Specific response of mouse tumor-feeding arterioles to stimulation by 5-HT 1 agonists

Abstract

Using intravital microscopy, we compared the responses to 5-HT 1 receptor stimulation by the host-modified arterioles feeding a Meth-A tumor implanted in the flank of female Balb c mice with the responses of tumor-independent arterioles (TIA) and those of control arterioles from mice without tumor. Topical administration of 5 × 10 −5 M serotonin in the presence of 10 −4 M ketanserin (5-HT 2 receptors inhibitor) induced arteriolar vasodilation in TIA (+13%) and in the control arterioles (+19%), but induced constriction (−14%) in the tumor-feeding arterioles (TFA). Topical administration of the general 5-HT 1 agonist 5-carboxamidotryptamine maleate (10 −6 to 10 −4 M) or the 5-HT 1A agonist buspirone (2 × 10 −6 to 2 × 10 −4 M) induced vasoconstriction that was dramatically higher in TFA than in TIA or control arterioles ( p < 0.0001 in both cases). In addition, topical administration of the 5-HT 1B agonist M-trifluoromethylphenylpiperazine (2 × 10 −6 to 2 × 10 −4 M) produced opposite responses, i.e., dose-dependent vasodilation in TIA and control arterioles, and dose-dependent constriction in TFA. Since we observed the same degree of vasodilation in response to 10 −4 M acetylcholine in all three groups of arterioles, the differences between the responses to 5-HT 1 receptor stimulation were not due to the absence of endothelial-dependent dilatory mechanisms in the tumor-feeding arterioles. We conclude that 5-HT 1 agonists are interesting pharmacologic tools for the modulation of tumoral blood flow, since they more dramatically constrict the microvasculature feeding the tumors than that feeding normal tissue.