Hypertension in serotonin‐deficient male rats is associated with reduced sympathetic drive to the vasculature

Abstract

Serotonin (5‐hydroxytryptamine, 5‐HT) neurons have widespread projections to autonomic regions of the brainstem and spinal cord. However, the specific role of central 5‐HT in the autonomic regulation of arterial blood pressure (BP) is unclear. We have previously shown that in quiet wakefulness (QW) and rapid‐eye‐movement (REM) sleep, adult male rats deficient in tryptophan hydroxylase 2 (TPH2−/−), and hence lacking central 5‐HT, have increased BP compared to wild‐type (WT) controls. The BP of female TPH2−/− rats is the same as WT. The current study sought to clarify the mechanism by which a loss of central 5‐HT leads to increased BP. We hypothesized that a loss of central 5‐HT increases sympathetic vascular tone. Using femoral arterial catheters along with electroencephalography and electromyography, we confirmed the elevated BP of adult (5–8 month old) male TPH2−/− rats (n=14) compared to male WT littermates (n=17), during QW (TPH2−/−: 123 vs WT: 115 mmHg; p=0.006) and REM sleep (TPH2−/−: 128 vs WT: 117 mmHg; p=0.002), but not during non‐rapid‐eye movement sleep (NREM) (TPH2−/−: 120 vs WT: 115 mmHg; p=0.068). In contrast, the BP of female TPH2−/− rats (n=15) was the same as WT littermates (n=12) (TPH2−/−: 119, 117, 123 vs WT: 112, 113, 115 mmHg in QW, NREM and REM, respectively) (p>0.05). To determine the influence of central 5‐HT on cardiac vagal drive and sympathetic vasculature tone, we injected atropine methyl nitrate (1 mg/kg; i.v.) and hexamethonium (HEX, 30 mg/kg; i.v.) into a subset of rats (n=5 male TPH2−/− and 5 WT; n= 9 female THP2−/− and 8 WT), and measured the maximum increase in heart rate (HR) and nadir in BP, respectively, during subsequent QW. The atropine‐induced increase in HR and BP experienced by male and female TPH2−/− rats was not significantly different than in WT littermates. Unexpectedly, male TPH2−/− rats had a reduced drop in BP following HEX compared to male WT (p=0.004), a phenotype not observed in female TPH2−/− rats. Our data suggest that a loss of central 5‐HT decreases sympathetic vascular tone in males only. While the mechanism(s) that contribute to the hypertension of male TPH2−/− rats remains unresolved, the potential interaction between central 5‐HT and components of the renin‐angiotensin‐aldosterone and vasopressin systems is worth exploring.Support or Funding InformationFunding for this research was provided by an American Heart Association Scientist Development Grant (14SDG18560022; PI: KJC) and a Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (F31) to JLM.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.