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 pu lmonary vascular (PV) bed of intact-chest, spontaneously breathing cat s. At low, baseline PV tone, histamine produced dose-dependent increas es in mean lobar arterial pressure that were antagonized by the select ive histamine H-1-receptor antagonist, diphenhydramine. The cyclooxyge nase inhibitor, meclofenamate, and the thromboxane A(2) (TxA(2)) recep tor antagonist, SQ-29548, had no effect on these vasoconstrictor respo nses of histamine. After an increase in PV tone with an intralobar art erial infusion of a TxA(2) mimic, U-46619, histamine produced vasodila tor responses at low doses, biphasic vasodilator/vasoconstrictor respo nses at midrange doses, and vasoconstrictor responses at high doses. D iphenhydramine antagonized vasoconstrictor responses and the vasodilat or responses of low to midrange doses and enhanced vasodilator respons es of high doses of histamine at elevated PV tone. Selective H-2-recep tor antagonists, ranitidine and meclofenamate, and selective H-3-recep tor antagonist, thioperamide, did not antagonize vasodilator responses of histamine. H-1- and H-2-receptor antagonism was more effective in reducing the vasodilator responses of histamine at elevated PV tone th an H-1-receptor antagonism alone. These data support that histamine pr oduces vasoconstrictor responses at low baseline and elevated PV tone by acting on H-1 receptors that do not induce the release of vasoconst rictor prostanoids. At elevated PV tone, histamine produces vasodilati on by acting on H-1 receptors that are not coupled to the release of v asodilator prostaglandins and also, in part, by acting on Hz receptors .