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Insensitivity of calcium‐dependent endothelial stimulation in rat isolated aorta to the calcium entry blocker, flunarizine
Author(s) -
Miller R.C.,
Schoeffter P.,
Stoclet J.C.
Publication year - 1985
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.1476-5381.1985.tb08885.x
Subject(s) - flunarizine , phenylephrine , endocrinology , acetylcholine , medicine , calcium , chemistry , biology , blood pressure
1 In rat aortic segments complete with endothelium, acetylcholine (1 μM) relaxed noradrenaline, phenylephrine and prostaglandin F 2α (PGF 2α ‐induced contractions of various magnitudes. Maximal 1 μM phenylephrine‐induced contractions were relaxed to a greater extent than were maximal contractions induced by the other two agonists. 2 Contractions elicited by various concentrations of phenylephrine and PGF 2α in the presence of a maximal effective concentration of the calcium entry blocker flunarizine (3 μM) were relaxed by acetylcholine to about the same residual tension as were contractions elicited in the absence of flunarizine. 3 Acetylcholine (1 μM) and phenylephrine (1 μM) increased tissue levels of guanosine cyclic 3′5′‐monophosphate (cyclic GMP) by about 37 fold and 2 fold respectively. Preincubation of tissues in the absence of calcium abolished these agonist‐induced increases in cyclic GMP levels, but preincubation with flunarizine had no significant effect on the increase in cyclic GMP level induced by the agonists. Pretreatment with flunarizine had no significant effect on the basal tissue level of cyclic GMP, but pretreatment in calcium‐free solution reduced the basal tissue level of the cyclic nucleotide by about half. 4 It is concluded that in rat aorta, endothelium‐dependent acetylcholine‐induced relaxation and endothelium‐dependent acetylcholine and phenylephrine‐induced increases in tissue levels of cyclic GMP, are dependent on extracellular calcium, but are not antagonized by flunarizine. This may indicate that if calcium channels of endothelial cells are activated by these agonists, their characteristics are not identical with those of the calcium channels of the smooth muscle cells.