Alteration of prejunctional alpha 2-adrenergic autoinhibition in DOCA-salt hypertension

The possible involvement of prejunctional alpha 2-adrenergic autoinhibition in hypertension is still controversial. The aim of this study was to determine the functional integrity of this regulatory mechanism in conscious DOCA-salt hypertensive rats, a model characterized by an increased sympathetic tone and reactivity. Basal and hemorrhage-induced increases in catecholamine and immunoreactive neuropeptide Y (NPY) levels were compared between control and yohimbine (alpha 2-adrenergic receptor antagonist) pretreated normotensive and DOCA-salt hypertensive rats. DOCA-salt hypertensive rats had higher basal norepinephrine levels (NE), as well as increased NE and epinephrine (EPI) responses to a 15-mL/kg hemorrhage as compared to control normotensive rats. In normotensive animals, yohimbine (0.5 mg/kg, intravenous [iv]) doubled plasma NE, EPI, and NPY levels in basal conditions and in response to the hemorrhage. In contrast, the same treatment had smaller or no effect on basal NE levels and on the hemorrhage-induced responses in DOCA-salt hypertensive rats, although basal EPI levels were increased in this group. These results therefore suggest a decreased function of the prejunctional alpha 2-adrenergic autoinhibitory mechanism at the level of sympathetic nerve terminals and adrenal medulla during sympathetic hyperactivity in DOCA-salt hypertension. This dysfunction could in part explain the hyperactivity and hyperreactivity of the sympathetic nervous system observed in this model, and thus contribute to the elevation of blood pressure in DOCA-salt hypertension.