Characterization of the peripheral action of neurokinins and neurokinin receptor selective agonists on the rat cardiovascular system.
Abstract
The effects on mean arterial pressure (MAP) and heart rate (HR) of increasing doses (0.65-65 nmol/kg) of substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and selective agonists for neurokinin receptors were measured after intravenous (i.v.) injection in urethane anaesthetized rats. Neurokinins (NKs) elicited a vasodepressor effect with the following rank order of potency: SP (100%) greater than NKB (17.5%) greater than NKA (10%). The two undecapeptide NK-1 selective agonists, [Pro9, Met(O2)11]SP (787%) and [Sar9, Met(O2)11]SP (697%), evoked a significantly (P less than 0.05) greater vasodepressor response than SP, while the potency of the octapeptide NK-1 selective agonist [beta-Ala4, Sar9, Met(O2)11]SP (4-11) (316%) was not significantly different from SP. Conversely, the NK-2 selective agonist NKA (4-10) (less than 2%) caused only a small effect. The vasodepressor effect elicited by [MePhe7]NKB (112%) and [beta-Asp4, MePhe7]NKB (4-10) (92%), two NK-3 selective agonists, were not significantly different from that of SP. Senktide (1,095%) is the most potent NK-3 agonist, and is significantly (P less than 0.01) more potent than SP. No cross-desensitization, of the vasodepressor response, was observed between NK-1 and NK-...Continue Reading
Citations
Neurokinins produce selective venoconstriction via NK-3 receptors in the rat mesenteric vascular bed
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