title: Statins decrease serotonin-induced contractions in coronary arteries of swine in vitro.
abstract: Recent evidence suggests that statins improve the status of patients with coronary artery disease not only by reducing cholesterol levels, but also by acting at the level of the endothelium-smooth muscle unit. Previous results from our laboratory showed that these drugs interact with the vascular wall by partially inhibiting calcium-dependent, agonist-induced contractions in rat aortas. To evaluate whether this effect is also extended to the coronary vasculature, we assessed the effect of statins on serotonin (5-HT) induced contractions of left and right coronary arteries of swine. Concentration-response curves for the 5-HT-induced contractions (from 0.1 nmol/l to 100 micromol/l) were calculated on rings from both coronaries in the presence and absence of either (5 micromol/l) pravastatin, mevastatin, simvastatin, lovastatin, or atorvastatin. After a 45-min incubation period, all statins significantly reduced the Emax for the 5-HT-induced contractions, ranging from 51.9 +/- 1.9% (simvastatin) to 15.9 +/- 2.0% (pravastatin) in the left coronary artery and from 48.8 +/- 2.0% (simvastatin) to 17.8 +/- 2.5% (pravastatin) in the right coronary artery. The EC50 values for the 5-HT-induced contractions were 0.150 +/- 0.005 micromol/l for the left coronary artery and 0.171 +/- 0.010 micromol/l for the right coronary artery. These values significantly changed after incubation with statins, ranging from 1.240 +/- 0.101 micromol/l (for simvastatin) to 0.081+/- 0.008 micromol/l (for pravastatin) in the left coronary artery and from 1.410 +/- 0.075 micromol/l (for simvastatin) to 0.084 +/- 0.008 micromol/l (for pravastatin) in the right coronary artery. This evidence supports the possibility that, beyond their lipid-lowering properties, statins may provide a beneficial effect in atherosclerotic patients by reducing the tone in the coronary vasculature, facilitating blood flow to the myocardium.
authors.affiliation: Department of Physiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico. mcrespo@rcm.upr.edu
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Crespo
authors.forename: José A
authors.initials: JA
authors.lastname: Quidgley
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D017035:Pravastatin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C012258:mevastatin; D012701:Serotonin; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin