A serotonin-deficient rat model of neurogenic hypertension: influence of sex and sympathetic vascular tone.

Previously we showed that a loss of central nervous system (CNS) 5-hydroxytryptamine (5-HT) (tryptophan hydroxylase 2 knockout; TPH2 -/- ) leads to hypertension in male rats during wakefulness and REM sleep. Here, we tested the hypotheses that hypertension is also revealed in female TPH2 -/- when sex hormones are controlled, and that the especially high arterial blood pressure (ABP) of male TPH2 -/- rats is due to increased sympathetic vascular tone. The ABP of females was measured specifically during proestrus or estrus and again following ovariectomy. The ABP of males was measured before and after α-adrenergic blockade. Prior to ovariectomy, the ABP of female TPH2 -/- rats was ∼3 mmHg higher than TPH2 +/+ during REM sleep while in proestrus/estrus. This difference increased to ∼9 mmHg following ovariectomy ( P = 0.047). Hypertension of female TPH2 -/- was most obvious upon the transition to rapid eye movement (REM) sleep from the previous state ( P < 0.0001). Mean arterial pressure (MAP) of male TPH2 -/- rats was ∼14 mmHg higher than male TPH2 +/+ ( P = 0.02), a difference that was eliminated by α-adrenergic blockade. Male TPH2 -/- had normal plasma levels of 5-HT, norepinephrine, and epinephrine, whereas plasma dopamine was reduced by 50% compared with TPH2 +/+ ( P < 0.0001). From these data, we conclude that: 1 ) a deficiency of CNS 5-HT leads to hypertension in males and females alike, although in females the effect is mild and possibly obscured by ovarian hormones; 2 ) hypertension in females, like males, is most apparent in REM sleep, indicating a neural origin, and 3 ) increased sympathetic vascular tone underlies the elevated ABP of TPH2 -/- rats. NEW & NOTEWORTHY We show that hypertension is evident in female 5-HT-deficient TPH2 -/- rats when sex hormones are controlled, an effect most evident upon the transition to REM sleep. In addition, our data strongly suggest that increased sympathetic vascular tone contributes to the hypertension present in this 5-HT-deficient model of neurogenic hypertension.