Characterization of agonist-induced endothelium-dependent vasodilatory responses in the vascular bed of the equine digit

The role of endothelium-derived relaxing factors was studied in the regulation of vascular responses in the Krebs perfused equine isolated digit. Perfusion pressure was recorded in response to bolus doses of 5-hydroxytryptamine (6 nmol) alone or co-administered with carbachol (CCh; 0.2 mu mol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 mu mol). N-omega-Nitro-L-Arginine methyl ester hydrochloride (L-NAME; 300 mu M) caused partial but significant inhibition of CCh-induced vasodilatory response, whereas BK and SP-induced responses were resistant to L-NAME. High potassium (K+, 30 mM) and the cytochrome P-450 (CYP) epoxygenase inhibitor, clotrimazole (10 mu M) plus L-NAME (100 mu M), completely abolished the CCh, BK and SP-induced vasodilatory responses, whereas the response to SNP was unaffected. In contrast, the L-NAME-resistant proportion of CCh, BK and SP-induced vasodilatory response was not inhibited by the highly selective CYP2C9 inhibitor, sulphaphenazole (10 mu M). The cyclo-oxygenase inhibitor, ibuprofen (10 mu M) did not affect the CCh, BK and SP-induced responses. These data demonstrate that CCh, BK and SP-induced relaxation in the equine digit involve a combination of the NO and endothelium-derived hyperpolarizing factor (EDHF) pathways. These results do not support the evidence for the involvement of CYP-derived epoxyeicosatrienoic acids and the exact nature of EDHF in the equine digit remains to be established

Upstream stimulating factors: highly versatile stress-responsive transcription factors

International audienceUpstream stimulating factors (USF), USF-1 and USF-2, are members of the eucaryotic evolutionary conserved basic-Helix-Loop-Helix-Leucine Zipper transcription factor family. They interact with high affinity to cognate E-box regulatory elements (CANNTG), which are largely represented across the whole genome in eucaryotes. The ubiquitously expressed USF-transcription factors participate in distinct transcriptional processes, mediating recruitment of chromatin remodelling enzymes and interacting with co-activators and members of the transcription pre-initiation complex. Results obtained from both cell lines and knock-out mice indicates that USF factors are key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism, and in melanocytes USF-1 has been implicated as a key UV-activated regulator of genes associated with pigmentation. This review will focus on general characteristics of the USF-transcription factors and their place in some regulatory networks