Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. Clinical trial registration NCT02918305 (http://www.clinicaltrials.gov).

The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a non-secreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of AT1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin which was dependent upon AT1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventral lateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension.

Aims Cardiac rehabilitation (CR) is an evidence-based, secondary preventive strategy that improves mortality and morbidity rates in patients with heart failure (HF). However, the implementation and continuation of CR remains unsatisfactory, particularly for outpatients with physical frailty. This study investigated the efficacy and safety of a comprehensive home-based cardiac rehabilitation (HBCR) programme that combines patient education, exercise guidance, and nutritional guidance using information and communication technology (ICT). Methods and resultsThis study was a single-centre, open-label, randomized, controlled trial. Between April 2020 and November 2020, 30 outpatients with chronic HF (New York Heart Association II-III) and physical frailty were enrolled. The control group (n = 15) continued with standard care, while the HBCR group (n = 15) also received comprehensive, individualized CR, including ICT-based exercise and nutrition guidance using ICT via a Fitbit® device for 3 months. The CR team communicated with each patient in HBCR group once a week via the application messaging tool and planned the training frequency and intensity of training individually for the next week according to each patient's symptoms and recorded pulse data during exercise. Dietitians conducted a nutritional assessment and then provided individual nutritional advice using the picture-posting function of the application. The primary outcome was the change in the 6 min walking distance (6MWD). The participants' mean age was 63.7 ± 10.1 years, 53% were male, and 87% had non-ischaemic heart disease. The observed change in the 6MWD was significantly greater in the HBCR group (52.1 ± 43.9 m vs. À4.3 ± 38.8 m; P < 0.001) at a 73% of adherence rate. There was no significant change in adverse events in either group. Conclusions Our comprehensive HBCR programme using ICT for HF patients with physical frailty improved exercise tolerance and improved lower extremity muscle strength in our sample, suggesting management with individualized ICT-based programmes as a safe and effective approach. Considering the increasing number of HF patients with frailty worldwide, our approach provides an efficient method to keep patients engaged in physical activity in their daily life.

Exercise training normalizes sympathetic outflow in hypertension and chronic heart failure. The aim of this study was to determine whether the exercise training inhibits sympathetic nerve activity (SNA) via reduction of oxidative stress through blocked angiotensin II type 1 receptor (AT(1)R) in rostral ventrolateral medulla (RVLM). We divided stroke-prone spontaneously hypertensive rats (SHRSP) into SHRSP with exercised training (SHRSP-EX) and control (SHRSP-C). SNA and oxidative stress in the RVLM were significantly lower in SHRSP-EX than in SHRSP-C. These results suggest that exercise training inhibits SNA via reduction of oxidative stress through blocked AT(1)R in the RVLM of hypertension.