Sleep Pattern and Serotonin 5HT‐1A Receptor Cleavage in the Brain of the Spontaneously Hypertensive Rat

Hypertension is associated with an increased risk for cardiovascular disease and there is a relationship between sleep disturbance and hypertension. Neuronal serotonin and the 5HT1A receptors mediate processes necessary in the regulation of sleep and waking. The spontaneously hypertensive rat (SHR) has a reduced quiet sleep (QS) period. We have shown that hypertension is accompanied by proteolytic extracellular receptor cleavage involving matrix metalloproteinases (MMPs). Our objective was to examine the extracellular domain density of the 5HT1A receptor in the hypothalamic region of the SHR and its control WKY. Immunofluorescence labeling with an antibody against the extracellular domain of the 5HT1A receptor showed significantly lower labeling density in the SHRs (p<0.05). A group of animals were treated with doxycycline, for 26 weeks. After treatment, the systolic blood pressure was reduced in SHR and WKY (p<0.05) and the density of the extracellular domain of the 5HT1A receptor was significantly increased in the treated SHRs (p<0.05). The treated SHRs had significantly longer duration and fewer sleep interruptions of QS than the non‐treated SHRs. These results suggest that the interrupted sleep pattern in the SHR may be associated with proteolytic serotonin receptor cleavage and MMP inhibition may increase extracellular domain receptor density and improve sleep duration. Supported by HL 10881 and NSC 96‐2628‐B‐010‐029‐MY3