A controlled trial of percutaneous adrenal arterial embolization for hypertension in patients with idiopathic hyperaldosteronism.

Our prior study has suggested that percutaneous superselective adrenal arterial embolization (SAAE) with ethanol reduces blood pressure in patients with primary aldosteronism. This study aimed to compare the efficacy of SAAE with mineralocorticoid receptor antagonists (MRA) in treating patients with idiopathic hyperaldosteronism. In this prospective, randomized, controlled trial, we randomly assigned patients with idiopathic hyperaldosteronism in a 1:1 ratio to undergo SAAE (n = 29) or receive MRA (n = 30) treatment. The primary endpoint was the change in mean 24-hour ambulatory systolic blood pressure at 6 months. The secondary endpoints included changes in office blood pressure, home blood pressure, correction of aldosterone-to-renin ratio, and adverse events at 6 months. The mean change in 24-h ambulatory systolic blood pressure from baseline to 6-month follow-up was significantly different between the two groups (-8.4 mmHg; 95% confidence interval, -15.2 to -2.1 mmHg; P < 0.01). Office, home, and ambulatory blood pressure reduction at 6 months was more pronounced in the SAAE group than the MRA group (all P < 0.05). Aldosterone-to-renin ratio was lower in the SAAE group than the MRA group at 1 and 3 months (both P < 0.01), while it had no difference between the two groups at 6 months. None of the patients experienced serious adverse events in the perioperative and 6-month follow-up periods. SAAE, as a hormonal debulking procedure, is superior to MRA in blood pressure control and correction of biochemical abnormalities in patients with idiopathic hyperaldosteronism.

Transmembrane protein 117 knockdown protects against angiotensin-II-induced cardiac hypertrophy.

Mitochondrial dysfunction plays a critical role in the pathogenesis of pathological cardiac hypertrophy. Transmembrane protein 117 modulate mitochondrial membrane potential that may be involved in the regulation of oxidative stress and mitochondrial function. However, its role in the development of angiotensin II (Ang-II)-induced cardiac hypertrophy is unclear. Cardiac-specific TMEM117-knockout and control mice were subjected to cardiac hypertrophy induced by Ang-II infusion. Small-interfering RNAs against TMEM117 or adenovirus-based plasmids encoding TMEM117 were delivered into left ventricles of mice or incubated with neonatal murine ventricular myocytes (NMVMs) before Ang-II stimulation. We found that TMEM117 was upregulated in hypertrophic hearts and cardiomyocytes and TMEM117 deficiency attenuated Ang-II-induced cardiac hypertrophy in vivo. Consistently, the in vitro data demonstrated that Ang-II-induced cardiomyocyte hypertrophy significantly alleviated by TMEM117 knockdown. Conversely, overexpression of TMEM117 exacerbated cardiac hypertrophy and dysfunction. An Ang II-induced increase in cardiac (cardiomyocyte) oxidative stress was alleviated by cardiac-specific knockout (knockdown) of TMEM117 and was worsened by TMEM117 supplementation (overexpression). In addition, TMEM117 knockout decreased endoplasmic reticulum stress induced by Ang-II, which was reversed by TMEM117 supplementation. Furthermore, TMEM117 deficiency mitigated mitochondrial injury in hypertrophic hearts and cardiomyocyte, which was abolished by TMEM117 supplementation (overexpression). Taken together, these findings suggest that upregulation of TMEM117 contributes to the development of cardiac hypertrophy and the downregulation of TMEM117 may be a new therapeutic strategy for the prevention and treatment of cardiac hypertrophy.

Case report: Percutaneous adrenal arterial embolization cures resistant hypertension.

