Organ culture of arteries is generally thought to affect the contractile phenotype, but the mechanism behind this effect is not understood. In view of the reported plasticity of TRPC expression (Bergdahl et al. 2005), we have explored the changes in calcium signal, in contractility and in TRPC expression evoked by organ culture in rat resistance mesenteric artery. TRPC1 and TRPC6 were the most abundant isoforms expressed in mesenteric artery. In arteries cultured for 2 days, TRPC1 mRNA expression decreased by 47 ± 8 % (n=4, P<0.01), while TRPC6 mRNA expression increased by 94 ± 26 % (n=4, P<0.05) in comparison with non-cultured arteries. Immunofluorescence analysis of protein expression by confocal microscopy confirmed the upregulation of TRPC6 proteins after 2 days of organ culture, compared with freshly isolated mesenteric arteries. Measurement of contractile responses to cumulative concentrations of noradrenaline showed that cultured arteries were significantly more sensitive to noradrenaline than freshly isolated control arteries (pD2 values of noradrenaline were 5.83± 0.05 and 6.13 ± 0.05 n=18, in freshly isolated artery and after 48h of culture, respectively, P<0.01) Neither maximum contraction nor contraction evoked by KCl depolarization were modified. Simultaneous measurement of intracellular calcium concentration and tension in fura-2 loaded mesenteric arteries indicated that the increased sensitivity of noradrenaline-evoked contraction in cultured arteries was associated with a parallel increase in calcium signal. The increased contractile response of cultured arteries to noradrenaline was abolished in the presence of the tyrosine kinase inhibitor genistein (noradrenaline pD2 values in the presence of genistein were 5.70 ± 0.20 and 5.70 ± 0.10, n=6, in freshly isolated and cultured arteries, respectively), or of PP2, a Src kinase inhibitor (noradrenaline pD2 values in the presence of PP2 were 5.70 ± 0.10 and 5.80 ± 0.11, n=6, in freshly isolated and cultured arteries, respectively). Inhibition of protein kinase C with Gö6976, or GF109203X did not affect the contraction induced by noradrenaline either in cultured or in freshly isolated mesenteric arteries. These results indicate that organ culture of rat mesenteric resistance artery modifies TRPC expression and results in Src kinase-dependent increase in contractile response to noradrenaline.