201. Hypotensive effect of 13-hydroxylinoleic acid in the rat: mediation via the release of a CGRP-like mediator from capsaicin-sensitive nerves.
- Author
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van Heuven-Nolsen D, Muis T, Engels F, Henricks PA, Buckley TL, and Nijkamp FP
- Subjects
- Acetylcholine pharmacology, Animals, Animals, Newborn, Bradykinin pharmacology, Calcitonin Gene-Related Peptide antagonists & inhibitors, Dose-Response Relationship, Drug, Histamine pharmacology, Leukotriene B4 pharmacology, Linoleic Acids pharmacology, Male, Neurons drug effects, Neurons, Afferent drug effects, Neurons, Afferent metabolism, Nitroprusside pharmacology, Rats, Rats, Wistar, Ruthenium Red pharmacology, Blood Pressure drug effects, Calcitonin Gene-Related Peptide metabolism, Capsaicin pharmacology, Neurons, Afferent physiology
- Abstract
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.
- Published
- 1995
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