• 대한소아신장학회:학술대회논문집
• /
• 대한소아신장학회 2007년도 춘계학술대회 및 제8회 연수강좌
• /
• pp.12-14
• /
• 2007

• 대한약학회:학술대회논문집
• /
• 대한약학회 2000년도 춘계총회 및 학술대회
• /
• pp.219.2-219.2
• /
• 2000

• Clinical and Experimental Pediatrics
• /
• 제59권1호
• /
• pp.8-15
• /
• 2016

Purpose: Nephrogenesis is normally accompanied by a tightly regulated and efficient vascularization. We investigated the effect of angiotensin II inhibition on angiogenesis in the developing rat kidney. Methods: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle (control) for 7 days after birth. Renal histological changes were checked using Hematoxylin & Eosin staining. We also investigated the intrarenal expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor 1 (VEGFR1), VEGFR2, platelet-derived growth factor (PDGF)-B, and PDGF receptor-${\beta}$ with Western blotting and immunohistochemical staining at postnatal day 8. Expression of the endothelial cell marker CD31 was examined to determine glomerular and peritubular capillary density. Results: Enalapril-treated rat kidneys showed disrupted tubules and vessels when compared with the control rat kidneys. In the enalapril-treated group, intrarenal VEGF-A protein expression was significantly higher, whereas VEGFR1 protein expression was lower than that in the control group (P<0.05). The expression of VEGFR2, PDGF-B, and PDGF receptor-${\beta}$ was not different between the 2 groups. The increased capillary CD31 expression on the western blots of enalapril-treated rat kidneys indicated that the total endothelial cell protein level was increased, while the cortical capillary density, assessed using CD31 immunohistochemical staining, was decreased. Conclusion: Impaired VEGF-VEGFR signaling and altered capillary repair may play a role in the deterioration of the kidney vasculature after blocking of angiotensin II during renal development.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권24호
• /
• pp.10691-10695
• /
• 2015

Background: Association of angiotensin converting enzyme (ACE) gene polymorphisms with lung cancer susceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally, and ethnically isolated population. The area reports an especially high rate of tobacco usage in a variety of ways of consumption, compared with the rest of the Indian population. Materials and Methods: We conducted a population based case control study in two major high risk region for lung cancer from Northeast India. A total of 151 consecutive lung cancer cases diagnosed histopathologically and equal numbers of controls were recruited with record of relevant sociodemographic information. Blood samples were collected and processed to identify ACE gene polymorphism. Results: Significantly higher (40.4 % vs 29.1%, OR=1.97, CI=1.04-3.72; p=0.037) prevalence of the ACE II genotype was observed among lung cancer cases. Smoking was significantly associated with increased risk of lung cancer (OR=1.70, CI=1.02-2.81; p=0.041). An enhanced risk was also observed for interaction of ACE II genotype with tobacco smoking (OR=4.09, CI=1.51-11.05; p=0.005) and chewing (OR=3.68, CI=1.22-11.13; p=0.021). Conclusions: The present study indicates significant association s of the ACE II genotype with lung cancer in high risk Northeast India.

• The Korean Journal of Physiology and Pharmacology
• /
• 제1권4호
• /
• pp.393-402
• /
• 1997

In the present study, we characterized the angiotensin II (AII)-induced relaxations in the phenylephrine-precontracted rabbit mesenteric arteries with endothelium. 1) AII-induced relaxation was consistently observed in the rabbit mesenteric arteries with and without endothelium, but not in the aortic segment with endothelium. 2) AII-induced endothelium-dependent relaxation was markedly inhibited by $N^w-nitro-L-arginine$ (L-NNA, $100\;{\mu}M$), methylene blue ($10\;{\mu}M$) and LY83583 ($10\;{\mu}M$), respectively. 3) Inhibition of cyclooxygenase with indomethacin ($10\;{\mu}M$) strongly decreased the vasorelaxant response to AII irrespective of the presence of endothelium. 4) 7-Ethoxyresorufin ($1\;{\mu}M$) and clotrimazole ($1\;{\mu}M$), inhibitors of cytochrome P-450-dependent arachidonic acid metabolism, greatly attenuated the vasodilator response to AII. 5) Carbacyclin, arachidonic acid and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) caused concentration-dependent relaxations in the mesenteric artery with endothelium, which were inhibited by L-NNA and methylene blue. 6) AII and $PGF_{2{\alpha}}$ significantly stimulated cyclic GMP formation in the mesenteric arteries with endothelium, which was inhibited by L-NNA and methylene blue, respectively. 7) AII enhanced synthesis of $PGF_{2{\alpha}}$ and 6-keto $PGF_{1{\alpha}}$ from the arterial segments with endothelium, which was inhibitable by indomethacin, but not by L-NNA. In conclusion, the vasorelaxant responses to AII of the rabbit mesenteric artery with endothelium are subserved by arachidonic acid and its metabolites produced via activation of cyclooxygenase and cytochrome P-450 enzyme as well as by nitric oxide.

