Glibenclamide-sensitive hypotension produced by helodermin assessed in the rat.
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 ATP sensitive K+ (K(ATP)) channels is involved in the responses. The results were also compared with those of vasoactive intestinal polypeptide (VIP). Helodermin produced hypotension in a dose-dependent manner with approximately similar potency and duration to VIP. Hypotension induced by both peptides was significantly attenuated by glibenclamide, which abolished a levcromakalim-produced decrease in arterial blood pressure. Oxyhemoglobin did not affect helodermin-induced hypotension, whereas it shortened the duration of acetylcholine (ACh)-produced hypotension. These findings suggest that helodermin-produced hypotension is partly attributable to the activation of glibenclamide-sensitive K+ channels (K(ATP) channels), which presumably exist on arterial smooth muscle cells. EDRF (endothelium-derived relaxing factor)/nitric oxide does not seem to play an important role in the peptide-produced hypotension.
Horikawa
N
N
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Kataha
K
K
Watanabe
N
N
Ishii
K
K
Yanaihara
N
N
Tanaka
Y
Y
Shigenobu
K
K
Nakayama
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010108:Oxyhemoglobins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010108:Oxyhemoglobins; D010455:Peptides; D015221:Potassium Channels; D014660:Vasoactive Intestinal Peptide; C040442:heliodermin; D005905:Glyburide