Glibenclamide-sensitive hypotension produced by helodermin assessed in therat

The effects of helodermin, a basic 35-amino acid peptide isolated from the venom of a lizard salivary gland, on arterial blood pressure and heart rate were examined in the rat, focusing on the possibility that activation of A TP sensitive K+ (K-ATP) channels is involved in the responses. The results were also compared with those of vasoactive intestinal polypeptide (VIP). H elodermin produced hypotension in a dose-dependent manner with approximatel y similar potency and duration to VIP. Hypotension induced by both peptides was significantly attenuated by glibenclamide, which abolished a leveromak alim-produced decrease in arterial blood pressure. Oxyhemoglobin did not af fect helodermin-induced hypotension, whereas it shortened the duration of a cetylcholine (ACh)-produced hypotension. These findings suggest that helode rmin-produced hypotension is partly attributable to the activation of glibe nclamide-sensitive KS channels (li,, channels), which presumably exist on a rterial smooth muscle cells. EDRF (endothelium-derived relaxing factor)/nit ric oxide does not seem to pig an Important role in the peptide-produced hy potension.