ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of tanshinone II(A) on the expression of different components in the renin-angiotensin system of left ventricles of renal hypertensive rats.</p><p><b>METHOD</b>The renal hypertension model was established in rats by the two-kidney-one-clip (2K1C) method. In the experiment, all of the rats were randomly divided into four groups (n = 15 per group) before the operation: the sham-operated (Sham) group, the hypertensive model (Model) group, the low-dose tanshinone II(A) group and the high-dose tanshinone II(A) group. At 5 week after the renal artery narrowing, the third and fourth groups were administered with 35 mg kg(-1) x d(-1) and 70 mg x kg(-1) x d(-1) of tanshinone II(A), respectively. The blood pressure in rats was determined by the standard tail-cuff method in each week after the operation. After the drug treatment for 8 weeks, all the rats were put to death, and their left ventricles were separated to determine the ratio of left ventricle weight to body weight (LVW/BW), the myocardial collagen content, and the expressions of different components in myocardial RAS, including angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin 1-type receptor (AT1R), Mas receptor mRNA expression and angiotensin II (Ang II) and angiotensin (1-7) [Ang (1-7)] content.</p><p><b>RESULT</b>Compared with the sham group, the hypertensive model group exhibited a markable increase in the content of Ang II and Ang (1-7) and the mRNA expressions of ACE, ACE2, AT1R and Mas (P < 0.01). However, the treatment with tanshinone II(A) showed the does dependence, inhibited left ventricle hypertrophy, decreased myocardial Ang II content and the mRNA expression of ACE and AT, R in renal hypertensive rats (P < 0. 01) , further increased the myocardial Ang (1-7) content and the mRNA expression of ACE2 and Mas (P < 0.01) , but without any change in the blood pressure of hypertensive rats.</p><p><b>CONCLUSION</b>The treatment with tanshinone II(A) could inhibit left ventricle hypertrophy of renal hypertensive rats. Its mechanism may be partially related to the expression of different components in the renin-angiotensin system for regulating myocardial tissues.</p>
Subject(s)
Animals , Humans , Male , Rats , Angiotensin I , Genetics , Metabolism , Angiotensin II , Genetics , Metabolism , Blood Pressure , Abietanes , Heart Ventricles , Metabolism , Hypertension , Drug Therapy , Genetics , Metabolism , Peptide Fragments , Genetics , Metabolism , Peptidyl-Dipeptidase A , Genetics , Metabolism , Rats, Sprague-Dawley , Renin , Genetics , Metabolism , Renin-Angiotensin SystemABSTRACT
<p><b>OBJECTIVE</b>To investigate the molecular and functional changes in L-type Ca2+ channel of hypertrophied cardiomyocytes in neonatal rats induced by angiotensin II (Ang II).</p><p><b>METHODS</b>The in vitro model of cardiomyocyte hypertrophy was established in cultured cardiomyocytes from neonatal rats. Whole cell patch clamp was used to measure the L-type Ca2+ currents. Semi-quantitative RT-PCR was used to determine the mRNA expression of L-type Ca2+ channel alpha1C subunits.</p><p><b>RESULTS</b>In the hypertrophied cardiomyocytes induced by Ang II, I(Ca, L) densities were increased, whereas the features of I(Ca,L) activation, inactivation or recovery from inactivation were not affected. Meanwhile, Ang II increased the mRNA expression of L-type Ca2+ channel alpha1C subunits in cardiomyocytes. All these actions of Ang II could be blocked by the angiotensin II 1 type receptor blocker losartan.</p><p><b>CONCLUSION</b>During cardiomyocyte hypertrophy induced by Ang II, there are significant changes in the molecule and function of L-type Ca2+ channels, which are mediated by the angiotensin II 1 type receptor.</p>