Specific response of mouse tumor-feeding arterioles to stimulation by 5-HT1 agonists.
Using intravital microscopy, we compared the responses to 5-HT1 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 x 10(-5) M serotonin in the presence of 10(-4) M ketanserin (5-HT2 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-HT1 agonist 5-carboxamidotryptamine maleate (10(-6) to 10(-4) M) or the 5-HT1A agonist buspirone (2 x 10(-6) to 2 x 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-HT1B agonist M-trifluoromethylphenylpiperazine (2 x 10(-6) to 2 x 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-HT1 receptor stimulation were not due to the absence of endothelial-dependent dilatory mechanisms in the tumor-feeding arterioles. We conclude that 5-HT1 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.
Stücker
O
O
Ceron, Paris, France.
Laemmel
E
E
Teisseire
B
B
Vicaut
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000737:chemistry / Q000187:drug effects; D002273:Carcinogens; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply* / Q000139:chemically induced; D007650:Ketanserin / Q000494:pharmacology; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D002273:Carcinogens; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D008748:Methylcholanthrene; D007650:Ketanserin; D000109:Acetylcholine