title: Direct inhibitory effect of chlorpromazine on smooth muscle of the porcine pulmonary artery.
abstract: BACKGROUND
  Chlorpromazine has been widely used by anesthesiologists to take advantage of its anesthesia-potentiating and vasorelaxing actions. However, the mechanisms of vasorelaxation induced by chlorpromazine are still not fully understood.
  
  
  METHODS
  Using front-surface fluorometry of fura-2 and porcine pulmonary arterial strips, we investigated the effects of chlorpromazine on the intracellular Ca2+ concentration ([Ca2+]i) and force of vascular smooth muscle. The affinities of chlorpromazine and other neuroleptics to vascular alpha(1)-adrenergic receptors were then determined by a radio-ligand binding study.
  
  
  RESULTS
  Chlorpromazine (as much as 1 microM) inhibited both the elevation of [Ca2+]i and force in pulmonary arterial smooth muscle induced by 80 mM K+-depolarization and 1 microM norepinephrine in a concentration-dependent manner. The extent of inhibition by chlorpromazine in norepinephrine-induced contraction was much greater than that in 80 mM K+-induced contraction. In contrast, as much as 1 microM chlorpromazine had no effect on the increases in [Ca2+]i or force induced by U46619, a thromboxane A2 analogue. Chlorpromazine also had no effect on the intracellular Ca2+ release induced by U46619. In a radio-ligand displacement study, chlorpromazine, haloperidol, phentolamine, trifluoperazine, and imipramine inhibited the specific binding of [3H]prazosin to the porcine aortic membranes, in this order of potency.
  
  
  CONCLUSIONS
  Chlorpromazine induces vasorelaxation through an alpha-adrenergic blocking action as well as a calcium antagonistic action; the former action may, therefore, play a major role in chlorpromazine-induced vasorelaxation.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Sakihara
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Kanaide
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014665:Vasodilator Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium; D002746:Chlorpromazine; D009638:Norepinephrine; D011224:Prazosin