ALTERATION OF PREJUNCTIONAL ALPHA(2)-ADRENERGIC AUTOINHIBITION IN DOCA-SALT HYPERTENSION

The possible involvement of prejunctional alpha(2)-adrenergic autoinhi bition in hypertension is still controversial. The aim of this study w as 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-induce d increases in catecholamine and immunoreactive neuropeptide Y (NPY) l evels were compared between control and yohimbine (alpha(2)-adrenergic receptor antagonist) pretreated normotensive and DOCA-salt hypertensi ve rats. DOCA-salt hypertensive rats had higher basal norepinephrine l evels (NE), as well as increased NE and epinephrine (EPI) responses to a 15-mL/kg hemorrhage as compared to control normotensive rats. In no rmotensive animals, yohimbine (0.5 mg/kg, intravenous [iv]) doubled pl asma NE, EPI, and NPY levels in basal conditions and in response to th e hemorrhage. In contrast, the same treatment had smaller or no effect on basal NE levels and on the hemorrhage-induced responses in DOCA-sa lt hypertensive rats, although basal EPI levels were increased in this group. These results therefore suggest a decreased function of the pr ejunctional 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 par t explain the hyperactivity and hyperreactivity of the sympathetic ner vous system observed in this model, and thus contribute to the elevati on of blood pressure in DOCA-salt hypertension.