Inappropriate and excessive secretion of aldosterone causes sodium and water retention, contributing to the development of resistant hypertension, even when patients do not meet the diagnostic criteria for primary aldosteronism [1]. Consequently, aldosterone could be a primary therapeutic target for the treatment of resistant hypertension. Mineralocorticoid receptor antagonists have demonstrated effectiveness in treating resistant hypertension [2]. Additionally, baxdrostat, an aldosterone synthase inhibitor, has been shown to decrease plasma aldosterone levels and blood pressure in patients with resistant hypertension [3].

Unilateral adrenalectomy has been the preferred treatment for patients with unilateral aldosterone-producing adenoma. Moreover, the efficacy of unilateral adrenalectomy in resolving hypokalemia and ameliorating hypertension in patients with drug-resistant bilateral idiopathic hyperaldosteronism (IHA) has been reported [4]. Furthermore, catheter-based adrenal artery embolization, a less-invasive procedure for debulking the adrenal gland, has demonstrated benefits in reducing blood pressure and correcting biochemical abnormalities in patients with IHA [5,6,7,8].

Spontaneously hypertensive rats (SHR) are a commonly used animal model mimicking essential hypertension and presenting target organ damage. Although the precise mechanisms underlying blood pressure elevation in SHR are not fully understood, potential factors include increased activity of the renin-angiotensin-aldosterone system, elevated sympathetic nervous system activity (SNA), abnormal renal function, endothelial dysfunction, vascular remodeling, and inflammation and oxidative stress. SHR synthesize aldosterone more actively than Wistar-Kyoto rats (WKY), their normotensive counterparts, resulting in higher plasma aldosterone levels [9]. Additionally, studies have reported that adrenalectomy significantly reduces blood pressure in SHR, while supplemental aldosterone restores hypertension in adrenalectomized SHR [10,11,12,13,14].

In this issue of Hypertension Research, Wang et al. [15] reported that unilateral adrenal ablation through anhydrous ethanol injection into the left adrenal gland successfully destroyed the left adrenal cortex and medulla in both SHR and WKY. Unilateral adrenal ablation significantly lowered the blood pressure with remarkable reductions in levels of renin, angiotensin II, aldosterone, cortisol, noradrenaline, and adrenaline in SHR but not in WKY. Moreover, this procedure significantly improved hypokalemia and cardiac, renal, and vascular remodeling and function in SHR. These findings are intriguing as they demonstrate that ethanol ablation of the adrenal gland can effectively lower blood pressure and prevent target organ damage in this hypertension model. These findings suggest that debulking the adrenal gland through ethanol ablation may hold promise as a therapeutic strategy for hypertension (Fig. 1).

Fig. 1
Fig. 1The alternative text for this image may have been generated using AI.
Full size image

Effects of chemical ablation of the unilateral adrenal gland in spontaneously hypertensive rats. Upward arrows indicate increases in the values, downward arrows indicate decreases in the values, and the number of arrows represents the degree of the change. BP blood pressure

While the possibility of compensatory increases in cortisol, aldosterone, and catecholamines by the non-ablated adrenal gland cannot be ruled out, this study showed decreased serum levels of these hormones. Therefore, it is unlikely that compensatory increases in these hormones outweigh their decreases in the ablated adrenals. The reduced serum levels of pressor hormones are expected to contribute to the blood pressure reduction following adrenal ablation. However, it remains unclear which specific pressor hormone reduction played a pivotal role, and this issue may warrant further investigation in future studies.

Notably, serum levels of renin and angiotensin II decreased in SHR after adrenal ablation. The authors speculate that this may be due to reduced catecholamine levels since catecholamines can stimulate renin release. Reduced blood aldosterone concentration may inhibit efferent renal SNA via central nervous system action, reducing renin secretion from juxtaglomerular (JG) cells in the kidney. Conversely, decreased blood aldosterone concentration may reduce the reabsorption of sodium ions (Na+) in the distal tubules of the kidneys, decreasing blood volume and increasing renin secretion from JG cells. Therefore, the mechanism underlying the reduction in serum levels of renin and angiotensin II in SHR after adrenal ablation remains unclear, necessitating further investigation in future studies.