• The Korean Journal of Physiology
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• v.24 no.1
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• pp.145-159
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• 1990

Recently, it has been suggested that the endogenous adenosine may be the mediator for the intercellular communication in the regulation of tubuloglomerular feedback control and renin release. Even though two subclasses of adenosine receptors, A1 and A2, have been described, their functional roles are controversial. The present study was undertaken to clarify the role of adenosine receptors in hypertensive rabbit caused by clamping of renal artery. Experiments were done in two-kidney one clip Goldblatt hypertensive rabbits (2K1GHR) and sham-operated normotensive rabbits. Adenosine, N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamidoadenosine (NECA) were infused into a renal artery. The decreases in urine volume, renal blood flow, glomerular filtration rate and excreted amounts of electrolytes caused by adenosine and CHA were significantly attenuated in 2K1CHR. However, changes in renal function caused by A2 adenosine receptor agonist, NECA, tend to be accentuated in 2K1CHR. These results suggest that the attenuation of renal effect caused by adenosine and A1 adenosine receptor agonist may be due to the modification of adenosine receptor in the kidney in Goldblatt hypertensive rabbits.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.153-160
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• 1990

5-Hydroxytryptamine (5-HT) was reported to elicit natriuresis and diuresis when given intracerebroventricularly (icv) and these effects were shown to be abolished by icv methysergide, $5-HT{_1}$ antagonist, thus suggesting that central tryptaminergic system may also participate in the regulation of renal function. We tried in this study to elucidate the role of $5-HT_2$ receptors in the central tryptaminergic regulation of renal function, observing the effects of icv ketanserin, a specific $5-HT_2$ antagonist. Ketanserin (KET) icv in doses of $120{\mu}g$ $(=0.3\;{\mu}moles)/kg$ produced significant natriuresis without affecting renal hemodynamics, indicating that it resulted from decreased tubular Na reabsorption. Systemic blood pressure decreased slightly but significantly. When given iv, no significant effect was observed. 5-HT, $200{\mu}g/kg$ icv, produced mild but significant natriuresis and diuresis. However, after KET, $40{\mu}\;g/kg$ icv, a dose which minimally affects renal function, the natriuresis and diuresis by 5-HT was greatly augmented, with the fractional excretion of filtered sodium reaching 9.3%. The renal effects of other biogenic amines administered icv, such as norepinephrine, dopamine and histamine, were not significantly affected by the KET pretreatment. These observations suggest that central tryptaminergic system influences renal function in dual ways, i.e., natriuretic and diuretic influence via $5-HT_1$ receptors, whereas $5-HT_2$ subtypes mediate the antinatriuretic and antidiuretic effects, and that the central tryptaminergic system plays a role in the regulation of rabbit renal function.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.1-10
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• 1982

In an attempt to delineate the role of beta-adrenoceptors found to be existing in the brain tissue in the central regulation of renal function, isoproterenol, a ${\beta}-adrenergic$ agonist, was administered directly into a lateral ventricle of the rabbit brain and the changes of renal function were observed. Also, the effects of propranolol, a specific ${\beta}-adrenergic$ blocking agent, and its influence upon the isoproterenol action were studied. Isoproterenol, in doses ranging from 5 to $50\;{\mu}g/kg\;i.c.v.$, elicited antidiuresis which seemed to be related to the decreased renal hemodynamics brought about by the systemic hypotension. With moderate doaes of $15\;{\mu}g/kg$ the antidiuresis was less prominent and there was a tendency toward natriuresis, but with higher doses the natriuretic effect became less evident, overrun by the systemic hypotension. Propranolol, $500\;{\mu}g/kg\;i.c.v.$, produced little effect on the renal function, but it eliminated the antidiuretic action of $50\;{\mu}g/kg$ isoproterenol i.c.v. and reversed it to a diuretic and natriuretic one, along with increases in renal plasma flow and glomerular filtration rate. The systemic hypotension also was markedly attenuated by propranolol pretreatment. Thus, it was evident that the renal action of i.c.v. isoproterenol was not blocked by propranolol and became explicit only when the hypotensive action of isoproterenol which seems to he propranolol-sensitive is removed. Various possibilities to account for this disparity in sensitivity were discussed. It is suggested from these observations that the central ${\beta}-adrenoceptors$ might also be involved in the regulation of renal function along with ${\alpha}-adrenoceptors$, though less significant than the latter.

