안지오텐신 II 유발 고혈압에서 Endothelin, 이뇨호르몬, 산화질소계의 발현 변화
Altered Regulation of Endothelin, Atrial Natriuretic Peptide, and Nitric Oxide Systems in Angiotensin II-induced Hypertension
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연구배경: Endothelin은 대표적인 혈관수축물질이며, 산화질소와 심방 나트륨 이뇨 펩티드(atrial natriuretic peptide)는 대표적인 혈관이완물질이다. 안지오텐신 II 유발고혈압 모델에서 신장과 대동맥에서 이런 물질들이 국소적으로 어떻게 조절되는지 규명하고자 하였다. 방법: Sprague-Dawley 흰쥐를 사용하였으며, 안지오테신 II (100 ng•min-1•kg-1)를 오스모틱 미니펌프를 사용하여 14일간 지속적으로 주입하였다. 실험 당일 혈압을 측정하였으며, 산화질소 합성효소의 발현 정도는 반정량적이뮤노블롯법(immunoblotting)으로 평가하였다. Endothelin 계와 이뇨호르몬계는 real-time polymerase chain reaction 을 이용하여 발현 정도를 평가하였다. 결과: 실험군에서 고혈압이 유발되었으며, 신장의 사구체여과율이 감소하였다. Endothelin-1의 발현은 대동맥과신장에서 모두 증가하였고, 그 수용체는 두 군 간에 발현변화의 차이를 보이지 않았다. 혈관내피세포 산화질소 합성효소(endothelial nitroc oxide synthase)의 단백 발현이대동맥에서 감소하였다. 반면 이뇨호르몬과 그 수용체는두 군 간의 발현 변화의 차이를 보이지 않았다. 결론: 안지오텐신 II 유발 고혈압 모델의 대동맥과 신장에서 endothelin 1의 mRNA 발현증가와 대동맥에서 산화질소 합성효소의 발현감소가 고혈압의 유발에 관여하였을 것으로 생각된다.
Abstract
Background: The present study aimed to determine the changes of endothelin (ET), nitric oxide, and atrial natriuretic peptide (ANP) systems in the kidney and aorta in angiotensin (Ang) II-induced hypertension. Methods: Male Sprague-Dawley rats were used. Ang II (100 ng•min-1•kg-1) was infused through entire time course. Fourteen days after beginning the regimen, aorta and kidney were taken. The protein expression of nitroc oxide synthase (NOS) was determined by semiquantitative immunoblotting. The mRNA expression of components of ET, NOS, ANP system was determined by real-time polymerase chain reaction. Results: Hypertension was developed in the experimental group. mRNA expression of ET-1 in the aorta and kidney was increased. The protein expression of endothelial NOS (eNOS) was decreased in the aorta,while that of inducible NOS and neuronal NOS remained unaltered. mRNA expression of ANP, natriuretic peptide type (NPR)-A, and NPR-C was not changed in the aorta. Conclusions: Based on these results, it seems that in Ang II-induced hypertensive rats, increased expression of ET-1 in the aorta and kidney, and decreased eNOS expression in the aorta contribute to the pathogenesis of hypertension.
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