Tone-dependent responses of histamine in feline pulmonary vascular bed.
Under conditions of controlled pulmonary blood flow and constant left atrial pressure, histamine produced tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. At low, baseline PV tone, histamine produced dose-dependent increases in mean lobar arterial pressure that were antagonized by the selective histamine H1-receptor antagonist, diphenhydramine. The cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 (TxA2) receptor antagonist, SQ-29548, had no effect on these vasoconstrictor responses of histamine. After an increase in PV tone with an intralobar arterial infusion of a TxA2 mimic, U-46619, histamine produced vasodilator responses at low doses, biphasic vasodilator/vasoconstrictor responses at midrange doses, and vasoconstrictor responses at high doses. Diphenhydramine antagonized vasoconstrictor responses and the vasodilator responses of low to midrange doses and enhanced vasodilator responses of high doses of histamine at elevated PV tone. Selective H2-receptor antagonists, ranitidine and meclofenamate, and selective H3-receptor antagonist, thioperamide, did not antagonize vasodilator responses of histamine. H1- and H2-receptor antagonism was more effective in reducing the vasodilator responses of histamine at elevated PV tone than H1-receptor antagonism alone. These data support that histamine produces vasoconstrictor responses at low baseline and elevated PV tone by acting on H1 receptors that do not induce the release of vasoconstrictor prostanoids. At elevated PV tone, histamine produces vasodilation by acting on H1 receptors that are not coupled to the release of vasodilator prostaglandins and also, in part, by acting on H2 receptors.
Neely
C F
CF
Department of Anesthesia, Hospital of the University of Pennsylvania, Philadelphia 19104.
Matot
I
I
Haile
D
D
Nguyen
J
J
Batra
V
V
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D014666:Vasomotor System / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D017442:Histamine Agonists; D006633:Histamine Antagonists; D006834:Hydrazines; D017482:Receptors, Thromboxane; D008469:Meclofenamic Acid; D006632:Histamine; C045749:SQ 29548