SARS-CoV-2 and Hypertension: Evidence Supporting Invasion into the Brain Via Baroreflex Circuitry and the Role of Imbalanced Renin-Angiotensin-Aldosterone-System
This study explores the hypothesis that SARS-CoV-2 infection may contribute to hypertension by affecting the central nervous system, particularly through invasion into the brain via baroreflex circuitry, and by disrupting the balance of the renin-angiotensin-aldosterone system (RAAS).
- Neuroinvasion of SARS-CoV-2: The study discusses the neurotropic and neuroinvasive characteristics of coronaviruses, including SARS-CoV-2, which may invade the central nervous system (CNS) and affect various neural circuits. This invasion can lead to long-lasting viral presence and chronic neurological damage.
- Hypertension as a Critical COVID-19 Risk Factor: Hypertension is identified as a major risk factor for COVID-19 severity. The study indicates a higher prevalence of hypertension among COVID-19 patients and suggests a potential link between SARS-CoV-2 infection and the development or worsening of hypertension.
- Baroreflex Circuitry and Blood Pressure Regulation: SARS-CoV-2 is hypothesized to invade carotid and aortic baroreceptors, leading to infection of key brain areas like the nucleus tractus solitarii (NTS) and the paraventricular hypothalamic nucleus (PVN). This invasion can disrupt blood pressure regulation at a central level, potentially leading to transient or permanent hypertension.
- Imbalance in the RAAS: The study discusses the role of RAAS in blood pressure regulation and how SARS-CoV-2 infection might disrupt its balance. It suggests that the virus’s interaction with ACE2 receptors can lead to an increase in angiotensin II (ANG-II) levels, exacerbating inflammatory responses and contributing to hypertension.
- Effects of ANG-II on CNS and Hypertension: Elevated levels of ANG-II are associated with increased microglial activation, oxidative stress, and inflammation in the CNS. This may lead to altered neurotransmission and increased blood pressure. The study also notes the role of ANG-II in promoting the inflammatory response, which can contribute to vascular inflammation and hypertension.
- Role of ADAM17: The study highlights the role of ADAM17, a metalloprotease, in SARS-CoV-2 pathophysiology. Activation of ADAM17 by ANG-II can lead to increased shedding of ACE2, altering the balance of RAAS. Elevated ADAM17 levels are associated with hypertension, neuroinflammation, and may contribute to the severity of COVID-19 in hypertensive individuals.
- Potential Neurological Sequelae: The study suggests that SARS-CoV-2-induced hypertension could result from damage to specific neural circuits, particularly those involving GABAergic neurotransmission in the PVN and NTS. This damage can be attributed to elevated levels of ROS, oxidative stress, and changes in neurotransmission, indicating a direct involvement of SARS-CoV-2 in hypertensive responses.
In summary, this study provides a comprehensive examination of how SARS-CoV-2 may contribute to hypertension through its effects on the CNS and RAAS. It highlights the complex interplay between viral infection, immune response, and cardiovascular regulation, suggesting new avenues for understanding and potentially treating hypertension in COVID-19 patients.