $PGF_{2{\alpha}}$ given intraventriculary in doses of $10{\mu}g\;and\;100{\mu}g$ elicited prompt diuresis, 10-fold increase of sodium excretion and two-fold increment of potassium excretion. Free water reabsorption also increased along with the increased osmolar clearance. Neither renal plasma flow nor glomerular filtration rate did change significantly. This, along with the fact that the percentage of reabsorbed sodium filtered decreased from 99.5 to 93.9, indicates the tubular site of the diuretic and natriuretic action. Atropine pretreatment did not influence the renal effects of intraventricular $PGF_{2{\alpha}}$. Intravenously administered $PGF_{2{\alpha}}$ in doses of 30 to $100{\mu}g$ did not produce any significant change in renal function. Intraventricular $PGF_{2{\alpha}}$ had no effect on the systemic blood pressure, whereas intravenous administration brought about a transient hypotension. These observations suggest that $PGF_{2{\alpha}}$ induces diuresis and natriuresis via central mechanism, that the site of the action resides in renal tubules, and that the reabsorption of sodium is inhibited in the proximal tubule, possibly through mediation of certain humoral agent. Overall, it is suggested that $PGF_{2{\alpha}}$ might play a roll in regulating renal function through the center.

• 대한약리학회지
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• 제7권1호
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• pp.67-76
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• 1971

The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

• 약학회지
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• 제33권3호
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• pp.183-190
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• 1989

Angiotensin II, adminstered (infused or injected) intravenously, elicited the antidiuretic action with the decreased parameters of renal function at a small dose ($0.01\;{\mu}g/kg/min$), whereas, at a large dose (0.03, $0.1\;{\mu}g/kg/min$ and $5.0\;{\mu}g/kg$), it produced the diuretic action accompanied the increased amounts of sodium and potassium excreted in urine ($E_{Na}\;and\;R_K$). At this time, glomerular filtration rates (GFR) were weakened slightly and renal plasma flows (RPF) were reduced markedly, and then filtration fractions (FF) were increased. Angiotensin II, infused into a renal artery, exhibited antidiuretic action at a small dose ($0.003\;{\mu}g/kg/min$), and diuretic action at a large dose ($0.01\;{\mu}g/kg/min$), only in infused (experimental) kidney. The mechanism of the action was similar to the cases of the intravenous angiotensin II. The above results suggest that angiotensin II of a large dose produced diuretic action due to mechanism inhibiting reabsorption of electrolytes in renal tubules, mainly in proximal tubule in dog.

• 약학회지
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• 제29권3호
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• pp.130-143
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• 1985

Bumetanide, when given intravenously in dogs, induced a potent diuresis with an increased amounts of sodium and potassium excreted in urine due to inhibition of reabsorbing them in renal tubule. Furthermore, clearances of osmolar substance and para-aminohippuric acid were increased, but clearace of free water diminished without any change of creatinine clearance. Bumetanide, administered directly into a renal artery, elicited diuresis only in the infused(experimental) kidney by the same mode of action as in the intravenous cases in renal function of the dog. Renal effects of intravenous bumetanide after pretreatment with the small dose of indomethacin (5.0mg/kg) revealed reduction only in clearance of paraaminohippuric acid. However the much dose of indomethacin (5.0mg/kg+5.0mg/kg/hr) or arachidonic acid showed a significant inhibition in the change rates of all renal function by bumetanide. Morover, pretreatment of probenecid also made a marked reduction in renal effects induced by bumetanide. From the above results, it is thought that bumetanide causes diuretic action due to dual mechanism inhibiting reabsorption of electrolytes in loop of Henle and increasing blood flow in kindney, that are provoked through the mediation of prostaglandins.

