ROLE OF PRESYNAPTIC BETA(2)-ADRENERGIC FACILITATION IN THE DEVELOPMENT AND MAINTENANCE OF DOCA-SALT HYPERTENSION

The present study evaluated the contribution of the presynaptic beta(2 )-adrenergic facilitation in the increase of plasma norepinephrine lev els observed in deoxycorticosterone acetate (DOCA)-salt hypertension. Epinephrine is thought to be the major endogenous activator of this pr esynaptic mechanism and although basal epinephrine levels were similar in normotensive and DOCA-salt hypertensive rats, the sensitivity of t he presynaptic beta(2)-adrenergic facilitatory mechanism was found to be increased in hypertensive animals. This was shown in vivo by the en hanced plasma norepinephrine increases induced by a direct presynaptic stimulation with a selective beta(2)-adrenergic receptor agonist. Fur thermore, the adrenal medulla was hyperreactive in response to a hemor rhagic hypotension of 50 mm Hg, as shown by a greater plasma epinephri ne increase in DOCA-salt-treated rats, and tissue concentrations of ep inephrine were found to be greatly increased in the aorta of hypertens ive animals. The possible contribution of epinephrine activation of th e presynaptic beta(2)-adrenergic mechanism on the development and main tenance of DOCA-salt hypertension was assessed by evaluating the effec ts of chronic or acute adrenalectomy, respectively Acute adrenalectomy decreased significantly the blood pressure only in hypertensive anima ls, whereas chronic adrenalectomy abolished the plasma norepinephrine and blood pressure differences between normotensive and DOCA-salt-trea ted rats. The present results therefore suggest that the presynaptic b eta(2)-adrenergic facilitation is exaggerated in DOCA-salt hypertensio n, mainly due to an increased sensitivity of this mechanism and to a h yperreactivity of the adrenal medulla. Such alterations in this presyn aptic facilitatory mechanism could contribute to an increase in circul ating norepinephrine levels, which have been associated with the blood pressure elevation in this experimental model of hypertension.