• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.25-31
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• 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 Physiology
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• v.21 no.1
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• pp.13-22
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• 1987

Effects of synthetic atrial natriuretic peptide and furosemide on the cardiovascular and renal functions were examined in the freshwater turtle, Amyda japonica. Both atria and ventricle of turtle contained an immunoreactive atrial natriuretic peptide. Synthetic rat atrial natriuretic peptide (atriopeptin III) and turtle atrial extract caused a decrease in mean arterial blood pressure and the vasodepressor effect was dose-dependent. In hydrated turtles received either atriopeptin III or turtle atrial extract, no significant change in renal function was observed until 100 min except a slight natriuresis at 60 or 100 min after injection of 30 ug/kg atriopeptin III or atrial extract, respectively. However, furosemide, 2 mg/kg, caused marked diuresis, natriuresis and kaliuresis. In non-hydrated turtles, no significant change in renal function was observed until 6 hrs following injection of 30 ug/kg atriopeptin III. Plasma aldosterone decreased at 2 hr and increased at 24 hr after injection of atriopeptin III although plasma renin concentration did not change. But, furosemide caused persistent diuresis, natriuresis and kaliuresis. Additionally, plasma aldosterone and renin concentrations were significantly increased at 24 hrs after injection of furosemide. In conclusion, we suggest that the freshwater turtle may have an atrial natriuretic peptide in heart and vascular receptors for atrial natriuretic peptide, and that atrial natriuretic peptide is more important in the regulation of blood pressure rather than that of renal function in freshwater turtles. We also suggest that an increased plasma renin concentration caused by furosemide may not be due to the sodium concentration delivered to macula densa, but due to the dehydration caused by persistent diuresis and natriuresis.

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

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

• Mycobiology
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• v.48 no.5
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• pp.399-409
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• 2020

Many of the 𝛽-glucans are known to have antihypertensive activities, but, except for angiotensin-converting enzyme II inhibition, the underlying mechanisms remain unclear. Corin is an atrial natriuretic peptide (ANP)-converting enzyme. Activated corin cleaves pro-ANP to ANP, which regulates water-sodium balance and lowers blood pressure. Here, we reported a novel antihypertensive mechanism of 𝛽-glucans, involved with corin and ANP in mice. We showed that multiple oral administrations of 𝛽-glucan induced the expression of corin and ANP, and also increased natriuresis in mice. Microarray analysis showed that corin gene expression was only upregulated in mice liver by multiple, not single, oral administrations of the 𝛽-glucan fraction of Phellinus baumii (BGF). Corin was induced in liver and kidney tissues by the 𝛽-glucans from zymosan and barley, as well as by BGF. In addition to P. baumii, 𝛽-glucans from two other mushrooms, Phellinus linteus and Ganoderma lucidum, also induced corin mRNA expression in mouse liver. ELISA immunoassays showed that ANP production was increased in liver tissue by all the 𝛽-glucans tested, but not in the heart and kidney. Urinary sodium excretion was significantly increased by treatment with 𝛽-glucans in the order of BGF, zymosan, and barley, both in 1% normal and 10% high-sodium diets. In conclusion, we found that the oral administration of 𝛽-glucans could induce corin expression, ANP production, and sodium excretion in mice. Our findings will be helpful for investigations of 𝛽-glucans in corin and ANP-related fields, including blood pressure, salt-water balance, and circulation.

• 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.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.

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

• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.59-71
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• 1984

To explore the regulatory roles of CNS on the renal function, clonidine, a specific presynaptic ${\alpha}-adrenoceptor$ agonist, was administered into a lateral ventricle of the brain (icv) and the changes of renal function were studies in urethane-anesthetized rabbits. $5{\mu}g/kg$ icv elicited no significant changes in renal function. However, $15{\mu}g/kg$ induced marked natriuresis and kaliuresis for 20 min. Neither RPF nor GFR changed significantly. The fractional sodium reabsorption was significantly reduced, indicating that the renal action was of the tubular origin. Changes of systemic blood pressure were not contributory to the renal action. Yohimbine, a specific antagonist for presynaptic ${\alpha}-adrenoceptor$, when given icv in doses of $100{\mu}g/kg$ 20 min prior to clonidine, completely abolished the renal action of icv clonidine. Yohimbine icv did not produce any significant changes in renal function. Intravenous clonidine, $15{\mu}g/kg$, elicited antidiuresis and decrement of renal function immediately after administration, followed by a slight tendency toward natriuresis, but no natriuresis corresponding to those seen after the icv clonidine were observed, indicating that in the renal action of icv clonidine no direct action is involved. These observations indicate that the central sympathetic tone plays a role in the regulation of renal function in the rabbit.

• YAKHAK HOEJI
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• v.19 no.4
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• pp.227-233
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• 1975

The diuretic action of guanethidine was investigated in the dogs by means of the stop-flow technique. Guanethidine increased the rejection of sodium in the ascending limb of Henle's loop, as well as in the proximal and distal tubules, resulting in the decrease of the concentrating ability of the kidney, in marked natriuresis and diuresis. It was also effective during an osomotic diuresis, which was induced by infusing 10% mannitol can exhibit its effect even under the diuretic action of mercurophylline, suggesting a different mechanism from that of mercuric iuretics.