title: Cocaine and the porcine coronary microcirculation: effects of chronic cocaine exposure and hypercholesterolemia.
abstract: OBJECTIVE
  To examine the acute effect of cocaine on the coronary microcirculation and whether chronic cocaine administration with or without a concomitant high-cholesterol diet affects beta-adrenoceptor and endothelial functions in the coronary microcirculation.
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  Laboratory and animal research facility.
  
  
  METHODS
  Yorkshire pigs.
  
  
  METHODS
  Pigs were fed a high (2%)-cholesterol diet or a regular diet for 3 months. Animals in both groups received cocaine chronically (7 mg/kg/day, IM). Control animals were fed a regular diet.
  
  
  RESULTS
  Responses of the porcine coronary arterioles (90 to 190 microns in diameter) were examined in vitro in a pressurized (40 mmHg) no-flow state using a video-imaging apparatus. Acute application of cocaine caused a significant contraction with a mean maximal diameter decrease of 14% +/- 5%, which was markedly reduced by muscarinic blockade but not significantly affected by alpha 1-adrenergic blockade. Lidocaine or procainamide had no vasoconstrictor effect. Chronic exposure of animals to cocaine diminished contractile responses to cocaine and reduced relaxation responses to the nonselective beta-adrenergic receptor agonist isoproterenol. Phenylephrine caused a minimal (< 4%) contraction of vessels in all groups. Chronic cocaine administration with concomitant high-cholesterol feeding attenuated endothelium-dependent relaxations to serotonin, whereas endothelium-dependent relaxations to bradykinin were unaffected. Endothelium-independent relaxations to sodium nitroprusside were similar in all groups.
  
  
  CONCLUSIONS
  These results suggest that cocaine can exert a direct vasoconstrictor effect on the porcine coronary microcirculation via a muscarinic mechanism. Chronic exposure to cocaine significantly decreases beta-adrenoceptor-mediated relaxation and blunts endothelium-dependent relaxation to a small degree.
authors.affiliation: Department of Surgery, Beth Israel Hospital, Boston, MA 02215, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.forename: B D
authors.initials: BD
authors.lastname: Nunez
authors.forename: J P
authors.initials: JP
authors.lastname: Morgan
authors.forename: H B
authors.initials: HB
authors.lastname: Dai
authors.forename: J N
authors.initials: JN
authors.lastname: Ross
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001920:Bradykinin / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007273:Injections, Intramuscular; D007545:Isoproterenol / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011342:Procainamide / Q000494:pharmacology; D011446:Prospective Studies; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D014661:Vasoconstriction; D014741:Video Recording
chemical_list: D000317:Adrenergic alpha-Antagonists; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D010656:Phenylephrine; D012701:Serotonin; D008012:Lidocaine; D003042:Cocaine; D011342:Procainamide; D007545:Isoproterenol; D001920:Bradykinin