• Archives of Pharmacal Research
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• 제20권5호
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• pp.389-395
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• 1997

We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated pulmonary arterial tension and pulmonary arterial pressure (PAP) in renal hypertensive rats (RHR) made by complete ligation of left renal artery. Losartan induced a depressor response that was smaller in RHR than in normotensive rats (NR) (3.3 and 7.0 mmHg, respectively, at 3.0 mg/kg, p<0.05), and the response was significantly reduced by $N^{G}$-nitro-Larginine methyl ester (L-NAME). Angiotensin II elevated the PAP (7.6 and 10.8 mmHg at $0.1 {\mu}g/kg$; 20.3 and 23.6 mmHg at $1.0{\mu}g/kg$, respectively) and contracted the isolated pulmonary artery ($pD_2$: 8.79 and 8.71, respectively) from both NR and RHR with similar magnitude, and these effects were significantly enhanced by L-NAME in NR, but not in RHR. Acetylcholine lowered the PAP slightly less effectively in RHR than in NR (3.8 and 6.0 mmHg at 10 .mu.g/kg, respectively) and relaxed the pulmonary artery precontracted with norepinephrine in both rats with similar magnitude ($E_max$: 60.8 and 63.6%, respectively), and the effect being completely abolished after pretreatment.with L-NAME or removal of endothelial cells. These results suggest that nitric oxide interacts with renin angiotensin system to control the pulmonary vascular tension and pulmonary arterial circulation of RHR.R.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.127-130
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• 2002

The present study was aimed to investigate whether the adriamycin-induced nephrosis is associated with an altered regulation of local renin-angiotensin system (RAS) in the kidney. Rats were subjected to a single injection of adriamycin (2 mg/kg body weight, IV) and kept for 6 weeks to allow the development of nephrosis. They were then divided into two groups, and supplied with and without cilazapril, an angiotensin converting enzyme (ACE) inhibitor, in drinking water (100 mg/l) for additional 6 weeks. Another group without adriamycin-treatment served as control. The mRNA expression of renin, ACE, type 1 and type 2 angiotensin II receptors (AT1R, AT2R), and transforming growth factor $(TGF)-{\beta}1$ was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. Adriamycin treatment resulted in heavy proteinuria. Accordingly, the mRNA expression of renin, ACE, and AT1R was increased in the renal cortex, while that of AT2R was decreased. Co-treatment with cilazapril attenuated the degree of proteinuria. While not affecting the altered expression of renin, cilazapril decreased the expression of ACE to the control level. Cilazapril further increased the expression of AT1R, while it restored the decreased expression of AT2R. The expression of $(TGF)-{\beta}1$ was increased by the treatment with adriamycin, which was abolished by cilazapril. An altered expression of local RAS components may be causally related with the development of adriamycin-induced nephrosis, in which AT1R is for and AT2R is against the development of nephrosis.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.45-53
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• 1997

In humans and many animal models with chronic progressive renal diseases, angiotensin-converting enzyme (ACE) inhibitor markedly attenuates the progression of nephropathy. Several studies have reported augmented gene expression and redistribution of renal renin in partial nephrectomized rats. Although precise mechanism(s) is not known, the renin-angiotensin system (RAS) may play an important role in the progression of renal diseases. Thus, this study was undertaken to examine the gene expression of renal renin, angiotensinogen, and $AT_1$ subtypes ($AT_{1A}$ and $AT_{1B}$) in rats with diabetic nephropathy, and the influences of lipopolysaccharide (LPS)-induced septicemia on the gene expression. Four weeks after streptozotocin (STZ) treatment (55 mg/kg, i.p.), rats were randomly divided into LPS-treated (1.6 mg/kg, i.p.) and control rats. At 6 hours after LPS treatment, the rats were killed and the kidney was removed from each rat. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)techniques were used to detect mRNA expression. STZ treatment markedly attenuated body weight gain and significantly increased blood glucose level. Renal renin content (RRC) was significantly decreased in the STZ-treated rats compared to that in control rats. The renal ACE activity between STZ-treated and control rats was not significantly different. Renal renin mRNA level was prominently increased, while angiotensinogen and $AT_{1A}$ mRNA levels were slightly decreased in STZ-treated rats compared to those in controls. $AT_1$B mRNA level did not differ in both groups. Acute LPS treatment did not show any significant changes of mRNA levels of intrarenal RAS components in both groups. These results suggest that intrarenal RAS components were differentially regulated in STZ-treated diabetic rats. Further studies are required to evaluate the relationship between intrarenal RAS and other vasomodulatory systems.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.771-778
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• 1998

