Hypothyroid-induced changes in autonomic control have a central serotonergic component

Abstract

Three experiments were conducted in unanesthetized rats made hypothyroid (Hypo) or maintained as euthyroid controls (Eu) to examine general cardiovascular responsiveness [experiment I (Exp I)]; responsiveness to a serotonin (5-HT2) agonist, dl-2,5-dimethoxy-4-iodoamphetamine [DOI intracerebroventricularly; experiment II (Exp II)]; or responsiveness to a 5-HT(1A) agonist dl-8-hydroxydipropyl-aminotetralin hydrobromide [8-OH-DPAT intracerebroventricularly; experiment III (Exp III)]. In Exp I, intravenous infusions of phenylephrine and nitroprusside provided little evidence that findings in Exp II and III were caused by generalized impairment in cardiovascular responsiveness in Hypo. In Exp II and III, Eu and Hypo were given either intra-arterial atropine or vehicle. Atropine significantly elevated heart rate (Exp II and III) and mean arterial pressure (Exp II) in Eu only. When compared with Eu, Hypo had a reduced pressor response (5.2 vs. 20.1%), an attenuated pulse pressure response (19.3 vs. 35.4%), and a more robust bradycardia (-17.7 vs. -7.0%) in response to DOI. These differences were atropine sensitive. In Exp III, Hypo had larger decrements in mean arterial pressure (-9.0 vs. -5.1%), heart rate ( -13.9 vs. - 7.7%), and body temperature (-4.5 vs. -2.7%) in response to 8-OH-DPAT in comparison to Eu. Parasympathetic involvement in the differential responses to 8-OH-DPAT was less clear than with DOI. Deranged autonomic control in hypothyroidism may be caused, in part, by changes in central serotonergic activity.