Hepatic microvascular regulatory mechanisms. IV. Effect of lodoxamide tromethamine and arterenol-HCl on vascular responses evoked by compound 48/80.
Changes in the hepatic microvasculature and systemic arterial blood pressure were measured in anesthetized Sprague-Dawley rats receiving an i.v. infusion or topical application of compound 48/80, lodoxamide, or arterenol. Histochemical determination of the number of Falck-Hillarp positive (serotonin containing) mast cells also was performed on sections of liver at the light microscopic level. The infusion of arterenol (0.1 mg/kg) or Ringer's solution (control) provoked a vasopressor response within 25 sec in rats rendered hypotensive 5 min previously with compound 48/80. The duration of this response was brief with arterial pressure returning to the pre-injection (hypotensive) state within 3 min following arterenol or Ringer's administration. The injection of lodoxamide (a purported inhibitor of histamine release) inhibited compound 48/80-induced hypotension at all doses except 1 mg/kg. In vivo microscopy revealed that topical administration (0.1 microgram) significantly antagonized the microvascular responses elicited by compound 48/80. However, higher doses of lodoxamide (1.0-10 micrograms) when applied topically were found to be vasoactive. Given these results and the histochemical demonstration of an inhibition of compound 48/80-induced release of serotonin, it is suggested that: lodoxamide antagonizes the action of compound 48/80 by blocking the release of mast cell constituents, and neither compound 48/80 nor the released constituents appear to modify vascular responsiveness to arterenol or hypervolemia following the initiation of hypotension.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005453:Fluorescence; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects*; D009570:Nitriles; D009638:Norepinephrine / Q000494:pharmacology*; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D000596:Amino Acids; D006634:Histamine H1 Antagonists; D009570:Nitriles; D014325:Tromethamine; D003189:p-Methoxy-N-methylphenethylamine; C022028:lodoxamide tromethamine; D010072:Oxamic Acid; D009638:Norepinephrine