Hindbrain serotonergic neurons facilitate recovery from hypotensive hemorrhage

Abstract

Central serotonin is thought to contribute to sympatholytic responses to severe hemorrhage. In preliminary attempts to identify serotonergic nuclei that mediate this effect, we noted that lesion of hindbrain serotonergic neurons had no effect on sympatholytic responses to hemorrhage in conscious rats. Here, we tested whether more global serotonergic lesions delayed the hypotensive response. Hemodynamic effects of hemorrhage (3.2 ml/kg/min for 6 min) were measured in rats injected with vehicle (n=7) or the serotonergic neurotoxin, 5,7-dihydroxytryptamine, targeted to hindbrain raphe nuclei (n=7) or to the lateral cerebral ventricle and cisterna magna (n=5) 2-weeks earlier. Caudal raphe lesions reduced tryptophan hydroxylase positive (TPOH+) cell numbers by 76% in the hindbrain, but did not alter midbrain TPOH+ cell numbers. Global lesion reduced TPOH+ cells by 71% and 90% in the hindbrain and midbrain respectively. Tyrosine hydroxylase positive cells were not affected. The hypotensive response was not delayed by either lesion type. However, recovery of blood pressure and heart rate were slower in rats with hindbrain lesions compared to controls (42 ± 4**, 62 ± 6** and 82 ± 7 vs. 60 ± 5, 85 ± 6 and 91 ± 5 mm Hg; 216 ± 23**, 251 ± 20**, 288 ± 20* vs. 268 ± 22, 320 ± 21 and 345 ± 18 bpm, 10, 15 and 20 min after start of blood withdrawal, *,**P<0.05, 0.01). A similar trend was seen after global lesion. We conclude that hindbrain serotonin neurons facilitate compensatory re-establishment of blood pressure following volume depletion. Supported by HL 0722354 and 076162.