Background: Primary aldosteronism is a common cause of resistant hypertension. Patients with primary aldosteronism due to aldosterone-producing adenoma are generally treated with unilateral adrenalectomy or medical therapy. Superselective adrenal arterial embolization is an alternative treatment for patients with unilateral primary aldosteronism. Case summary: We present a 39-year-old male patient with a 5-year history of primary aldosteronism and secondary hypertension. The patient refused adrenalectomy while accepted pharmacotherapy. Despite taking adequate dose of spironolactone, the patient experienced repeatedly muscle weakness due to hypokalemia and had poor blood pressure control with left ventricular hypertrophy and renal dysfunction. Aldosterone-producing adenoma in the left adrenal gland was confirmed by computerized tomography and adrenal venous sampling. The left middle adrenal artery, which was confirmed to provide the main arterial supply to the aldosterone-producing adenoma, was embolized by injecting 2 ml ethanol. The embolization normalized his blood pressure for up to 3 months and reversed left ventricular hypertrophy. Conclusion: Superselective adrenal arterial embolization could be an alternative treatment for patients with aldosterone-producing adenoma who refuse adrenalectomy.

Capsaicin Prevents Contrast-Associated Acute Kidney Injury through Activation of Nrf2 in Mice.

Capsaicin, a transient receptor potential vanilloid 1 channel agonist, possesses antioxidative properties through activating nuclear factor-erythroid 2-related factor 2 (Nrf2). As oxidative stress is a major contributor to the development of contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of capsaicin against CA-AKI via Nrf2. C57BL/6J mice were treated with dehydration and iodixanol to establish the model of CA-AKI. For pretreatment, capsaicin (0.3 mg/kg) was given via intraperitoneal injection one hour before iodixanol injection. Nrf2-specific siRNA was given through the tail vein to knock down Nrf2. The CA-AKI mouse model had remarkable mitochondrial fragmentation and dysfunction and apoptosis of tubular cells, overproduction of superoxide in renal tubules, increased renal malondialdehyde, tubular epithelial cell injury, and renal dysfunction. Importantly, pretreatment with capsaicin significantly ameliorated tubular cell injury and renal dysfunction with decreased superoxide, renal malondialdehyde, and apoptotic tubular cells and improved mitochondrial morphology and function in the CA-AKI mouse model. The expression of Nrf2 was increased in the kidney from the CA-AKI mouse model and was further enhanced by capsaicin. Administration of siRNA through the tail vein successfully decreased Nrf2 expression in the kidney, and knockdown of Nrf2 by siRNA abolished the beneficial effects of capsaicin on CA-AKI. The present study demonstrated a protective effect of capsaicin pretreatment against CA-AKI via Nrf2.

Adrenal Ablation Versus Mineralocorticoid Receptor Antagonism for the Treatment of Primary Aldosteronism: A Single-Center Prospective Cohort Study.

BACKGROUND: Superselective adrenal arterial embolization (SAAE) is an alternative treatment for patients with primary aldosteronism (PA). This single-center prospective cohort study aimed to compare the efficacy of SAAE with mineralocorticoid receptor antagonists (MRA) in treating patients with PA who refused unilateral adrenalectomy. METHODS: Of the 140 PA patients who were enrolled in the study and completed 12-month follow-up, 74 patients underwent SAAE and 66 received MRA treatment. The clinical and biochemical outcome was compared at 1, 6, and 12 months after the procedure. RESULTS: Baseline clinical and biochemical characteristics of the patients were similar between groups. Office, home, and ambulatory blood pressure reduction at 1 month after discharge was more pronounced in the SAAE group than MRA group (all P < 0.05) while the blood pressure reduction was comparable between the 2 groups at 6 and 12 months. Patients who underwent SAAE took less antihypertensive medications than the MRA group during 12-month follow-up (P < 0.01). Both SAAE and MRA treatment improved renin suppression, aldosterone-to-renin ratio elevation, and hypokalemia at 6 and 12 months, whereas only SAAE but not MRA reduced plasma aldosterone levels. Moreover, SAAE achieved higher rates of complete clinical and biochemical success than MRA (both P < 0.01). Logistic regression found that complete clinical and biochemical success was only directly associated with diagnosis of unilateral PA in contrast to bilateral PA (P < 0.01). CONCLUSIONS: The present study provides evidence that SAAE is a reasonable choice of treatment in patients with either unilateral or bilateral PA in terms of clinical and biochemical outcomes. This study was registered at Chictr.org.cn (ChiCTR2100045896).