Effects of nifedipine, BAY K 8644, and pertussis toxin on pressor response to sarafotoxin-b in pithed rats.
The pressor actions of sarafotoxin-b (SRTX-b) were examined in pithed rats in the presence of the calcium channel antagonist nifedipine or the calcium channel activator BAY K 8644 intraarterially (i.a.) and also after pretreatment with pertussis toxin intravenously (i.v.). SRTX-b produced dose-dependent pressor effects in the pithed rat. The diastolic blood pressure (DBP) recorded in animals treated with the vehicle was 41 +/- 1 mm Hg; administration of BAY K 8644 0.1 or 0.3 mg/kg increased DBP pressure to 50 +/- 1 and 52 +/- 1 mm Hg, respectively, whereas nifedipine 0.1 or 0.3 mg/kg decreased DBP to 39 +/- 1 and 33 +/- 1 mm Hg, respectively. The actions of SRTX-b were significantly inhibited by nifedipine, whereas BAY K 8644 potentiated the pressor actions of SRTX-b. We observed that animals pretreated with pertussis toxin 25 or 50 micrograms/kg 3 days before we conducted the experiments had significantly lower DBP as compared with saline-treated animals. Treatment with pertussis toxin caused the DBP dose-response curve to SRTX-b to be displaced to the right. These results indicate that a nifedipine-sensitive (presumably extracellular) calcium pool is partly responsible for the pressor response induced by SRTX-b. They further suggest that in vascular smooth muscle, at least in some vascular beds, SRTX-b activates a pertussin toxin-sensitive G-protein that is coupled to a receptor-operated calcium or nonspecific cation channel.
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014757:Viper Venoms; D010566:Virulence Factors, Bordetella; C057354:sarafotoxins s6; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D037342:Pertussis Toxin; D009543:Nifedipine