To investigate interaction of angiotensin converting enzyme (ACE) inhibitor with local tissue renin- angiotensin system (RAS), changes in gene expression of the RAS components in various tissues in response to chronic administration of an ACE inhibitor, enalapril, were examined in Sprague-Dawley male rats. Enalapril was administered in their drinking water $(3{\sim}4\;mg/day)$ over 8 wk. Plasma and renal ACE activity increased significantly after 4 and 8 wk of enalapril treatment. Renin levels of the plasma and kidney of the enalapril-treated rats markedly increased after 4 wk and decreased thereafter, but still remained significantly higher than those of control rats. Kidney mRNA levels of renin markedly increased after 4 and 8 wk of enalapril treatment, but those of angiotensinogen and ANG II-receptor subtypes, $AT_{1A}$ and $AT_{1B}$, did not change significantly. The liver expressed genes for renin, angiotensinogen and $AT_{1A}$ receptor subtype, but $AT_{1B}$ receptor subtype mRNA was not detectable by RT-PCR. None of mRNA for these RAS components in the liver changed significantly by enalapril treatment. The hypothalamus showed mRNA expressions of renin, angiotensinogen, $AT_{1A}$ and $AT_{1B}$ receptor subtypes. $AT_{1A}$ receptor subtype mRNA was more abundant than $AT_{1B}$ receptor subtype in the hypothalamus as shown in the kidney. However, gene expression of the RAS components remained unchanged during 8-wk treatment of enalapril. In the present study, chronic ACE inhibition increased plasma and renal levels of ACE and renin, but did not affect mRNA levels of other RAS components such as angiotensinogen, ANG II receptor subtypes in the kidney. Gene levels of the RAS components in the liver and hypothalamus were not altered by chronic treatment of enalapril. These results suggest the differential expression of the RAS components in response to enalapril, and localized action and some degree of tissue specificity of enalapril.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.220-225
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• 1993

Effect of BR-900317 on the angiotensin I-induced pressor response in pithed rats and the effects of its single oral administration on plasma angiotensin converting enzyme (ACE) activities in normotensive rats and on the cardiovascular system in hypertensive model rats (SHR, RHR), were compared with those of captopril. BR-900317 attenuated the angiotensin I-induced pressor effects in pithed rats. In a single oral dose administration study, BR-900317 inhibited the plasma ACE activities in a dose-dependent fashion. Duration of the action of BR-900317 was similar to that of captopril. BR-900317 produced antihypertensive effect in spontaneously hypertensive rats and dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive rats without affecting heart rate. These results suggest that the main mechanism of the antihypertensive effect of BR-900317 is the suppression of angiotensin II production due to the inhibition of the ACE.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.155-155
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• 2001

Acute cadmium exposure has been shown to increase sodium reabsorption in kidney through increase in aldosterone secretion in human and rodents. However, the antinatriuresis is not completely explained by hyperaldosteronism. Moreover, it is still controversial that the increase in plasma aldosterone concentration is mediated by the renin-angiotensin-aldosterone system(RAAS).(omitted)

• 대한약리학회지
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• 제28권1호
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• pp.61-74
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• 1992

마취가토에서 혈압유지에 중요한 역할을 하고 있는 교감신경계, renin-angiotensin계, vasopressin계를 차단하였을때의 혈압자체의 변동과 norepinephrine (NE), angiotensin II (AII) 및 vasopressin (VP)의 승압효과의 변동을 조사하였다. 교감신경계와 renin-angiotensin계의 차단에는 각각 교감신경절 차단약인 chlorisondamine (CS)과 pirenzepine (PZ), angiotensin 변환효소억제약인 enalapril (ENAL)를 사용하였다. VP계의 차단에는 혈장 VP농도를 하강시킴이 알려져 있는 kappa opioid 수용체의 작용약인 bremazocine (BREM)을 사용하였다. CS (0.4mg/kg), ENAL (2mg/kg), BREM (0.25mg/kg)은 각각 비슷한 정도의 저혈압상태를 일으켰다. BREM에 의한 저혈압은 VP와 같은 효과를 가진 합성약인 desmopressin으로 유의하게 길항되었으며 BREM에 의한 저혈압이 적어도 일부 혈장 VP농도의 하강과 관계있음을 시사하였다. CS는 ENAL 또는 BREM으로 하강된 혈압을, ENAL은 CS 또는 BREM으로 하강된 혈압을, BREM은 CS 또는 ENAL로 하강된 혈압을, 더욱 하강시켰다. CS, PZ 그리고 ENAL 또는 CS, PZ 그리고 BREM에 의한 저혈압은 CS이외의 세약물에 의한 저혈압보다 심하였다. CS는 NE에 의한 승압효과 뿐만아니라 AII와 VP의 승압효과도 강화시켰다. AII의 승압효과는 또 ENAL과 BREM으로도 증대되었다. VP의 승압효과는 BREM으로도 강화되었다. ${\alpha}$-수용체의 길항약인 phentolamine과 phenoxybenzamine은 AII와 VP승압효과를 강화시켰다. 3승압계 차단이 혈압자체에 미치는 실험결과는 3계가 모두 혈압조절에 관여하고 그 중에서도 교감신경계가 가장 큰 역할을 하고 있음을 가리키고 있다. 한 승압계의 차단하에서, 그 계의 승압 hormone 뿐만아니라 다른 계의 승압 hormone의 승압효과도 증대됨은 이 3승압계가 긴밀한 상호작용을 하고 있는 증거이다.

