Mitochondrial Dysfunction and the Feedback Loop of Hypertension Mitochondrial dysfunction lies at the root of a self-reinforcing feedback loop that drives the pathology of hypertension Standard treatment by pharma: Drugs like telmisartan Angiotensin II receptor blocker (ARB) address one branch of the problem. True root cause: The cycle begins in the mitochondria. In healthy neurons, the electron transport chain (ETC) naturally leaks a small amount of reactive oxygen species (ROS). Under normal conditions, this is controlled by antioxidants such as mitochondrial superoxide dismutase (MnSOD). When mitochondria become dysfunctional: - Excess ROS: Electron leakage increases beyond antioxidant capacity. - Sympathetic overdrive: ROS amplifies sympathetic nervous system activity, feeding into elevated blood pressure. - Renin–angiotensin activation: Sympathetic overdrive raises Angiotensin II expression. - Kidney damage: Persistent high blood pressure strains the kidneys, which have limited ability to repair themselves. - Vicious cycle: Kidney injury and ongoing oxidative stress further destabilize blood pressure regulation. This creates a cascading forest fire Faulty ETC → oxidative stress in neurons and blood vessels Sympathetic overactivation → chronic Ang II signaling Kidney injury → loss of pressure regulation Systemic damage → sustained hypertension Elevated cortisol and catecholamines perpetuate the loop Notably, the sympathetic nervous system is activated in ~50% of patients with hypertension, highlighting its central role in this self-perpetuating cycle.
