Pharmacological Characterization of Vasomotor Responses in the Tree Shrew (Tupaia belangeri) Basilar Artery: A Promising Model for Human Cerebrovascular Research.

The tree shrew (Tupaia belangeri) is increasingly recognized as an important experimental model for studying human diseases due to its close phylogenetic relationship with humans. Because the basilar artery's response to endogenous vasoactive mediators varies among species, we investigated the effects of vasoactive substances on isolated tupaia basilar arteries to determine whether this species is suitable as a human model. 5-Hydroxytryptamine (5-HT) and histamine (His) induced contraction, while bradykinin (BK) and acetylcholine (ACh) produced concentration-dependent relaxation. Pharmacological analysis revealed that contractions triggered by 5-HT were regulated through 5-H1 and 5-HT2 receptors, while His-induced responses were mediated by H1 receptors. BK-induced relaxation was inhibited by the B2 antagonist HOE140 and Nω-nitro-L-arginine (L-NA), but not by B1 antagonists or indomethacin, suggesting a B2 receptor-mediated nitric oxide (NO) pathway. ACh-induced relaxation was markedly reduced in the presence of L-NA and the M3 antagonist pFHHSiD, indicating M3 receptor-mediated NO release. At basal tone, L-NA evoked a contractile response, while indomethacin led to relaxation, suggesting basal regulation by NO and prostanoids. These findings demonstrate that 5-HT1/5-HT2 and H1 receptors mediate contraction, while B2 and M3 receptors mediate relaxation in the tupaia basilar artery. This study highlights species-specific cerebrovascular regulation and supports the tupaia as a relevant model for investigating human cerebrovascular physiology and pathophysiology.