• 한국동물학회지
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• 제33권1호
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• pp.35-44
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• 1990

생쥐 악하선으로부터 분리한 전 RNA를 poly(U)-sepharose chromatography와 sucrose linear density gradient centrifugation 방법으로 레닌 mRNA를 분리하여 in vitro translation과 immunoprecipitation에 의하여 레닌 mRNA를 확인하였다. 레닌 mRNA로부터 레닌 cDNA를 합성하여 EcoRI inker를 이용하여 pUC19에 삽입시켰고, Taq, polymerase를 이용한 PCR방법으로 합성한 레닌 cDNA는 pUC19의 Hinalll 부의에 삽입하여 재조합 plamid를 각각 작성하였다. 이것을 JM103에 형질전환시켜 레닌 유전자 발현을 유도하여 45,000의 분자량을 갖는 레닌을 얻었으며 이 레닌 단백은 토끼으 혈압을 850115mmHg에서 115-140mmHg로 증가시키는 생리 활성을 나타냈다. 토끼의 신장 DNA를 EMBL3 phage에 삽입시켜 genomic library를 작성한 후, 레닌 cDNA로부터 합성한 probe로 plaque hybridization시켜 genomic 유전자를 갖는 재조합 phage를 분리하였다.

• 대한한의학방제학회지
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• 제24권3호
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• pp.175-193
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• 2016

Objective : Diuretics are effective on the patients with hypertension and heart failure, as well as edema by regulating the function of kidney, which is key organ to maintain the balance of the different electrolytes in the body. The present review article is designed to review the diuretic effect of Korean medicinal prescription base on the experimental studies.Method : For this purpose, every article related to ‘diuresis’ and 'Korean medicinal prescription' were analysed from articles which published at domestic and international journals.Results : 1. Representative Korean medicine prescriptions showed diuretic effect along with electrolyte excretion were Oryeong-san, Paeryung-tang, Hwangryungbokryung-tang and Daeganghwal-tang. 2. Some Korean medicinal prescription including Oryeong-san, Jueryeong-tang, Sipcho-tang distribute diuresis through the inhibition of renin-angiotensin-system. 3. Oryeong-san, Bojungchiseup-tang had a diuretic effect on the down-regulation of aquaporin water channel in the renal collecting duct.Conclusion : Korean medicinal transcriptions have a diuretic effect through several types of mechanism such as along with electrolytes excretion, inhibition of renin-angiotensin system, and down-regulation of water channels.

• Archives of Pharmacal Research
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• 제18권3호
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• pp.169-172
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• 1995

The changes in blood pressure may relate to the alterations of the responsiveness to vasoconstrictors and vasodilators, and these alterations can arise the modifications in the properties of angiotensin II (AII) receptor. In order to examine the changes of AII receptor in the hypertensive mechanism of renin-dependent hypertensive rats (RHRs; two-kidney, one-ligated type), we compared the equilibrium binding characteristics of $[^3H]$All in adrenal cortex and medulla from RHRs and normotensive rats. The dissociation constants of AII binding in both tissues of RHRs were very similar to those in the respective tissue of normotensive rats. However, the maximum binding was increased from 805 to 1050 fmole/mg protein in the adrenal cortex of RHRs, and decreased from 172 to 126 fmole/mg protein in the adrenal medulla of RHRs. These results imply that the up- and down-regulation of the All receptor population on the cell surface of adrenal glands from RHRs are consorted with the elevation of blood pressure and the activation of renin-angiotensin system.