• 대한약리학회지
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• 제14권1_2호
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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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• 제21권1호
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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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• 제2권5호
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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.

• 대한약리학회지
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• 제16권1호
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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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• 제48권5호
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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.

• 대한약리학회지
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• 제26권2호
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• pp.153-160
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• 1990

5-Hydroxytryptamine(5-HT)를 가토뇌실내로 투여 (icv)하면 이뇨와 Na배설증가가 초래되며, 이러한 작용은 $5-HT_1$ 수용체길항제인 methysergide에 의하여 차단되므로 중추성 신장기능조절에 있어 중추 tryptamine계의 관련이 시사된 바 있다. 본 연구에서는 $5-HT_2$ 길항제로 알려진 ketanserin (KET)를 이용하여 $5-HT_2$ 수용체의 역할을 구명하고자 하였다. KET $120\;{\mu}g(=0.3{\mu}moles)/kg$ icv는 신혈류역학에는 아무런 변동을 일으키지않으나 유의한 Na배설증가를 초래하여, 세뇨관에서의 Na 재흡수 감소가 시사되었다. 전신혈압은 약간 감소하였다. 정맥내 투여시에는 유의한 기능변동을 볼 수 없었다. 5-HT $200{\mu}g/kg$ icv는 경미하나 유의한 Na배설증가 및 이뇨작용을 나타냈다. 그러나 신장기능에 그다지 큰 영향을 미치지 않는 양인 $40{\mu}g/kg$의 KET icv후에는 5-HT의 작용이 크게 강화되어, Na배설분획이 9.3%에 달하였다. Norepinephrine, dopamine, histamine과 같은 다른 생체아민의 신장작용은 KET전처치에 의하여 영향받지 아니하였다. 본 연구는 중추 $5-HT_1$ 수용체와는 반대로 중추 $5-HT_2$ 수용체는 항이뇨 및 Na배설감소를 매개하고 있으며, 중추 tryptamine계는 신장기능을 이중적으로 조절하고 있음을 시사하였다.

• 대한약리학회지
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• 제28권2호
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• pp.137-146
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• 1992

신장기능조절에 있어서 중추 tryptamine계가 관련되어 있으며, $5-HT_1$수용체는 이뇨적인 역할을 하고 있는 반면에 $5-HT_2$ 및 $5-HT_3$수용체는 항이뇨적인 영향을 미치고 있음이 밝혀진 바 있다. 또한 $5-HT_1$수용체도 단일하지 않고 여러 subtype가 존재함이 알려져 있다. $5-HT_{1A}$수용체의 역할에 관해서는 신기능에 이뇨적인 영향을 미치고 있음이 시사된 바 있다. 본 연구에서는 중추 tryptamine성 신기능 조절에 있어서 $5-HT_{1B}$수용체의 역할을 구명하고자 하였다. 선택적 $5-HT_{1B}$ agonist인 TFMPP $8{\sim}750\;{\mu}g/kg$을 가토 측뇌실내로 투여하면 투여량에 비례하여 이뇨 및 Na과 K 배설의 증가를 초래하였으며, $250\;{\mu}g/kg$ 투여시에는 Na의 배설 분획이 5.44%까지 증가하였다. Na배설 촉진작용은 신혈류역학의 증가 보다도 훨씬 지속하여, 세뇨관에서의 Na재흡수 감소작용이 체액성 기전임을 시사하였다. TFMPP $250\;{\mu}g/kg$ icv투여시에 natriuresis와 함께 혈장내 atrial natriuretic peptide 농도가 약 6배 증가되었다. TFMPP $250\;{\mu}g/kg$을 정맥내로 투여하였을때는 뇌실내 투여시와는 상이하게 신기능에 별다른 유의한 변동을 초래하지 않았다. 이와같은 TFMPP의 diuresis 및 natriuresis는 각각 $5-HT_2$ 및 $5-HT_3$ 수용체의 선택적 antagonist인 ketanserin과 MDL 72222의 전처치에 의하여 차단되지 않았으며, methysergide에 의해서도 억제되지 않았다. 또한 $5-HT_{1A}$ antagonist로 알려진 NAN-190도 TFMPP의 작용을 차단하지 못하였으며 S(-)-propranolol도 영향을 미치지 않았다. 본 연구의 결과 중추 $5-HT_{1B}$수용체는 신장기능에 이뇨 및 Na배설 촉진적인 영향을 미치고 있고 이작용에 atrial natriuretic peptide가 관여함을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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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.

• 대한약리학회지
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• 제20권2호
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• pp.59-71
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• 1984

신장기능에 대한 중추신경계의 역할을 구명코자. presynaptic ${\alpha}-adrenoceptor$의 선택적 작동약인 clonidine을 urethane마취 가토의 측뇌실내로 (icv)투여하여 신장기능의 변동을 관찰하였다. $5{\mu}g/kg$ icv이하의 양으로는 신장기능의 유의한 변동을 볼 수 없었으나, $15{\mu}g/kg$ icv 으로는 20분간에 걸쳐 현저한 Na 및 K배설 증가를 볼 수 있었다 이 때 신혈류 및 사구체 여과율은 유의한 변동을 나타내지 아니하였다. 또 이때 Na 재흡수율은 유의하게 감소하였으며, Na배설증가 작용이 세뇨관에서의 Na재흡수 억제에 기인함을 알 수 있었다. 전신혈압 변동은 이 작용에 기여하지 아니하였다. Presynaptic ${\alpha}-adrenoceptor$에 대한 선택적 길항약인 yohimbine $100\;{\mu}g/kg$을 clonidine투여 20분전에 측뇌실내로 투여하면 clonidine의 신장작용이 완전히 차단되었다. 이 량의 yohimbine은 측뇌실내 투여시 신장기능에 아무런 변동도 초래하지 아니하였다. $15\;{\mu}g/kg$ clonidine을 정맥내로 투여하면 투여 직후에 뇨량 감소와 신장기능 감퇴를 초래한 뒤 후기에 약간의 Na배설증가의 경향을 보였으나, clonidine을 icv로 투여하였을 때 볼 수 있던 만큼의 Na배설증가는 볼 수 없었다. 따라서 icv clonicine의 신장작용에는 신장에 대한 clonidine의 직접작용이 관여하지 않음을 알 수 있었다. 이 연구결과는 가토의 신장기능 조절에 있어서 중추의 교감신경 긴장도가 중요한 역할을 하고 있음을 시사하였다.

• 약학회지
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• 제19권4호
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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.