• The Korean Journal of Pharmacology
• /
• v.21 no.1
• /
• pp.49-61
• /
• 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
• /
• v.18 no.1
• /
• pp.1-10
• /
• 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.

• YAKHAK HOEJI
• /
• v.35 no.2
• /
• pp.85-98
• /
• 1991

Verapamil, $Ca^{2+}$-channel blocker, when given into vein or into carotid artery, produced the decrease of urine flow accompanied with the decreased amounts of Na$^{+}$ and $K^{+}$ excreted in urine ($E_{Na}, E_{K}$) and with the decreased clearances of free water (C$_{H_2O}$) and osmolar substance (C$_{osm}$), and then increased reabsorption of Na$^{+}$ and $K^{+}$ in renal tubules (R$_{Na}$, R$_{N}$), glomeruler filtration rate (GFR) and renal plasma flow (RPF) were inhibited when verapamil was given into carotid artery, but were only tendency of reduction when given intravenously. Verapamil, when infused into a renal artery, exhibited diuresis accompanied with the increased GER, RPF, E$_{Na}$ and E$_{K}$, with the decreased filtration fraction (FF) in only infused kidney. At the same time, $C_{H_2O}$ was not changed, R$_{Na}$ and R$_{K}$ were reduced. Antidiuretic action by verapamil administered into vein or into carotid artery in normal kidney was reversed to diuretic action in denervated kidney. At this time, parameters of renal function exhibited the opposite phenomena compared to that elicited by verapamil in normal kidney, wherease renal denervation did not influence the action of verapamil infused into a renal artery. Above results suggest that verapamil produce both antidiuresis through nervous system centrally, not endogenous substances and diuresis by direct action in the kidney. Diurectic action are caused by hemodynamic improvement through dilatioon of vas efferense and by greatly inhibited reabsorption of electrolytes in distal tubules.

• The Korean Journal of Pharmacology
• /
• v.14 no.1_2
• /
• pp.25-31
• /
• 1978

It has recently been reported that prostaglandin $(PG)F_{2\alpha}$ produces diruesis and natriuresis when given directly into a lateral ventricle of the brain in rabbits (Kook et al). In this study attempts were made to elucidate the mechanism of the natriuresis utilizing dogs. In mongrel dogs of both sexes weighing 9-l2kg, a lateral ventricle of the cerebrum was cannulated and the agent was delivered in less than 0.2ml of 0.9% saline. $PGF_{2\alpha}$, $100\;{\mu}g$, ivt, elicited mild diuresis, while glomerular filtration rate and systemic blood pressure remained unchanged. In 8 chloralso-anesthetized, hydrated dogs undergoing water diuresis, ivt $PGF_{2\alpha}$ produced antidiuresis concomitant with marked natriuresis, which resembles the action of large doses of Arginine vasopressin in doses of 0.3-1.5mu/kg/min produced marked natriuresis. In 9 experiments, $PGF_{2\alpha}$ was given intraventricularly during the maximal diuresis induced by ADH. The kidney responded with significant natriuresis though less marked and transient than during water diuresis. It is thus concluded that beside ADH still other natriuretic factor(s) may be involved in the natriuresis induced by ivt $PGF_{2\alpha}$ in the dog.

• The Korean Journal of Pharmacology
• /
• v.16 no.1 s.26
• /
• pp.15-24
• /
• 1980

As it has been reported that opioids such as morphine and methionine-enkephalin induced antidiuresis and antinatriuresis along with decrease in renal hemodynamics when given intracerebroventricularly(ivt), the renal action of ivt naloxone, a pure antagonist of morphine, and its influence upon the morphine action were investigated in this study. Less than $0.3{\mu}M/kg$ naloxone ivt did not change renal funtion. $1{\mu}M/kg$ ivt tended to, increase urine flow rate and induce transient natriuresis. $3{\mu}M/kg$ ivt produced transient: natriuresis. $3{\mu}M/kg$ ivt produced marked diuresis and natriuresis without any changes of renal hemodynamics. $10{\mu}M/kg$ ivt produced significant increases of urine flow rate and excretion of sodium without any changes of renal hemodynamics. Morphine $0.03{\mu}M/kg$ ivt produced marked decrement in renal hemodynamics along with decreases of water and sodium excretion, as previously shown by Kang. These effects of ivt morphine were completely abolished by the pretreatment with $0.3{\mu}M/kg$ naloxone. These observations provide further evidence that opiate receptors and endorphins in the brain might play an important role in the center-mediated regulation of the renal function in the rabbit.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.2
• /
• pp.195-200
• /
• 1997

