Spinal cord serotonin receptors in cardiovascular regulation and potentiation of the pressor response to intrathecal substance P after serotonin depletion.
The aim of this study was to characterize, in conscious rats, the spinal cord 5-hydroxytryptamine (5-HT) receptors involved in mean arterial pressure (MAP) and heart rate (HR) regulation as well as to examine the influence of bulbospinal 5-HT fibers on cardiovascular responses to intrathecal (i.t.) substance P (SP). The i.t. injection of 5-HT or 5-carboxamidotryptamine (5-CT) (5-HT1A,1B,1D agonist) reduced MAP and increased HR in a dose-dependent manner. In contrast, the agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 5-HT1A agonist) and alpha-CH3-5-HT (5-HT1C and 5-HT2) only caused a decrease in HR, while the agonist 2-CH3-5-HT (5-HT3) was devoid of cardiovascular effects. The vasodepressor response to 5-CT was antagonized by methiothepin but not affected by mesulergine, ketanserin, propranolol, or yohimbine. However, all five antagonists reduced the HR increase to 5-CT. Ketanserin, propranolol, mesulergine, yohimbine, and methylsergide were without effect on resting MAP, while methiothepin reduced MAP. Methiothepin, ketanserin, and methylsergide increased resting HR, yet the other antagonists had no effect on this parameter. Rats treated with p-chlorophenylalanine or 5,7-dihydroxytryptamine, but not with 6-hydroxydopamine, exhibited higher resting HR than that of control rats. Although the resting MAP was unaffected, the pressor response to i.t. SP was significantly enhanced by either 5-HT toxin. The results suggest that the receptor mediating the depressor response to 5-HT and 5-CT conforms with the broad pharmacological profile of a 5-HT1-like receptor and is unlikely to be of the 5-HT2 or 5-HT3 subtype. Since the HR response evoked by 5-CT was blocked by antagonists that exhibit affinities for various 5-HT receptor subtypes, it is suggested that a nonspecific blockade or, alternatively, that more than one receptor contributes to this cardiac effect. In addition, the results raise the possibility that a spinal 5-HT input, likely mediated by 5-HT2 receptors, tonically inhibits HR. Hence, an antagonistic interaction between 5-HT and SP is proposed to play a role in the control of arterial blood pressure in the spinal cord.
Hasséssian
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Département de physiologie, Faculté de médecine, Université de Montréal, PQ, Canada.
Poulat
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Hamel
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Reader
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Couture
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003243:Consciousness; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D011985:Receptors, Serotonin; D012701:Serotonin; D013373:Substance P