The pressor response to spinal cholinergic stimulation in spontaneously hypertensive rats.
Several laboratories have demonstrated that central cholinergic stimulation in spontaneously hypertensive rats (SHR) results in an exaggerated pressor response as compared to normotensive (NT) controls. Recent studies in this laboratory have demonstrated a spinal cholinergic pressor system in the NT rat. The purpose of this study was to determine whether the pressor response to spinal cholinergic stimulation is enhanced in SHR. In freely moving rats, intrathecal injection of neostigmine or carbachol (1-5 micrograms) produced a dose-related hypertensive response in both strains of rats. While both agonists produced similar maximal increases in blood pressure in NT rats, the pressor responses to both agonists were significantly greater in SHR. The tachycardic responses to IT injection of cholinergic agonists were also significantly greater in SHR. These differences were more apparent at the lower doses where, for example, the pressor response to 1 microgram of agonist in the SHR was increased by 123% and 109% of the response in NT rats for carbachol and neostigmine, respectively. Since both direct and indirect acting agonists produced greater responses in SHR, and spinal depletion of acetylcholine did not reduce blood pressure in SHR, it is most likely that spinal cholinergic systems ascend to higher centers to elicit pressor responses. In the case of the SHR, these higher centers may be supersensitive to cholinergic stimulation.
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
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Buccafusco
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Magri
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007278:Injections, Spinal; D009388:Neostigmine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology*
D006426:Hemicholinium 3; D009388:Neostigmine; D002217:Carbachol; D000109:Acetylcholine