Water transport in highly-permeable membranes is facilitated by some specialized pathways, which are called aquaporins (AQP). AQP1 (AQP-CHIP) is the first recognized aquaporin identified from red cells and renal proximal tubules. Up until now 4 other aquaporin homologs have been reported. Each aquaporin has its unique tissue distribution and regulatory mechanims. To elucidate molecular mechanisms for their transcription regulation and tissue-specific expression isolation of aquaporin genes is required. To clone promoters of the AQP family mouse genomic library was screened by the 1st exon-specific probe of AQP4, and 5 different plaques were positively hybridized. Phage DNAs were purified and characterized by restriction mapping and sequencing. One of them is the mouse AQP-CD gene. The gene was consisted of 4 exons and the exon-intron boundaries of mouse AQP-CD gene were identified at identical positions in other related genes. The 5'-flanking region of AQP-CD gene contains one classic TATA box, a GATA consensus sequence, an E-box and a cyclic AMP-responsive element. The cloning of the mouse AQP-CD gene, of which product is expressed in the collecting duct and is responsible for antidiuresis by vasopressin, will contribute to understand the molecular mechanisms of tissue-specific expression and regulation of AQP-CD gene under various conditions.

• The Korean Journal of Physiology
• /
• v.21 no.2
• /
• pp.291-296
• /
• 1987

There have been reports on the aberration of the control mechanisms of the blood pressure, hormone secretion, and renal functions in spontaneously hypertensive rats (SHR). However, the contribution of the renin-angiotensin system in the maintenance of high blood pressure in SHR is still controversial. Recently, it has been reported that the negative feedback short loop control mechanism of the renin-angiotensin system may be changed in SHR. In the present experiment, it was attempted to explore the possible alterations in the effect of arginine vasopressin (AVP) on the renal function in SHR. Experiments have been done in anesthetized SHR as well as in normotensive Wistar and Sprague-Dawley rats as control groups. Pharmacologic doses of AVP (10-13 mU/rat/10 min) decreased urine volume, excreted amount of creatinine and para-amino-hippuric acid. No differences in these parameters was observed between normotensive and hypertensive rats. AVP increased sodium and potassium excretion, but the responses in SHR were suppressed as compared with normotensive rats. Intravenous infusion of AVP also increased blood pressure in normotensive and hypertensive rats and a vasopressor effect of AVP was attenuated in SHR. There was a positive correlation between the changes in blood pressure and excreted amount of sodium during AVP infusion. These data suggest that the attenuated natriuretic effect of intravenous infusion of AVP may be due to a difference in renal tubular responsiveness to AVP but not due to a difference in vasopressor responsiveness.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.5
• /
• pp.555-563
• /
• 1998

The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 ${\mu}g/kg,$ elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 ${\mu}g/kg$ diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 ${\mu}g/kg$ icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 ${\mu}g/kg$ given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 ${\mu}g/kg$ muscimol was given 3 min prior to 30 ${\mu}g/kg$ of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.

• Journal of Acupuncture Research
• /
• v.19 no.1
• /
• pp.175-188
• /
• 2002

Objective : The effects of SP6(Sanyinjiao, 三陰交) acupuncture stimulation on bladder parasympathetic nerve activity (PNA), tibial nerve activity (TNA) as well as blood pressure were examined in anesthetized rats and the results are as follows. Methods : The parasympathetic nerve leading to the bladder was exposed retroperitoneally, and the tibial nerve in the hindlimb was exposed through inguinal area. PNA and TNA were recorded using a bipolar platinum-iridium wire electrode and it was connected to preamplifier. Blood pressure was measured using cannula that was inserted into femoral artery and was recorded with blood pressure sensor that is connected with transducer amplifier. The mean value of all parameters measured for 30 seconds before the stimulation was expressed as 100%. An acupuncture needle was inserted into the SP6 region to a depth of 4 mm. Results : Under intact state (IS), acupuncture stimulation for 120 seconds induced significant increase of PNA which was accompanied with decrease of blood pressure. At the same time, TNA showed temporary increase only with acupuncture stimulation. In 4 mg/kg of naloxone-administrated state (NAS), significant decrease of PNA was seen and it was accompanied with increase of blood pressure. TNA also showed temporary increase only with acupuncture stimulation under the NAS just like the IS. Conclusion : consider that SP6(Sanyinjiao, 三陰交) acupuncture stimulation activated parasympathetic nerve and caused vasodilation to lead into the diuresis, but naloxone reversed the effect of acupuncture for antidiuresis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.3
• /
• pp.315-323
• /
• 1997

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 intracerebrovent-ricularly(icv)-administered PAPP(p-aminorhenylethyl-m-trifluoromethytphenyl piperazine, LY165163), a selective agonist of $5-HT_{1A}$ receptors. PAPP in doses ranging from 40 to $350{\mu}g/kg$ 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 $350{\mu}g/kg$ 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, $40{\mu}g/kg$ 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.