• The Korean Journal of Nuclear Medicine
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• v.8 no.1_2
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• pp.1-11
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• 1974

The author in an attempt to evaluate hemodynamic changes in the clinical stages of Korean hemorrhagic fever measured plasma volume, cardiac output and effective renal plasma flow utilizing radioisoto es during various phases of the disease. Cardiac output was measured by radiocardiography with external monitoring method using RIHSA. Effective renal plasma flow was obtained from blood clearance curve drawn by external monitoring after radiohippuran injection according to the method described by Razzak et al. The study was carried out in thirty-eight cases of Korean hemorrhagic fever and the following conclusions were obtained. 1. Plasma volume was increased in the patients during the oliguric-and hypertensive diuretic phases, while it was normal in the patients during the normotensive-diuretic phase. 2. Cardiac index was increased in the patients during the oliguric phase and was slightly increased in the patients at the hypertensive diuretic phase. It was normal in the other phases. 3. Total peripheral resistance was increased in the hypertensive patients during diuretic phase, while it was normal in the rest of phases. 4. Effective renal plasma flow was significantly reduced in the patients during the oliguric and diuretic phases as well as at one month after the oliguric onset. There was no significant difference between the oliguric and the early diuretic phases. Renal plasma flow in the group of patients at one month after the oliguric onset was about 45% of the normal, however, it returned to normal level at six months after the onset. 5. Clinical syndrome of relative hypervolemia was observed in some patients during the oliguric phase or hypertensive diuretic phase. Characteristic hemodynamic findings were high cardiac output and normal to relatively increased peripheral resistance in these cases. Relatively increased circulating blood volume due to decreased effective vascular space was suggested for the mechanism of relative hypervolemia. 6. Cardiac hemodynamic alteration returned to normal during late stage of the diuretic phase, while renal hemodynamic changes were normalized at six months after the onset.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.135-145
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• 1988

Dopamine when given icv induces antidiuresis along with transient natriuretic tendency, and it has been suggested that both subtypes of central dopamine receptors may influence renal function differentially. This study was undertaken to delineate the role of central $D_2$ receptors employing domperidone (DOM), a selective $D_2$ antagonist. DOM icv elicited antidiuresis and antinatriuresis in doses ranging from 15 to $135{\mu}g/kg$. GFR and RPF as well as sodium excretion decreased. Systemic blood pressure increased slightly. Intravenous DOM did not elicit significant changes in sodium excretion. Denervation of the kidney abolished the hemodynamic change induced by icv DOM, but sodium excretion decreased on both innervated and denervated kidneys. No diuretic tendency was uncovered by the denervation. Dopamine, $150{\mu}g/kg$ icv, produced antidiuresis along with decreases in hemodynamics. These effects were not affected by DOM-pretreatment, and no natriuretic tendency was unveiled. Bromocriptine, a $D_2$ receptor agonist, $200{\mu}g/kg$ icv, elicited marked diuresis and natriuresis, which were completely abolished by DOM-pretreatment. Apomorphine, another prototype of $D_2$ agonist, $150{\mu}g/kg$ icv, produced diuresis and natrituresis with increases in renal hemdoynamics, followed by decreases in all parameters. DOM-pretreatment did not affect the renal hemodynamic effects, wherease the increases in urine flow and sodium excretion were markedly reduced by DOM, Present study suggests that central $200{\mu}g/kg$ receptors mediate natriuretic and diuretic influence to the kidney, possibly through mediation of natriuretic humoral factor, and provide further evidence supporting the hypothesis that central $200{\mu}g/kg$ receptors mediate antidiuretic influence via nerve pathway, whereas natriuresis are brought about through mediation of central $200{\mu}g/kg$ receptors.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.49-61
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• 1985

In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.119-127
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• 1985

The renal function is under regulatory influence of the central nervous system, mainly through activation of sympathetic nerve to the kidney, and it was recently reported that clonidine, an agonist to ${\alpha}_2$-adrenoceptors, induces diuresis and natriuresis when injected directly into a lateral ventricle of the rabbit brain (i.c.v.). This study was undertaken, therefore, to obtain further information as to the role of the central ${\alpha}_2$-adrenoceptors in regulating renal function, by observing the effects of i.c.v. yohimbine, a specific antagonist of adrenoceptors of ${\alpha}_2$-type, on the rabbit renal function, and to elucidate the mechanism involved in it. With 10 ${\mu}g/kg$ i.c.v. of yohimbine sodium excretion transiently increased along with increasing tendency of urine flow, renal plasma flow and glomerular filtration rate. These responses decreased with increasing doses. With 100 and 300 ${\mu}g/kg$ i.c.v. marked antidiuresis and antinatriuresis as well as profound decreases of renal perfusion and glomerular filtration were noted. Systemic blood pressure transiently increased. In reserpinized rabbits, 100 ${\mu}g/kg$ yohimbine i.c.v. did not produce any significant changes in urine flow, sodium excretion as well as in renal hemodynamics. The pressor response was also abolished. In preparations in which one kidney was denervated and the other left intact as control, i.c.v. yohimbine elicited typical antidiuretic antinatriuretic response in the innervated control kidney, whereas the denervated experimental kidney responded with marked diuresis and increases in excretory rates of sodium and potassium and in osmolar clearance in spite of absence of increased filtration and perfusion . Systemic blood pressure responded as in the normal rabbits. These observations indicate that i.c.v. yohimbine affects renal function in dual ways in opposite directions, the first being the antidiuretic antinatriuretic effects which results from decreased renal perfusion and glomerular filtration due to sympathetic activation and which is predominantly expressed in the normal rabbits, and the second less apparent effect being the diuretic and natriuretic action which is not mediated by nerve pathway but brought about by some humoral mechanism and which is effected by decreased sodium reabsorption in the tubules, possibly of the proximal portion.

