Trans-generational effect of maternal obesity on the programming of hypertension: Altered leptin signalling pathway in the central nervous system

The psychological stress such as air-jet stress causes pressor response and tachycardia. The stress-induced response is mediated via the dorsomedial hypothalamic area (DMH). In addition, activation of serotonin 5-hydroxytryptamine-1A (5-HT1A) receptors in the central nervous system suppress the stress-induced autonomic response, though the central pathway of the response is still unclear. In this study, we investigated that effect of microinjection of 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) into the DMH on the cardiovasular response evoked by disinhibition (activation) of the DMH nurons. Microinjection of bicuculline (BIC), GABAa receptor antagonist, in the DMH caused significant increases in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RNA) and these increases gradually returned to the pre-BIC injection level (30-40 min). At approximately 10 min after the BIC injection, all recording parameters plateaued at the peak, and then microinjection of 8-OH-DPAT was made into the same site of the BIC injection. Soon after the 8-OH-DPAT injection, the tachycardic response elicited by the DMH activation showed quicker reduction compare to the control BIC response. In contrast, the 8-OH-DPAT in the DMH did not affect the pressor and sympathoexcitatory responses to the DMH activation. The results indicate that activation of 5-HT1A receptors located in the DMH inhibits the tachycardia evoked by stimulation of neurons in the DMH.