Histamine-induced contraction and its potentiation by neuropeptide Y were investigated in rat blood vessels. Rat arteries and veins constricted with single concentrations of histamine dose-dependently (0.1-100 microM). This histamine-induced contraction immediately desensitized. Histamine H1 receptor antagonists, 1 microM mepyramine and 1 microM diphenhydramine, abolished this transient contraction completely, whereas cimetidine, phentolamine, reserpine and tetrodotoxin failed to inhibit the contraction. Histamine H1 receptor mRNA level by reverse transcription-polymerase chain reaction was quite parallel to histamine H1 receptor-mediated contraction, indicating that the contraction is mediated through histamine H1 receptors in the smooth muscle. Neuropeptide Y (10 nM in arteries and 3 nM in veins, respectively) significantly potentiated histamine H1 receptor-mediated contraction via neuropeptide Y1 receptors in most of rat blood vessels. Since the phospholipase C inhibitors, neomycin (1 mM) and 2-nitro-4-carboxyphenyl-N, N-diphenylcarbamate (NCDC, 10 microM), respectively, specifically abolished the potentiation, the potentiation by neuropeptide Y may depend on activation of phospholipase C.