Cimetidine inhibits the hypoxia-induced increase in cerebral blood flow in dogs

Effect of the H1 blocker d‐chlorpheniramine on cerebral blood flow in the conscious dog during normocapnic hypoxia

“…In isolated human arteries, histamine acts predominantly as a vasodilator. We have shown that cimetidine and other H 2 blockers blunt the hypoxia-induced increase in cerebral blood¯ow in the conscious dog (Clozel et al, 1985;Audibert et al, 1991). We have shown that cimetidine and other H 2 blockers blunt the hypoxia-induced increase in cerebral blood¯ow in the conscious dog (Clozel et al, 1985;Audibert et al, 1991).…”

“…This effect depends upon H 2 receptors (Gross, 1984), but, using chlorpheniramine, Toda (1990) was able to show that the in vitro blockade of H 1 receptors reduced the vasodilatation induced by histamine. We have shown that cimetidine and other H 2 blockers blunt the hypoxia-induced increase in cerebral blood¯ow in the conscious dog (Clozel et al, 1985;Audibert et al, 1991). The purpose of this Ó1998 Blackwell Science Ltd · Clinical Physiology 18, 1, 27±33 27 ............................................................................................................................................................................................................................................................................................................................ study was to assess the effect of d-chlorpheniramine, an H 1 blocker, on the hypoxia-induced increase in cerebral blood¯ow (CBF) in the awake dog.…”

“…Histamine acts on target cells in the mammalian brain via stimulation of two classes of receptors, H 1 and H 2 . The role of H 2 receptors is demonstrated in vivo, as the rise in CBF during hypoxia is blunted by cimetine, a H 2 receptor-blocking drug (Clozel et al, 1985) as well as by other H 2 blockers (Audibert et al, 1991). Histamine receptors H 1 and H 2 have been found in the cerebral arteries of the cat (Edvinsson et al, 1983), the rabbit (Sercombe et al, 1986), the dog (Toda et al, 1985) and in man (Ottosson et al, 1988).…”

“…H 1 receptors are involved in human, cat and rabbit cerebral arteries (Ottosson et al, 1988;Toda, 1990). In the dog, it is probable that the H 2 receptors dominate over the H 1 receptor in the mechanism of cerebral artery relaxation to hypoxia, because the H 2 blockers completely blunt the rise of CBF under these circumstances (Clozel et al, 1985;Audibert et al, 1991). In the dog, it is probable that the H 2 receptors dominate over the H 1 receptor in the mechanism of cerebral artery relaxation to hypoxia, because the H 2 blockers completely blunt the rise of CBF under these circumstances (Clozel et al, 1985;Audibert et al, 1991).…”

“…The in¯uence of histamine on CBF during hypoxia remains unclear. The role of H 2 receptors is demonstrated in vivo, as the rise in CBF during hypoxia is blunted by cimetine, a H 2 receptor-blocking drug (Clozel et al, 1985) as well as by other H 2 blockers (Audibert et al, 1991). However, the roles of H 1 and H 2 receptors are controversial.…”