• Journal of Genetic Medicine
• /
• 제1권1호
• /
• pp.17-22
• /
• 1997

The angiotensin converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular diseases. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction. The insertion/deletion (I/D) polymorphism of the ACE detected by PCR analysis appears to be associated with hypertension in Koreans and its nucleotide was subcloned into T-vector and its nucleotide sequences were determined. We also examined an association between hypertension and genetic variance of ACE. We identified the angiotensin I-converting enzyme genotype in 127 hypertensive and 189 normotensive Korean subjects. The distribution of ACE genotype II, ID, DD were 39.2%, 40.2%, 20.6% respectively and the frequency for ACE alleles I and D were 0.593 and 0.407, respectively in all subjects. The frequency of D allele in Korean males is higher than that of Korean females (male; 0.438 : female; 0.267), and the frequency of I allele in Korean females is higher than that of Korean males (female; 0.733 : male; 0.562). Genotype distributions of angiotensin I-converting enzyme genes in Korean normal adult population were different from that of Caucasians (P<0.001). There were no significant differences in genotype frequency between the hypertensive control group (n=127) and the normotensive group (n=189). We observed significant differences of ACE genotype distribution between the male group and the female group in total (P=0.001) and in hypertensive Korean subjects (P=0.013).

• 미생물학회지
• /
• 제40권4호
• /
• pp.355-358
• /
• 2004

한국의 전통 대두 발효식품 청국장이 정장, 혈액순환 개선 둥의 기능성식품으로 부각되고 있다. 청국장은 발효가 되면서 미생물, 효소, 다양한 생리활성물질이 크게 증가하며, 그 중에는 peptide류도 포함된다. 청국장 Peptide류의 형성은 SDS-PAGE 분석을 통해 확인할 수 있었다. 청국장의 수용성 아미노산중, Tyr, Gln-Lys, Trp, Gln, Lys-Pro 등이 주요성분으로 발견되었고, Lys-Pro (0.083 mg/100 g 시료)가 HPLC에 의해 분리되었다. Lys-Pro은 angiotensin I-converting enzyme (ACE)저해효과 $(IC_{50}=32.1{\mu}m)$를 지니고 있었다. 고혈압군이 분말청국장 20 g을 복용하고 2시간 지났을 때, 수축기 혈압은 15 mmHg, 이완기 혈압은 8 mmHg떨어지는 강하효과가 있었다. 청국장은 ACE 저해제와 혈압강하효과를 갖고 있기 때문에 혈액순환개선에 상당한 도움을 주는 기능성 식품으로 개발될 수 있을 것이다.

• The Korean Journal of Physiology
• /
• 제24권1호
• /
• pp.161-170
• /
• 1990

The effects of $H^{+}$ on the arterial contraction and their mechanisms were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the HEPES-buffered or $CO_{2}/HCO_{3}^{-}$-buffered Tyrode's solution. The contractions induced by agonists (norepinephrine, histamine, serotonin and angiotensin II) or high $K^{+}$ were observed with change of extracellular or intracellular $H^{+}$ concentration. The contractions induced by norepinephrine, histamine, serotonin, angiotensin II or high $K^{+}$ in HEPES-buffered Tyrode's solution were inhibited by increase in extracellular $H^{+}$ concentration and potentiated by decrease in extracellular $H^{+}$ concentration. The degrees of these effects were most evident in the contraction induced by serotonin and angiotensin II, moderate in those by histamine and high $K^{+}$, and least in those by norepinephrine. Maximal contraction by norepinephrine, histamine and high $K^{+}$ were not influenced by change in extracellular $H^{+}$ concentration, but influenced in those contration by serotonin and angiotensin II. The attenuated contractions by an acidic pH were not returned to the level of contraction at normal pH (7.4) by elevation of extracellular $Ca{2+}$ concentration. The agonists (norepinephrine, histamine and serotonin)-induced contractions in $Ca{2+}$-free Tyrode's solution were also attenuated by increase in extracellular $H^{+}$ concentration and potentiated by decrease in extracellular $H^{+}$ concentration. Elevation of $Pco_{2}$ in the $CO_{2}/HCO_{3}^{-}$-buffered Tyrode's solution, which increase the intracellular $H^{+}$ concentration, at constant extracellular pH (7.4), increased the contraction by 30 mM $K^{+}$. From the above results, it is suggested that the decrease in contractions by increase in extracellular $H^{+}$ concentration may be resulted from that $H^{+}$ make the receptors less sensitive to agonists and cell membrane hyperpolarize and then inhibit the $Ca{2+}$ influx as well as $Ca{2+}$ release from intracellular $Ca{2+}$ storage site.

