Hypotensive effect of 13-hydroxylinoleic acid in the rat: mediation via the release of a CGRP-like mediator from capsaicin-sensitive nerves.
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 micrograms kg-1) had no direct effect on blood pressure in the rat and had no effect on histamine (0.1 - 1000 micrograms 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 micrograms kg-1) or after a dose-response curve of histamine (0.1 - 1000 micrograms kg-1). 3. This hypotensive effect of 13-HODE was not observed after administration of the endothelium-dependent vasodilator, acetylcholine (0.1 - 10 micrograms kg-1), the endothelium-independent vasodilator, sodium nitroprusside (0.1 - 100 micrograms kg-1) or the inflammatory mediator, leukotriene B4 (0.1 - 300 micrograms kg-1). However, prior injection of bradykinin (0.1 - 100 micrograms 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 micrograms kg-1 min-1), an inhibitor of excitatory effects on sensory nerves, and the CGRP antagonist, CGRP8-37 (1-3 micrograms 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.
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
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D
van Heuven-Nolsen
T
T
Muis
F
F
Engels
P A
PA
Henricks
T L
TL
Buckley
F P
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Nijkamp
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology
D008041:Linoleic Acids; D012430:Ruthenium Red; D009599:Nitroprusside; D007975:Leukotriene B4; C042835:13-hydroxylinoleic acid; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D002211:Capsaicin; D001920:Bradykinin