Sympathetic nervous system and deoxycorticosterone-saline hypertension.

We wish to comment on the article by de Champlain and Ameringen (Circ Res 31:617-628, 1972) in which they implicate the involvement of the peripheral sympathetic nervous system in the etiology of deoxycorticosterone (DOCA)-saline hypertension. In the Discussion of their article, the work of Clarke et al. (Life Sci [I] 9:1097-1108, 1970) has been misquoted. Contrary to the authors' impression, we did not investigate the effect of adrenal medullectomy on the production of this type of hypertension; in fact, we drew no conclusions as to the role of the adrenal glands. Consequently, their passage concerning the possible occurrence of adrenal-regeneration hypertension as a complicating influence in our study is without foundation. Like de Champlain and Ameringen, we also used 6hydroxydopamine (6-OH-DA) to inhibit peripheral sympathetic neuronal function; but, unlike them, we obtained no qualitative or quantitative change in the time course of the hypertension. They explained this discrepancy on the grounds that our biweekly dosage schedule of 6-OH-DA (compared with their weekly treatment) was probably too infrequent to maintain a state of efficient sympathectomy. Contrary to this assumption, we have shown that this treatment schedule does completely prevent hypertension resulting from chronic exposure to environmental stress (Smookler et al., Pharmacologist, 1971, and Smookler et al., Fed Proc, in press). Furthermore, it is important to note that their hypertensive model differed from ours, de Champlain and Ameringen used unilaterally adrenalectomized rats which were given DOCA only once a week. These differences appear to have resulted in a far less fulminating hypertension than that obtained in our rats with intact adrenals which were given DOCA daily. Thus, at the present time, the evidence for sympathetic neuronal involvement in DOCA-saline hypertension remains debatable. However, the answer to this question may be close to final resolution in view of the evidence advanced by de Champlain and Ameringen concerning the marked dependence of systemic blood pressure on adrenal catecholamine secretion following 6-OH-DA treatment. It would be highly desirable therefore to reinvestigate this form of hypertension utilizing chemical sympathectomy in conjunction with bilateral adrenal demedullation. This latter surgical technique can be accomplished with much less adrenal cortical damage than is instituted normally for the production of adrenalregeneration hypertension. Furthermore, adrenal-regeneration hypertension, should it occur, would be reflected in the appropriate control group. Finally, it should not be overlooked that DOCA-saline and adrenal-regeneration hypertension are closely allied, since both originate from the production of excessively high plasma mineralocorticoid levels.