The area postrema in deoxycorticosterone-salt hypertension in rats.

Abstract

SUMMARY Ablation of the area postrema in rats prevents sustained hypertension during angiotensin II infusion and after unilateral renal artery constriction (two-kidney, one clip hypertension). The current experiment was performed to determine whether an intact area postrema is required for hypertension development in a low renin model of experimental hypertension in rats. In 11 rats, the area postrema was destroyed using electrical current; the extent and specificity of each lesion was confirmed later by blind histological analysis. In 12 rats, sham operations were performed. All rats were uninephrectomized and drank saline. During once-weekly injections of deoxycorticosterone pivalate (5 mg/wk) for 4 weeks, sham-operated rats (n = 10) showed a significant increase in mean arterial pressure (Days 6-28) and saline intake (Days 12-28), but no significant increase in sodium or water retention. Deoxycorticosterone-treated rats with area postrema ablation (n = 9) exhibited no change in arterial pressure, sodium retention, or water retention, but a significant increase in saline intake (Days 17-28). Plasma renin activity was equally suppressed in both groups of rats. The depressor response to ganglion blockade with hexamethonium (20 mg/kg i.v.) was significantly increased during the 2nd, 3rd, and 4th weeks of steroid treatment in sham-operated, but not area postrema-ablated, rats. Four rats (2 sham-operated; 2 ablated) showed no change in any variable over 28 days in the absence of steroid treatment. It is concluded that the area postrema may be important in some non-angiotensin-dependent forms of experimental hypertension, possibly by affecting neurogenic control mechanisms. (Hypertension 9 [Suppl III]: III-206-III-209, 1987) KEY WORDS • area postrema • mineralocorticoid hypertension • arterial pressure • rat T HE area postrema (AP) is a small, highly vascular structure at the caudal end of the fourth cerebral ventricle on the dorsal medulla. The permeability of this brain structure to blood-borne substances and its substantial connectivity to other brain regions known to be important in neural cardiovascular regulation 1 make it a likely site for integration of hormonal and neural signals involved in maintaining cardiovascular homeostasis. Detailed studies by Barnes and colleagues 2 have established that the AP in the dog can be activated by acute increases in circulating angiotensin II (ANG II) so as to cause a sympathetically mediated increase in arterial pressure. In the rat, on the other hand, it was reported that the AP did not partici-

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

“…Brain lesioning studies have shown that the central nervous system may play a role in 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.…”

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

“…3 These data suggest that APX may interfere with an action of DOC-salt to modulate sympathetic outflow.…”

“…Details and results of this protocol have been described previously. 3 Four treatment groups of rats were studied: APX, DOC-salt; sham lesion, DOC-salt; APX, control; and sham lesion, control (n = 5/group).…”

“…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.…”

“…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 changes in vascular reactivity in response to DOC-salt treatment. The purpose of the current study was to determine whether discrete ablation of the AP in rats (which has been shown to prevent DOC-salt hypertension) 3 would prevent the development of changes in vascular reactivity in response to DOC-salt treatment.…”