Cf. Neely et al., TONE-DEPENDENT RESPONSES OF HISTAMINE IN FELINE PULMONARY VASCULAR BED, American journal of physiology. Heart and circulatory physiology, 37(2), 1995, pp. 653-661
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
.