The effect of L-arginine on protein kinase C of isolated pulmonary arterial rings from rats with hypoxia-induced pulmonary hypertension |
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Authors: | YANG Hui XU Yong-jian ZHANG Zhen-xiang |
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Institution: | Respiratory Department, Tongji Hospital, Tongji Medical University, Wuhan 430030, China |
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Abstract: | AIM: To elucidate whether the mechanism that L-arginine can relieve hypoxia pulmonary hypertension involves inhibition of the activity of protein kinase C(PKC).METHODS: Twenty-one male Wistar rats were randomly divided into NS control, hypoxia and L-arginine(500 mg·kg-1·d-1, ip) treatment groups. After two-weeks treatment, mean pulmonary artery pressure (mPAP), mean systematic artery pressure (mSAP) and the ratio of the weight of right ventricle to that of left ventricle plus septum were measured, then two pulmonary arterial rings were isolated to be exposed to PDBu(a specific activator of PKC ) and observed: (1) The maximal response (P1) to 500 nmol/L PDBu, the time required to achieve a half-maximal response to 500 nmol/L PDBu (t1/2), the time during which the maximal response to 500 nmol/L PDBu maintained (T) and the isometric responses at different times (2, 4, 8, 12, 20, 40, 60, 80 min). The isometric response was represented as the percentage of the maximal response (P0) of the same arterial ring to 5μmol/L phenylephrine hydrochloride (P0%). (2) Dose-response curve in response to PDBu (10-11 000 nmol/L) and the dose producing a half-maximal response in the curve (EC50). RESULTS: mPAP, RV/(LV+S), P1, T and the isometric responses at 2, 4, 8, 20 min of NS control and L-arginine treatment groups were lower than those of hypoxic group respectively (P<0.05), while t1/2 and EC50 were all greater than those of hypoxic group respectively (P<0.05).CONCLUSION: The activity of PKC was augmented when rats were exposed to two-weeks normobaric hypoxia, which resulted in the increased reactivity of the isolated pulmonary arterial rings. L-arginine can inhibit the activation of PKC, which is likely part of the mechanism by which L-arginine can reduce mPAP and relieve the hypertrophy of right ventricle. |
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Keywords: | Arginine Protein kinaseC Hypertension pulmonary Pulmonary artery |
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