Our laboratory has previously reported that plasma histamine levels ri
se significantly and coincidentally with the onset oi the decompensato
ry phase of isobaric hemorrhagic shock in rats. The histamine levels s
een in shock were comparable to those that induce profound vasodilatat
ion in many vascular beds under normovolemic conditions. We, therefore
, sought to determine whether the elevation in plasma histamine contri
butes to the cardiovascular collapse seen in the decompensatory phase
of hemorrhagic shock. Sprague-Dawley rats were bled according to an is
obaric bleeding protocol which maintained the mean arterial blood pres
sure (MAP) at 40 mmHg until death. Selected H-1 (diphenhydramine) and/
or H-2 (cimetidine and famotidine) antagonists were administered at 75
% of the estimated peak shed blood volume (PSBV), a point preceding th
e rise in plasma histamine. Plasma histamine levels in all groups were
similar throughout the time course of hemorrhagic shock. None of the
histamine receptor antagonists affected the time of onset or the rate
of decompensation, Suspecting that hypotension may alter the animal's
response to histamine, we investigated the effect of exogenous histami
ne administration on MAP before and after hemorrhage. In unbled animal
s, bolus histamine in infusions (.6 mg/kg) dropped the MAP by 62.0 +/-
2.7 mmHg, however, in animals bled to 40 mmHg, histamine dropped the
MAP by 7.2 +/- 2.7 mmHg (p = .002). On the basis of the results of the
se two interventions, we conclude that histamine is not an important m
ediator of the cardiovascular collapse seen in the decompensatory phas
e of hemorrhagic shock in the rat.