Premium
Comparison of the contractile effects of endothelin‐1 and sarafotoxin S6b in goat isolated cerebral arteries
Author(s) -
Salom Juan B.,
Torregrosa Germán,
Miranda Francisco J.,
Alabadí José A.,
Alborch Enrique
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14299.x
Subject(s) - nicardipine , endothelin receptor , endothelin 1 , endothelins , endocrinology , vasoconstriction , egta , medicine , contraction (grammar) , anatomy , biology , calcium , receptor
1 The effects of endothelium‐derived endothelin‐1 and snake venom‐derived sarafotoxin S6b, peptides with striking structural and functional similarities, were examined and compared in isolated middle cerebral arteries of goats. 2 Endothelin‐1 and sarafotoxin S6b contracted cerebral arteries in a concentration‐dependent manner. The potency of endothelin‐1 (EC 50 = 4.9 (3.9–6.2) × 10 −10 m ) was about ten times higher than that of sarafotoxin S6b (EC 50 = 5.5 (4.4–6.9) × 10 −9 m ). The tension returned to basal values after repeated washings and contraction with endothelin‐1 could be reproduced. Endothelin‐1 and sarafotoxin S6b induced further contraction in arteries precontracted with prostaglandin F 2α (10 −5 m ). 3 Mechanical removal of the endothelium or incubation with indomethacin (10 −5 m ) displaced the concentration‐response curves to endothelin‐1 and, more pronouncedly, to sarafotoxin S6b to the left. The maximum response to sarafotoxin S6b was also increased by either of these two treatments. 4 Incubation in ‘nominally’ Ca 2+ ‐free medium attenuated the vasoconstrictor response to endothelin‐1 but not to sarafotoxin S6b, which was inhibited after incubation in Ca 2+ ‐free medium to which EGTA (10 −4 m ) had been added. Pretreatment with caffeine (2 × 10 −2 m ) in Ca 2+ ‐free medium abolished responses to endothelin‐1 and sarafotoxin S6b. 5 Bay K 8644 (10 −10 m , 10 −8 m ) enhanced and nicardipine (10 −10 m , 10 −8 m ) inhibited in a concentration‐dependent manner vasoconstrictor response to endothelin‐1. Response to sarafotoxin S6b was only affected by 10 −8 m Bay K 8644 or nicardipine. 6 It is concluded that endothelin‐1 and sarafotoxin S6b are potent vasoconstrictors of goat cerebral arteries, having direct effects on smooth muscle which are counteracted by the endothelium through the release of a vasodilatator substance, probably prostacyclin. Both endothelin‐1 and sarafotoxin S6b depend on extracellular Ca 2+ and on intracellular, caffeine‐sensitive Ca 2+ stores to develop vasoconstriction. However, endothelin‐1 depends to a larger extent than sarafotoxin S6b on free extracellular Ca 2+ .