Abnormal regulation of the sympathoadrenal system in deoxycorticosterone acetate – salt hypertensive rats

Abstract

With the use of circulating norepinephrine (NE) and epinephrine (E) levels, the sympathoadrenal activity as well as its local modulation by adrenoceptors were studied in normotensive (NT) and DOCA–salt hypertensive (HT) rats. In anesthetized hypertensive rats, plasma NE levels were higher, whereas in conscious animals both NE and E levels were found to be increased, suggesting an increased basal sympathoadrenal tone in these animals. The finding of a close correlation between blood pressure levels and NE levels suggests that the elevation of blood pressure may be linked to sympathetic system activity in this experimental model of hypertension. The reactivity of the sympathoadrenal system was also found to be increased in DOCA HT rats. Following a bilateral carotid occlusion of 1 min, which specifically activates the adrenal medulla, the elevation of E levels was found to be potentiated in intact or vagotomized HT rats. Moreover, in response to prolonged or acute hypotension in anesthetized and conscious animals, the elevation in plasma NE and E levels was found to be markedly potentiated in DOCA HT rats. The local modulating adrenoceptor-mediated mechanisms of the sympathoadrenal system appeared to be altered in this model of hypertension. Although it was possible to demonstrate that the E response to carotid occlusion can be greatly potentiated by administration of an α2-antagonist (yohimbine) and completely abolished by an α2-agonist (clonidine) in NT rats, the E response was found to be unaffected by the same treatments in HT rats, suggesting a reduced sensitivity in the α2-mediated inhibitory modulation of the adrenal medulla. Moreover, the acute treatment with a β-blocker (sotalol) lowered circulating NE levels and blood pressure only in HT rats, suggesting the possibility of a more sensitive β-receptor-mediated presynaptic facilitatory mechanism on sympathetic fibers of these animals. Finally, it was observed that the functional balance which exists between the activities of sympathetic fibers and the adrenal medulla in normotensive animals appears to be impaired in DOCA HT rats. In conclusion, the present studies suggest that the increased sympathoadrenal tone and reactivity may be due, in part, to a variety of dysfunctions in local adrenoceptor modulatory mechanisms of the sympathoadrenal system in DOCA hypertensive rats.