• Herbal Formula Science
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• v.21 no.1
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• pp.1-15
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• 2013

Objectives : This article is a study on to which categories of modern diseases blood stasis patterns are assigned and the meaning of blood stasis interpreted with perspectives of Korean Medicine and modern medicine. Methods : We reviewed "Neijing", "Shanghanlun", "Yilingaicuo", "Xuezhenglun" and other books and modern clinical papers related with blood stasis. Results : 1. Blood stasis patterns are related with disorders of hemorrheology, hemodynamics, platelet function, microcirculation, microelements and endothelial damage. 2. From the types of syndrome differentiation, diverse diseases classified in type of qi deficiency with blood stasis and type of blood stasis due to qi stagnation are reported, which reflects qi and blood are closely connected. And many diseases are classified in type of kidney deficiency with blood stasis, which has something in common with chronic diseases can achieve effect from treatment considering blood stasis. 3. Diseases related with kidney involve menopausal disorder, mazoplasia, prostatitis, erectile dysfunction, chronic nephritis, renal calculus, osteoporosis and bursitis. Diseases related with heart involve coronary artery disease, arrhythmia and cerebral thrombosis. Diseases related with spleen involve gastritis, colonitis and digestive organ ulcer. Diseases related with liver involve hepatitis, hyperthyroidism and stroke. Diseases related with lung involve neurodermatitis, bronchitis and paranasal sinusitis. Conclusions : Blood stasis pattern which is one of the areas to draw medicine's attention has broad clinical application.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.221-232
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• 1988

Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled, streptozotocin (STZ)-induced diabetes is attributable to diabetes-associated, enhanced renal vasoconstrictor influence of endogenous thromboxane $(TX)A_2$. Rats which were injected with STZ after pretreatment with 3-O-methyl glucose (3OMG), an agent which prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (RBF; ml $min^{-1}$ $gKw^{-1}$; electromagnetic flow probe), systemic arterial pressure (BP; mm Hg) and renal vascular resistance (RVR;BP $RBF^{-1})$in pentobarbital-anesthetized rats during a control period were $5.9{\pm}0.3$(P<0.1_{VS}. CR), $115{\pm}3$ and $20.3{\pm}1.0$(P<0.1_{VS}. CR) for STZR (n=15), and $8.4{\pm}0.4$, $123{\pm}3$ and $15.1{\pm}0.8$ for age-matched control rats (CR; n= 15), respectively. Basal values of RBF, BP and RVR in 3OMG pretreated STZR were identical to CR. In preparations shown capable of renal vasodilatation, OKY 1581 (1 mg/kg, i.v. followed by 0.4 mg/kg min infusion) abolished arachidonate-induced $(TX)A_2$ synthesis, but did not alter basal BP, RBF or RVR in either STZR or CR (n=4/group). Similarly, i.r.a. infusion of SQ29548 (100 ng/ml RBF) abolished renal vasoconstriction induced by a TX/prostaglandin endoperoxide mimic, U46619, but had no discern able affect on RVR in either STZR (n=8) or CR (n=8). The data indicates that $TXA_2$ does not participate in the elevated basal RVR of STZR which are associated with the diabetic state.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.137-146
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• 1992

The central tryptaminergic system has been shown to play an important role in the regulation of renal function: $5-HT_1$ receptor mediate diuresis and natriuresis, whereas both $5-HT_2$ and $5-HT_3$ mediate antidiuresis and antinatriuresis. Recently, $5-HT_1$ receptors are further subdivided into many subtypes, and central $5-HT_{1A}$ subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of $5-HT_{1B}$ subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective $5-HT_{1B}$ agonist in doses ranging from 8 to $750\;{\mu}g/kg$ icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with $250\;{\mu}g/kg$ icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective $5-HT_1$ blocker. Both ketanserin and MDL 72222, selective $5-HT_2$ and $5-HT_3$ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, $5-HT_{1A}$ blocker, affect the TFMPP effects. These observations suggest that central $5-HT_{1B}$ receptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.