Cardioprotection of Shenfu preparata on cardiac myocytes through cytochrome P450 2J3

To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.

Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure

OBJECTIVE: To investigate the therapeutic effect of Astragali on sodium and water retention in aortocaval fistula-caused experimental congestive heart failure and its involved mechanisms. METHODS: In aortocaval fistula-caused chronic (5 wk), heart failure rats treated with and without Astragali 1.0 g/day intraperitoneally, changes of cardiac and renal function, renal response to atrial natriuretic peptide (ANP) were examined. Dot blot analysis was used to determine the effect of Astragali on hypothalamic arginine vasopresin (AVP) mRNA expression, and mRNA expressions of aortic and renal AVP V1a receptor, renal AVP V2 receptor and aquaporin-2 (AQP2) were simultaneously detected by RT-PCR method. RESULTS: Rats with aortocaval fistula impaired cardiac and renal functions evidenced by higher right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), lower + dP/dtmax of left ventricle, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume (UV), urinary sodium excretion (UNaV) and free water clearance (CH2O) compared with sham-operated control (P

Na,K-ATPase as a target for endogenous cardiotonic steroids:What’s the evidence?

With an exception of few reports,the plasma concentration of ouabain and mari-nobufagenin,mostly studied cardiotonic steroids(CTS)assessed by immunoassay techniques,is less than 1 nM.During the last 3 decades,the implication of these endogenous CTS in the path-ogenesis of hypertension and other volume-expanded disorders is widely disputed.The threshold for inhibition by CTS of human and rodent a1-Na,K-ATPase is~1 and 1000 nM,respectively,that rules out the functioning of endogenous CTS(ECTS)as natriuretic hormones and regulators of cell adhesion,cell-to-cell communication,gene transcription and transla-tion,which are mediated by dissipation of the transmembrane gradients of monovalent cat-ions.In several types of cells ouabain and marinobufagenin at concentrations corresponding to its plasma level activate Na,K-ATPase,decrease the[Na^(+)]i;/[K^(+)]i;-ratio and increase cell pro-liferation.Possible physiological significance and mechanism of non-canonical Na^(+)/K^(+)-depen-dent and Nai^(+)/Ki^(+)independent cell responses to CTS are discussed.

AMELIORATING EFFECTS OF CARDIOTONIC PILLS,A COMPOUND CHINESE MEDICINE ON MYOCARDIAL MICROCIRCULATORY DISTURBANCE AND MYOCARDIAL INJURY AFTER ISCHEMIA-REPERFUSION

Cardiotonic Pills(CP)is a compound preparation of Chinese medicine consisting of Salvia miltiorrhiza,Panax notoginseng and Borneol,and it has been approved in 1994by the China State Food and Drug Administration for treating ischemic angina pectoris.It has passed the Phase II clinical trials by the US Food and Drug Administration in2009,December,demonstrating its potential to prolong