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Hypotensive effect of 13‐hydroxylinoleic acid in the rat: mediation via the release of a CGRP‐like mediator from capsaicin‐sensitive nerves
Author(s) -
HeuvenNolsen Dicky,
Muis Thea,
Engels Ferdi,
Henricks Paul A.J.,
Buckley Theresa L.,
Nijkamp Frans P.
Publication year - 1995
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.1476-5381.1995.tb15008.x
Subject(s) - histamine , bradykinin , capsaicin , vasodilation , chemistry , sodium nitroprusside , endocrinology , acetylcholine , medicine , pharmacology , antagonist , calcitonin gene related peptide , blood pressure , neuropeptide , nitric oxide , receptor
1 The effect of 13‐hydroxylinoleic acid (13‐HODE) on changes in blood pressure in the rat was measured. 2 13‐HODE (0.1 −100 μg kg −1 ) had no direct eifect on blood pressure in the rat and had no eifect on histamine (0.1–1000 μg kg −1 ‐induced changes in blood pressure. In contrast, it was found that 13‐HODE itself induced a decrease in diastolic arterial blood pressure when it was injected intravenously after either a single dose of histamine (10, 100 or 1000 μg kg −1 ) or after a dose‐response curve of histamine (0.1–1000 μg kg −1 ). 3 This hypotensive eifect of 13‐HODE was not observed after administration of the endothelium‐dependent vasodilator, acetylcholine (0.1–10 μg kg −1 ), the endothelium‐independent vasodilator, sodium nitroprusside (0.1–100 μg kg −1 ) or the inflammatory mediator, leukotriene B 4 (0.1–300 μg kg −1 ). However, prior injection of bradykinin (0.1–100 μg kg −1 ) allowed a dose‐dependent hypotensive effect of 13‐HODE to be revealed. 4 The hypotensive effect of 13‐HODE after histamine and bradykinin could be inhibited by neonatal capsaicin treatment of the rats (50 mg kg −1 , s.c. on day 1 and 2 after birth). 5 Ruthenium red (120 μg kg −1 min −1 ), an inhibitor of excitatory effects on sensory nerves, and the CGRP antagonist, CGRP 8.37 (1–3 μg kg −1 min −1 ) also inhibited the hypotensive effect of 13‐HODE. 6 It is concluded that the hypotensive effect of 13‐HODE in the rat after histamine and bradykinin is due to the release of a CGRP‐like substance from sensory nerves. These results highlight the possibility that endogenous 13‐HODE could be involved in the neurogenic regulation of blood pressure.