• Clinical and Experimental Pediatrics
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• 제50권5호
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• pp.430-435
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• 2007

Even though we drink and excrete water without recognition, the amount and the composition of body fluid remain constant everyday. Maintenance of a normal osmolality is under the control of water balance which is regulated by vasopressin despite sodium concentration is the dominant determinant of plasma osmolality. The increased plasma osmolality (hypernatremia) can be normalized by the concentration of urine, which is the other way of gaining free water than drinking water, while the low plasma osmolality (hyponatremia) can be normalized by the dilution of urine which is the only regulated way of free water excretion. On the other hand, volume status depends on the control of sodium balance which is regulated mainly by renin-angiotensin-aldosterone system, through which volume depletion can be restored by enhancing sodium retention and concomitant water reabsorption. This review focuses on the urine concentration and dilution mechanism mediated by vasopressin and the associated disorders; diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion.

• 대한약리학회지
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• 제5권1호
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• pp.57-64
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• 1969

Acetylsalicylic acid, administered intravenously in a dose of 120 mg+250 mg/h, markedly decreased the urinary excretion of sodium and chloride, and slightly depressed potassium excretion, so that the ratio of urinary concentrations of potassium to sodium increased after ASA. Osmolar and free water clearances also diminished during water diuresis, and free water reabsorption $(T^cH_2O)$ decreased after ASA during mannitol diuresis. Glomerular filtration rate and urine flow rate changed little. When infused directly into a renal artery, ASA exhibited identical action on both kidneys, indicating that the renotropic action is mediated by some endogenous humoral agents or by some metabolites of ASA. A dose of 100 mg i.v. of spironolactone, a aldosterone antagonist, slightly reversed the renal reflect when given during maximum action of ASA. Ethacrynic acid could display its full diuretic action unhindered during maximum ASA action. Above observations lead to the suggestion that acetylsalicylic acid might release aldosterone and the action on electrolyte excretion may be mediated by the mineralocorticoid.

• Asian-Australasian Journal of Animal Sciences
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• 제21권8호
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• pp.1178-1182
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• 2008

The present study was designed to assess the influence of caeca on the availability of calcium, phosphorus, magnesium, manganese and copper from soybean, sunflower, rapeseed, sesame, fish and meat cum bone meal in adult roosters. The excretion of endogenous origin minerals viz., copper, magnesium, manganese and calcium was significantly (p<0.001) higher in caecectomized than in normal roosters. The difference in the endogenous excretion was 50; 60.45; 40.35 and 29.63 per cent for copper, magnesium, manganese and calcium, respectively, in caecectomized roosters. The caeca played a pivotal role in the reabsorption of endogenous origin calcium, magnesium, manganese and copper. The mechanism of phosphorus absorption by the caecal epithelium was negligible. The caecectomized roosters underestimated the bioavailability of copper in sunflower meal and manganese in almost all the test feedstuffs. The present investigation revealed that the caeca played a critical role in the absorption of minerals from vegetable protein feedstuffs which escape digestion and absorption in the small and large intestinal segments.

• Journal of Pharmaceutical Investigation
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• 제14권2호
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• pp.92-103
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• 1984

The action of debrisoquine on renal function in rabbits was studied. 1. When debrisoquine was given into ear vein, it did not affect on renal functin with smaller doses of 0.1 or 0.3mg/kg, while with higher dose of 1.0mg/kg it elicited the significant decrease of urine flow, renal plasma flow and glomerular filtration rate, and the increase of filtration fraction, and at the same time sodium excreted in urine, FENa (fractional excretion of sodium) and osmolar clearance were significantly decreased, and then it exhibited the increase of $K^+/Na^+$ ratio and no changes of $T^cH_2O$. 2. Debrisoquine (1.0mg/kg), when injected repeatedly into a vein, produced a more marked decrease of urine flow. 3. Debrisoquine induced-antidiuretic action was not affected by pretreatment with phentolamine (2mg/kg, i.v.), alpha-sympathetic blocking agent. 4. Debrisoquine given intracerebroventricularly did not produce a significant change on renal function in dose of 0.1mg/kg. These results suggest that debrisoquine produce the antidiuretic effect in rabbit, and the mechanism of its action is due to dual actions that are the decrease of hemodynamic effect and the facilitation of reabsorption of sodium in renal tubules.