UC San Diego

Hypertension is associated with an increased risk for cardiovascular disease, renal failure and stroke. Recent evidence indicates a strong relationship between sleep and hypertension. Neuronal serotonin has been identified as a neurotransmitter that is involved in many processes necessary for the control of both sleep and waking. Serotonin 5HT-1A receptors have been implicated to be involved in the regulation of sleep and waking. The objective of this study is to examine the extracellular domain receptor density for serotonin 5HT-1A. The extracellular domain density of the Serotonin 5HT-1A receptor was compared between control Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR) in the hypothalamic region of the brain. Additionally, a group of animals were treated with an MMP inhibitor, doxycycline for 26 weeks. At the end of the treatment, systolic blood pressure, proteolytic activity and 5HT-1A receptors extracellular domain receptor density were measured. Immunofluorescence results showed that 5HT-1A extracellular domain receptor density is significantly lower in SHR in the hypothalamic region of the brain compared to that in WKY (p<0.05). After doxycycline treatment, the systolic blood pressure was suppressed in SHR and WKY. A significant decrease in systolic blood pressure was noted between the doxycycline treated and non -treated groups (p<0.05). After doxycycline treatment, serotonin 5HT-1A extracellular domain receptor density was significantly increased in the treated SHRs (p<0.05). These results suggest that doxycycline can increase extracellular domain receptor density