• 약학회지
• /
• 제58권2호
• /
• pp.141-149
• /
• 2014

Background: Oriental lifestyle for treating diseases has been developed and well-accepted for a long time among Koreans. Sasang Constitution theory, originated from Korean traditional medicine, suggests that medication treatment should be differentiated by each patient's body classification (So-yang [SY], So-eum [SE], Tae-yang [TY], and Tae-eum [TE]), in contrary to western medicine's theory that medication should be applied equally by disease indication without such classification. However, the pharmacotherapeutic outcomes of these theories have not been compared to date. In this study, we aimed to compare the two theories by evaluating blood pressure (BP), which is lowered as a therapeutic outcome, among hypertensive patients taking angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs), two most commonly used antihypertensive classes in Korea. Methods: From April 2006 to June 2012, we retrospectively collected data on hypertensive patients with Sasang Constitution classification at Kyunghee University Hospital at Gangdong, one of the East-West collaborative medical centers in Korea. We collected information on age, gender, underlying diseases, antihypertensive drugs (ARB, CCB, ARB+CCB), and BP by reviewing the electronic medical records. We excluded patients with missing blood pressure at baseline or follow-up, or those who had a change in their antihypertensive drug class during follow-up. Results: We selected a total of 573 patients (SY: 165, SE: 158, TY: 0, TE: 250). Baseline BPs were on average 139.0/82.0 mmHg for SY, 137.8/78.5 mmHg for SE, and 138.7/79.2 mmHg for TE. In all three groups, CCBs were the most prescribed, followed by combination therapy with ARB+CCB, then ARBs. BP reduction after 1 month of initial medication was significantly different among the drug classes, but not in Sasang constitutional classification (ARB [SY: -12.4/-4.7, SE: -12.3/-2.5, TE: -8.6/-1.8], CCB [SY: -12.3/-5.4, SE: -13.0/-2.3, TE: -10.8/-6.0], ARB+CCB [SY: -15.6/-6.7, SE: -18.4/-8.1, TE: -20.2/-6.7], drug [$P{\leq}0.05$/P>0.05], constitutional type [P>0.05/P>0.05]). Conclusion: We observed significant differences in reduction of blood pressure by classes of drugs (ARB+CCB>CCB>ARB) but not by Sasang constitutional classification. Therefore, current approach of antihypertensive pharmacotherapy assisted by Western medicine is appropriate for treatment of hypertension. However, further larger scale or prospective studies are required in order to confirm these results.

• The Korean Journal of Physiology and Pharmacology
• /
• 제5권6호
• /
• pp.503-510
• /
• 2001

Long-term treatment of cultured bovine adrenal medullary chromaffin (BAMC) cells with arachidonic acid $(100\;{\mu}M),$ angiotesnin II (100 nM), prostaglandin $E_2\;(PGE_2;\;10\;{\mu}M),$ veratridine $(2\;{\mu}M)$ or KCl (55 mM) for 24 hrs increased both norepinephrine and epinephrine levels in the supernatant. Pretreatment with staurosporine (10 nM), a protein kinase C (PKC) inhibitor, completely blocked increases of norepinephrine and epinephrine secretion induced by arachidonic acid, angiotensin II, $PGE_2,$ veratridine or KCl. In addition, K252a, another PKC inhibitor whose structure is similar to that of staurosporine, effectively attenuated both norepinephrine and epinephrine secretion induced by arachidonic acid. However, K252a did not affect the catecholamine secretion induced by angiotensin II, $PGE_2,$ veratridine or KCl. Our results suggest that staurosporine may inhibit long-term catecholamine secretion induced by various secretagogues in a mechanism other than inhibiting PKC signaling. Furthermore, long-term secretion of catecholamines induced by arachidonic acid may be dependent on PKC pathway.