Vasodilator effects of sarafotoxins and endothelin-1 in spontaneously hypertensive rats and rat isolated perfused mesentery.
Sarafotoxins (SRTa, SRTb and SRTc) and ET-1 produced a potent vasodilator effect in spontaneously hypertensive rats in vivo and in rat isolated perfused mesenteries in vitro. Among these peptides SRTc demonstrated the most potent vasodilator activity, and was three times more active than SRTa in both preparations. These peptides induced endothelium-dependent vasodilatation in vitro and pretreatment with methylene blue inhibited this effect, while exposure to the antagonists of other vasodilators did not. In contrast, [nitrophenylsulfenylated Trp21]SRTc, SRTc(1-18) and reduced and S-carboxymethylated SRTc caused no vasodilatation in either animal model; the vasodilator effect of acetylated SRTc was less potent than that of SRTc. These results suggest that (i) the vasodilatations of these peptides may be exerted through the release of endothelium derived relaxing factor; (ii) the C-terminal Trp21 and disulfide bonds are essential; and (iii) the N-terminal amino group plays an important role in vasodilator activity.
Kitazumi
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Shiba
T
T
Nishiki
K
K
Furukawa
Y
Y
Takasaki
C
C
Tasaka
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects*; D008642:Mesenteric Veins / Q000187:drug effects*; D008969:Molecular Sequence Data; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D014757:Viper Venoms; C057354:sarafotoxins s6