Area postrema ablation and vascular reactivity in deoxycorticosterone-salt-treated rats.

Abstract

SUMMARY In rats, central administration of the neurotoxin 6-hydroxydopamine prevents hypertension and certain functional vascular changes after deoxycorticosterone (DOC)-salt treatment. In this study, the effect of electrolytic ablation of the area postrema on blood pressure and vascular reactivity in DOC-salt-treated rats was examined. Four treatment groups of rats were studied (n = 5 in each): area postrema lesion, DOC-salt (DOC pivalate, 5 mg/wk s.c. for 5 weeks); sham lesion, DOCsalt; area postrema lesion, control; and sham lesion, control. Helically cut strips of carotid artery, aorta, and mesenteric artery were prepared for isometric force recording. Area postrema lesion attenuated hypertension in DOC-salt rats (mean arterial pressure, 107 vs 123 mm Hg in area postrema lesion and sham lesion rats, respectively; chronic aortic catheter). Vascular strips from sham lesion-DOC-salt rats were more sensitive to KC1, ouabain, and serotonin than were those from sham lesioncontrol rats. These changes in vascular reactivity also were observed in area postrema lesion-DOCsalt rats. DOC treatment in rats on a normal sodium intake did not result in hypertension or increased vascular reactivity. In summary, integrity of the area postrema is necessary for hypertension, but not for changes in vascular reactivity, in DOC-salt rats. It appears that 1) changes in vascular reactivity may be necessary, but they are not sufficient to produce DOC-salt hypertension, and 2) if these vascular changes are secondary to a central nervous system effect, they are mediated by a pathway distinct from the area postrema. sion in rats.1 -2 More recently, it has been demonstrated that ablation of the area postrema (AP), a high vascular circumventricular organ in the medulla, also prevents DOC-salt hypertension in rats.3 Furthermore, central catecholamine depletion by administration of the neurotoxin 6-hydroxydopamine (6-OHDA) has been shown to prevent hypertension in this model. 4 -5 Changes in reactivity of vascular smooth muscle to vasoconstrictors have been postulated to contribute to DOC-salt, as well as many other forms, of hypertension. Interestingly, central 6-OHDA treatment prevents not only elevated arterial pressure, but also the increased vascular sensitivity to vasoconstrictors characteristic of DOC-salt hypertension.4 -6 7 Based on studies of this type, it may be hypothesized that the increase in vascular reactivity in DOC-salt hypertensive rats is not due to a direct effect of DOC-salt on the vasculature, but rather to an effect of DOC-salt on the brain. As central 6-OHDA treatment produces catecholamine depletion in many brain regions, it is not possible from these studies to identify specific areas that are involved in the genesis of hypertension or in

Vascular responsiveness in rats resistant to aldosterone-salt hypertension.

“…Vascular smooth muscle sensitivity to ah" four agonists has been demonstrated to be increased in vessels from DOC-salt hypertensive rats compared with vessels from normotensive controls. 21 In addition, norepinephrine sensitivity has been shown to be increased in aortas from aldosterone-salt hypertensive rats compared with normotensive rats. 4 In Wistar rats treated with aldosterone-salt for 4 weeks, contractile sensitivity of the carotid arteries to KG, norepinephrine, and serotonin was significantly increased, as was the sensitivity of aortas to ouabain.…”

“…37 In the whole animal, both hyper-tension and changes in vascular reactivity in response to mineralocorticoid administration depend on elevated NaCl intake because neither are observed in rats with a normal sodium intake. 21 Central administration of 6-hydroxydopamine to selectively deplete brain catecholamines prevents DOC-salt hypertension and alterations in vascular reactivity, 38 suggesting that integrity of brain structures is necessary for DOC to produce changes in vascular reactivity. In view of the uncertainties about whether mineralocorticoids act directly on vascular smooth muscle or secondary to some other mechanism in the whole animal to alter vascular reactivity, no conclusions can yet be made as to the mechanism by which WF rats are resistant to the effects of aldosterone and salt on in vitro vascular reactivity.…”

Vasopressin response in collecting ducts of rats resistant to mineralocorticoid hypertension.

“…For example, experimental lesions of the area postrema prevent hypertension 25 while leaving peripheral responses (vascular hyperreactivity) to DOCA intact. 26 Ablation of the anteroventral third ventricle 27 can abolish both the development of DOCA hypertension and the enhancement of peripheral vascular reactivity. Primary vascular changes induced by deoxycorticosterone could also give rise to hypertension.…”

Role of central mineralocorticoid receptors in cardiovascular disease

“…Mineralocorticoid and renovascular hypertension, and hypertension in the Dahl SS rat, are prevented by destruction of tissue anteroventral to the third ventricle of the brain (the AV3V area) and the area postrema, or by chemical ablation of the central sympathetic system [31][32][33]. The AV3V area is important in the processing and integration of information about fluid and electrolyte homeostasis and baroreceptor input, modulation of baro and renal reflexes, and mediation of the central pressor effects of angiotensin II [34,35].…”