Role of alpha2-adrenergic receptors and cyclic adenosine monophosphate-dependent protein kinase in the regulation of norepinephrine release in the central nervous system of spontaneously hypertensive rats.

There has been much evidence showing that the central sympathetic nervous system may be involved in the control of blood pressure. In the present study, we investigated the role of the presynaptic alpha2-adrenergic receptors and the cyclic adenosine monophosphate-dependent protein kinase (protein kinase A) in the regulation of norepinephrine release in the central nervous system in hypertension. The alpha2-adrenergic receptor agonists UK 14, 304 and clonidine inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner in the medulla oblongata of Sprague-Dawley rats. Pretreatment of pertussis toxin (a potent inhibitor of the Gi-protein) attenuated the suppression of NE release by UK 14, 304. The protein kinase A inhibitor H-8 also reduced the stimulation-evoked [3H]norepinephrine release in rat medulla oblongata. In spontaneously hypertensive rats, the inhibitory effect of UK 14, 304 on the stimulation-evoked norepinephrine release was significantly less than in age-matched normotensive Wistar-Kyoto rats. By contrast, the protein kinase A inhibitor H-8 reduced the stimulation-evoked norepinephrine release to a greater extent in hypertension than in normotensive controls. The results of the present study showed that the alteration in the presynaptic alpha2-receptor-protein kinase A system might actively participate in the regulation of norepinephrine release in the central nervous system in hypertension.