Hepatic microvascular regulatory mechanisms. V. Effects of lodoxamide tromethamine or phentolamine-HCl on vascular responses elicited by serotonin.
Initial changes in hepatic microvasculature and carotid (arterial) blood pressure were measured in anesthetized Sprague-Dawley rats receiving an endoportal injection or topical application of serotonin alone, or in combination with selected doses of lodoxamide tromethamine or phentolamine-HCl. Although infusion of 1.0 microgram per 100 g b.w. serotonin and/or 10 micrograms per 100 g b.w. lodoxamide produced no change in arterial blood pressure, 10 or 20 micrograms per 100 g b.w. serotonin evoked hypotension within 40 sec. During this period, in vivo microscopy of transilluminated livers revealed that 1.0 or 10 micrograms per 100 b.w. serotonin elicited constriction of portal venules and sinusoids, and a significant increase in the percentage of these microvessels containing decreased cellular flow. None of these responses was antagonized by 10 micrograms per 100 g b.w. lodoxamide. Topical application of 1.0, 10, or 20 micrograms serotonin provoked constriction of sinusoids and decreased sinusoidal and central venous perfusion, but no systemic hypotension. There was no significant difference in the magnitude of responses to these doses of serotonin alone or with 0.1 microgram lodoxamide; however, 100 micrograms phentolamine potentiated responses to 1.0 microgram serotonin. Given these results, and those of previous studies indicating that equivalent doses of these antagonists block mast cell degranulation or catecholamine-induced activation of alpha receptors, it is suggested that the vascular responses are mediated directly by serotonin and not indirectly by serotonin-evoked mast cell degranulation or alpha-adrenergic stimulation. The vascular receptor(s) triggered remain(s) to be elucidated.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation / Q000187:drug effects; D009570:Nitriles; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000596:Amino Acids; D009570:Nitriles; D011942:Receptors, Adrenergic, alpha; D014325:Tromethamine; D012701:Serotonin; C022028:lodoxamide tromethamine; D010072:Oxamic Acid; D010646:Phentolamine