The "Statinth" wonder of the world: a panacea for all illnesses or a bubble about to burst

After the introduction of statins in the market as effective lipid lowering agents, they were shown to have effects other than lipid lowering. These actions were collectively referred to as 'pleiotropic actions of statins.' Pleiotropism of statins formed the basis for evaluating statins for several indications other than lipid lowering. Evidence both in favour and against is available for several of these indications. The current review attempts to critically summarise the available data for each of these indications

Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients.

International audiencePrevious studies suggested that certain lipid-lowering drugs such as statins suppress ubiquinone, affect mitochondrial function, and may have deleterious effect on skeletal or cardiac muscles with potentially serious clinical consequences, especially in patients with established coronary heart disease and left ventricular dysfunction. In this double-blind study, we assessed the effects of 20 mg simvastatin (S, n = 32) or 200 mg micronized fenofibrate (F, n = 32, control group) on rest and exercise left ventricular function in hypercholesterolemic survivors of a previous Q-wave acute myocardial infarction. Left ventricular radionuclide imaging was performed at rest and during submaximal exercise and global and segmental (nine segment regional wall-motion score) ejection fractions were measured before treatment and 12 weeks later. Serum ubiquinone was reduced after treatment (p = 0.03) in the S but not the F group, whereas total and low-density lipoprotein (LDL) cholesterol were significantly reduced in both groups. Before treatment, mean global ejection fraction was 52.1+/-12.2% and 49.3+/-11.8% at rest in F and S patients, respectively, and increased (56.0+/-13.7% in F and 52.1+/-12.9% in S) at peak exercise (no difference between groups). After treatment, the increase in ejection fraction tended to be lower in S (0) than in F (+3.8%) but not significantly. However, ejection fraction at rest increased after treatment in S (p = 0.009) but not in F. Subgroup analyses indicated that the improvement in rest ejection fraction in S was essentially observed in patients with ejection fraction 40% (+1.8%). Finally, the numbers of akinetic or hypokinetic segments at rest and during exercise were not different in the two groups before and after treatment. Mean maximal exercise load (113+/-23 watts in F vs. 104+/-27 W in S before treatment) was not modified by the treatment (111+/-21 and 104+/-27 W). Thus a 12-week lipid-lowering treatment with either S or F did not negatively alter left ventricular function during exercise in dyslipidemic patients with established coronary heart disease and did not affect their ability to exercise. The improvement in left ventricular function at rest after simvastatin in patients with left ventricular dysfunction warrants confirmation in further studies with large sample size

Pharmacological and molecular evidence for kinin B(1) receptor expression in urinary bladder of cyclophosphamide-treated rats

1. In the present study, we developed an experimental model of cystitis induced by cyclophosphamide (CYP). In order to characterize des-Arg(9)-BK-induced contraction on the urinary bladder (UB) during the development of inflammation and to quantify kinin B(1) receptor gene expression using a quantitative RT–PCR technique. 2. In the presence of peptidase inhibitors captopril (10 μM), DL-thiorphan (1 μM) and DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGEPTA 5 μM), bradykinin (BK) (0.3–3,000 nM) evoked a concentration-dependent contraction of rat UB which was not different between the CYP- and vehicle-treated groups. Unlike BK, des-Arg(9)-BK (0.3–100,000 nM) did not contract UB from vehicle-treated rats but contracted vigorously bladder strips from CYP-treated rats 14, 24 and 168 h after treatment. In UB of 24 h treated rat, the pD(2) value of des-Arg(9)-BK was 7.3±0.1. 3. The cyclo-oxygenase inhibitor indomethacin (3 μM) reduced by 30% the maximal response of des-Arg(9)-BK. Both the kinin B(1) receptor antagonists des-Arg(9)-[Leu(8)]BK (10 μM) and des-Arg(10)-Hoe 140 (10 μM) produced a rightward shift of the concentration-response curve to des-Arg(9)-BK yielding pK(B) values of 6.8±0.2 and 7.2±0.1, respectively, whilst the kinin B(2) receptor antagonist Hoe 140 (1 μM) had no effect. 4. After CYP treatment, mRNA coding for the kinin B(1) receptor appeared predominantly in UB. In this organ, the induction was progressive, reaching a maximum 48 h after CYP treatment. 5. In conclusion, the present study provides strong evidence for an induction of kinin B(1) receptors in UB of CYP-treated rats. This was associated at a molecular level with an increase in mRNA expression of the gene coding for the kinin B(1) receptor. This kinin receptor displayed the whole features of a classical rat kinin B(1) receptor