Gene Expression Of Kv4.2/Kv4.3 K～+ Channel Subunit And Intervention In Hypertrophic Ventricle

Systemic hypertension is associated with various heart disease.Cardiac hypertrophy is both a major adaptive response to pressure overload and important risk factor in patients with hypertension.Epidemiological studies have suggested that patients with left ventricular (LV) hypertrophy secondary to systemic hypertension are at a significantly greater risk of sudden cardiac death. Hypertrophied myocytes in experimental model animals as well as in human patients usually exhibit prolongation of action potenial duration. The calcium-independent transient outword potassium current.(Ito) is activated by depolarizing and plays a key role in controlling the amplitudes and cardiac APD. Ito contributes to phase I repolarization of action potention (AP) in myocytes. The prolongation of APD is the result of decrease in Ito density.To understand molecular mechanisms underlying cardiac remodeling, expression of myosin heavy chain isoform (B/ a -HMC) genes and voltage-gated K+ channel subunit genes was examined in ventricles of abdominal aortic coarctation SD rats. The changes of LV hemodynamic parameters and LV micopathology and submicropathology structurewere exzaminated. So we try to elucidate the effects and mechanism of cilazapril, irbesartan, low dose carvedilol and high dose carvedilol on LV remodeling regression.Pressure overload model was produced by abdominal aortic coarctation in SD rats. Male rats were divided randomly into six groups: (1)Sham-operated(A); (2)abdominal aortic banding+placebo(B); (3) abdominal aortic handing+cilazipril (C); (4) abdominal aortic banding+irbesartan (D); (5) abdominal aortic banding+low dose carvedilol (E); (6) abdominal aortic banding+high dose carvedilol (F).SD rats were anesthetized with urethane.A silver clip was permanently installed on the isolated abdominal artery.Each group had five rats.Drugs were perfused into the ratsstomaches daily after 9-week operation.Time for Treatment was 9 weeks.Caudal artery blood pressure,heart rate,whole body weight,and LV weight were measured before operation and after treatment.LV hypertrophy morpholog were determined by light and electron microscope.Total RNA was isolated from each group LV by acid phenol guanidine thiocyanate extraction, RNA concentration was determined spectrophotometrically using absorbance at 260nm and 280nm.The cDNA was obtained by reverse transcription,the gene expression of MHC and B / a -MHC were detected by semi-quantitative RT-PCR.Dig oligonucleotide 3'-end labeling probe with kv4.2/kv4.3 was obtained and blotted by hybridization in situ in each gooup freezing myocardium pathological section.The gene expression kv4.2/kv4.3 was detected by chemiluminescent detection.One step method mentioned above was extract total RNA from each group myocardium .Then we did northern blotting after checking the purity of RNA.At last we scanned the image and used a software to measure the expression.Membrane protein pellet from each group myocardium was extracted after checking the purity ,fractionated by SDS-PAGE and transferred to nitrocellulose membrane.Then we did western blotting and scanned the image.Our results showed:(l)Compared with group A,a distinct increase ratio of LV weight to boody weight(LVW/BW), systolic blood pressure (SBP), heart rate and expression of B / a -MHC mRN A were found;Compared with group B, treatment group with cilazapril, irbesartan and carvedilol significantly decreased in LVW/BW, SBP, heart rate and B / a -MHC mRNA (2)Cell malformation and array abnormality were shown by light and electron microscope in LV hypertrophy rats (3) Decreased expression of Kv4.2 and Kv4.3 channel subunit mRNA and protein in LV hypertrophy rats were detected by hybridization in situ,northern blotting and western blotting (P<0.05); but upregulation expression of Kv4.2/Kv4.3 was shown in treatment group (P<0.05) .In conclusion,our results show the upregulation expression 3 / a -MHCmRNA and downregulation of Kv4.2/Kv4.3 channels in rat heart with LV hypertrophy. ACEL ARBand BB reverse the LV remodeling...