The myogenic response is an important contributor to the vascular tone in resistance vessels. Though weak, it can be evoked in rat mesenteric arteries in the presence of noradrenalin (NA)¹. This led to speculation that receptor and/or store-operated cation channels are involved. Canonical Transient Receptor Potential (TRPC) channels are linked to G-protein activation and are candidates for receptor operated Ca2+ permeable cation channels in vascular smooth muscle cells (VSMCs). TRPC1 and TRPC6 channels are expressed and functional in mesenteric artery VSMCs^2,3. We hypothesized that upon alpha1-adrenoceptor activation, TRPC6 and/or TRPC1 channels are enabled, increasing sensitivity to heightened transmural pressure and leading to myogenic constriction. Male Wistar rats were ethically euthanized. 2nd or 3rd order branches of the superior mesenteric artery were isolated and mounted in a pressure myograph at a physiological pH (7.35-7.45; 5% CO2 / 25 mM HCO3-) and temperature. Vessel diameters were measured using Myoview software (Danish Myotechnology). At 60 mm Hg and in the presence of 2 nM neuropeptide Y, increasing concentrations of NA were added to the bath to achieve a stable vascular tone (8 – 12% under relaxed levels). A myogenic response was then evoked by increasing transmural pressure to 100 mm Hg. This was repeated in the presence of a TRPC channel inhibitor. Passive diameters were measured in a Ca²⁺ free solution for calculation of vascular tone (%). The overall effect of pressure increase in the presence of NA was an increase in the amount of vascular tone from 12.3 ± 0.7 (60 mmHg) to 17.6 ± 0.8 % (100 mmHg, P<0.001; N=46). Gd3+ (2 µM), an inhibitor of non-selective cation channels, did not substantially affect 75 mM-KCl induced vasoconstriction (7.6 ± 9.0 % inhibition; N=9), but abolished the pressure-induced increase in vascular tone: 12.7 ± 2.4 to 18.5 ± 2.7 % (control) vs. 8.9 ± 3.1 to 7.8 ± 3.3% (Gd3+) (P<0.05 vs. ctrl. at 100mm Hg; N=6). The non-specific TRPC channel blocker SKF96365 (5 µM) did not substantially affect KCl induced vasoconstriction (1.9 ± 1.4 % inhibition; N=5), but inhibited the myogenic response: 13.5 ± 1.6 to 21.6 ± 2.2 % tone (control) vs. 12.9 ± 1.5 to 14.9 ± 3.0 % tone (SKF96365) (P<0.001 vs. ctrl. at 100mm Hg; N=7). P values were calculated with paired t tests. Preliminary results using TRPC1 antibody (T1E3⁴, 1:250) show no significant blocking effect on the myogenic response in arteries incubated overnight with antibody (9.6 ± 0.8 to 16.2 ± 1.8% tone; N=4) compared to arteries incubated with inactivated (boiled) antibody (8.7 ± 0.7 to 16.4 ± 1.6 % tone; N=4). These results suggest that TRPC6 channels are involved in evoking myogenic responsiveness in rat mesenteric artery. Future experiments, possibly utilizing siRNA mediated TRPC6 knockdown, could elucidate this role of TRPC6 channels.