OS 11-02 Effect of estrogen on the change of GABA function in the vasopressin neurons of salt-dependent hypertension model rats.

OBJECTIVE: Estrogen has cardio-protective effect via several peripheral mechanism. But its action on central nervous system has not been fully investigated. Estrogen receptors are expressed in the hypothalamic magnocellular neurons, secreting vasopressin. In the male-rat models of DOCA-salt, GABA functions as an excitatory, rather than inhibitory neurotransmitter in vasopressin neurons. It might contribute to the development and maintenance of hypertension. In the current study, the effect of estrogen on central GABA action was investigated in the female rat models.

DESIGN AND METHOD: GABAergic transmission in vasopressin neurons was recorded in the supraoptic nucleus (SON) slices prepared from two different female rat models of salt-dependent hypertension (salt loading and DOCA-salt), which were subjected to: 1) sham ovariectomy (sham group), 2) bilateral ovariectomy (OVX group) or 3) estrogen capsule implantation after bilateral ovariectomy (OVX + E2 group), a week prior to the commencement of treatment for the generation of the DOCA salt models.

RESULTS: Gramicidin-perforated recordings revealed that GABA was mainly inhibitory in the vasopressin neurons of sham group, whereas it acted as an excitatory transmitter in neurons of the OVX group (Figure1A). The similar result was showed in the DOCA-salt model (Figure 1B).But GABA was mostly inhibitory in the neurons of OVX + E2 group as in the cells of sham group. These findings indicated that estrogen suppresses the change of GABAergic inhibition to excitation in the vasopressin neurons of the female salt-dependent hypertension rat models and, therefore, restrains the output of these cells. To support this idea, the effects on the BP of intravenously injected V1a vasopressin receptor antagonist (d(CH2)5[Tyr(Me)2, Ala-NH29]) were evaluated in the sham and OVX groups of DOCA-salt model rats. The decrement of BP was lesser in sham DOCA-sat than in OVX DOCA-salt group (Figure 1C).

CONCLUSIONS: Blocking of the emergence of GABAergic excitation by estrogen in hypothalamic vasopressin neurons may be one of central mechanism about cardioprotective effect of estrogen.(Figure is included in full-text article.).