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Brain and hypertension: from sympathetic outflow to brain-focused blood pressure management

Hypertension Research volume 49, pages 749–755 (2026)Cite this article

Abstract

Hypertension is both a driver and a consequence of brain dysfunction. The brain regulates circulation via control of autonomic nervous system tone by integrating neural and humoral signals. It is also a vulnerable target of blood pressure (BP)–related injury, ranging from overt stroke to covert small-vessel disease. Recognizing this bidirectional relationship is essential for advancing precision in prevention and treatment. On the mechanistic side, recent work has clarified how the brain renin–angiotensin system, sodium–glucose cotransporter 2, the melanocortin system, and the gut–brain axis shape autonomic output. In addition, renewed attention has been given to centrally acting sympatholytics, imidazoline receptor agonists, which demonstrate antihypertensive efficacy and metabolic neutrality in contemporary trials. Collectively, these studies reinforce that central pathways remain viable therapeutic targets for modulating sympathetic activity. Clinically, multiple investigations highlight that cerebrovascular outcomes depend not only on mean BP but also on patterns and cumulative injury. Total small-vessel disease burden integrates lifetime vascular damage and predicts prognosis after stroke. Nocturnal BP surges and visit-to-visit variability further stratify cerebrovascular risk, while beat-to-beat fluctuations after reperfusion influence recovery. Pulse pressure after intracerebral hemorrhage links systemic hemodynamics with renal and neurological outcomes, and prevention gaps such as untreated hypertension remain striking, especially in younger patients. Together, these advances emphasize that brain health and BP regulation are inseparable. This review highlights recent advances in both central mechanisms of sympathoexcitation and clinical perspectives on cerebrovascular outcomes in hypertension.

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Acknowledgements

We appreciate the editors of Hypertension Research for giving us the opportunity to contribute to this mini-review article.

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Author notes

  1. These authors contributed equally: Shota Ikeda, Keisuke Shinohara.

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shota Ikeda & Keisuke Shinohara

  2. Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA

    Shota Ikeda

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  1. Shota Ikeda
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  2. Keisuke Shinohara
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Correspondence to Shota Ikeda or Keisuke Shinohara.

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Ikeda, S., Shinohara, K. Brain and hypertension: from sympathetic outflow to brain-focused blood pressure management. Hypertens Res 49, 749–755 (2026). https://doi.org/10.1038/s41440-026-02548-1

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