Potentiation by D-penicillamine and other sulfhydryl agents of the vascular response to histamine in the anaesthetized dog.
D-penicillamine (80 mg/kg) potentiates the fall in blood pressure produced by an i.v. injection of histamine in the anaesthetized dog but is inactive on the effects of acetylcholine and prostaglandin E1. Other sulfhydryl agents (alpha-thioglycerol, 2-mercaptoethanol, 2,3-dimercapto-l-propanol, DL-cysteine, glutathione, diethyldithiocarbamate) can similarly modify the effects of histamine on blood pressure but two metal complexing agents (CaNa2 EDTA and orthophenantroline) are inactive. After pretreatment with indomethacin (10 mg/kg) or cimetidine (0.5 mg/kg/min) D-penicillamine still increases the effect of histamine but not after pretreatment with pyrilamine maleate (1 mg/kg). Moreover D-penicillamine does not modify the blood pressure drop due to dimaprit but increases that to 2-(2-pyridyl) ethylamine. It is concluded that D-penicillamine and some other sulfhydryl agents can increase the blood pressure lowering effects of histamine at the level of vascular H1-receptors by a sensitizing mechanism which might involve the rupture of a disulfide bridge.
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D010396:Penicillamine / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D013438:Sulfhydryl Compounds; D006632:Histamine; D010396:Penicillamine