Normotensive 및 spontaneously hypertensive rat에서 대동맥 평활근의 atriopeptin에 대한 감수성의 비교 연구

의학과/박사[영문] [한글] Atriopeptin 또는 atrial natriuretic factor(ANF)는 심 방근에서 합성되어 secretory granules게 저장되어 있다가 심방이 팽창되거나 sodium load등의 자극으로 분비되어 혈장 을 관류하여 여러 target organ으로 가서 Na**+ 배설 및 요량 증가, aldosterone, antidi uretic hormone의 분비 억제 등, 여러가지 작용을 나타낸다(de Bold, 1981). 사람에서 나타나는 본태성 고혈압을 연구자기 위해 많이 이용되는 spontaneously hyper tensive rat(SHR)에서 적출한 대동맥 평활근이 ANF에 대한 감수성이 normotensive rat(NT R)과 다를지 모른다는 가설하에 Van de Voorde 및 Leusen(1986)의 방법으로 하행 대동맥 을 적출하여 ANF에 대한 감수성을 비교하고자 본 실험을 시행하여 다음과 같은 결과를 얻 었다. 1. Norepinephrine(NE)에 대한 NTR과 SHR의 대동맥 평활근의 감수성 및 수축력에 차이 가 없었다. 이때 양군의 대동맥 평활근의 수축력은 ANF를 첨가하였을 때 첨가하지 않은 대조군보다 감소되었으며 그 정도는 첨가된 ANF외 농도에 비례하였다. 2. NE으로 유도된 대동맥 평활근의 수축력을 감소시키는 ANF의 효과가 NTR보다 SHR에서 더 크게 나타나는 경향이지만 2.5mM Ca**2+에서는 100ng/m1 ANF를 첨가하고 5×10**-8 및10**-7M의 NE으로 유도된 수축반응에서만 양군간에 통계적으로 유의한 차이를 보였고, 50ng/ml 이하의 ANF농도에서는 의의가 없었다. 그러나 KH 용액내 Ca**2+ 농도를 1.8mM로 감소시켰을때 50ng/ml 및 100ng/ml ANF의 이 완 효과가 SHR에서 NTR보다 더 크게 나타나 통계적으로 유의하였다. 3. NTR 및 SHR에서 적출한 대동맥 평활근을 K**+으로 경축시켰을때 낮은 K**+ 농도에서 첨가한 ANF에 의하여 그 수축력이 감소되었으나 NTR 및 SHR 양군간의 차이는 없었다. 4. 2.5mM Ca**2+에서 고농도 K**+과 NE에 의한 수축력과 이에 대한 ANF의 이완 효과가 NTR 및 SHR에서 차이가 없었지만 1.8mM Ca**2+에서는 SHR에서 유의하게 더 컸다. 이상의 실험 결과, spontaneously hypertensive rat에서 적출한 대동맥 평활근의 ANF에 대한 감수성이 normotensive rat 보다 더 크다는 것을 알 수 있다. The Comparison Study on the Sensitivity of Aortic Vaseular Smooth Muscle isolated from Normotensive and Spontaneously Hypertensive Rat to Atriopeptin Hyeung Kyu Yang Department of Medical Science The Graduate School, Yonse University (Directed by Professor Doo Hee Kang, M.D., Ph.D.) Atriopeptin or atrial natriuretic factor (ANF) is synthesized and stored within the secretory granules of cardiac atrial myocrtes and is secreted from the cardiac myocytes into the blood in response to atrial distension and sodium load and acts on remote receptor organs such as the kidney, adrenal gland, central nervous system, etc. (de Bold, 1981). The spontaneously hypertensive rat(SHR) has been widely used as an animal model for studios on human essential hypertension. The present study was intended to compare the sensitivity of aortic vascular smooth muscle isolated from normotensive rats (NTR) and SHR to ANF by a modified method employed by Van de Voorde and Lensen (1986) under the hypothesis that vascular smooth muscle from SHR would show a greater hypersensitivity to ANF than vascular smooth muscle isolated from NTR. The results were summarized as follows. 1. The vascular sensitivity and contractility to nerepinephrine(NE) were not different between NTR and SHR and the contractions of the aortic vascular smooth muscle induced by NE were inhibited in a dose-dependent manner by ANF in both groups. 2. The contractions induced by 5×10**-8 and 1×10**-7 M NE in the vascular smooth muscle of SHR were significantly inhibited by 100 ng/ml ANF as compared to NTR at 2.5 mM external [Ca**2+]. But there was no difference between the two groups at lower doses of ANF. However, at a 1.8 mM calcium concentration, the inhibitory effect of ANF on the vascular smooth muscle isolated from SHR was significantly greater at both 50 and 100 ng/ml of ANF. 3. K**+-induced contractures of aortic vascular smooth muscle of NTR and SHR were also inhibited by ANF in a dose-dependent manner, showing a more pronounced effect in lower concentrations of extracellular K**+. However, the inhibitory effects of ANF on the K**+-induced contractures were not statistically different between NTR and SHR. 4. Contractures induced by 20 mM K**+ and 10**-8M NE of aortic vascular smooth muscles isolated from NTR and SHR were inhibited by ANF, but no difference between NTR and SHR was found at 2.5 mM calcium. However, the inhibitory effect was significantly greater in the aortic vascular smooth muscle isolated from SHR than NTR at a 1.8 mM Ca**2+ Concentration. F개m the above findings, it may be concluded that the aortic vascular smooth muscle of spontaneously hypertensive rats has a greater sensitivity to ANF than that of normotensive rats.restrictio