Persistently elevated arterial blood pressure (systolic ≥140 mmHg or diastolic ≥90 mmHg). Represents a failure of normal blood pressure regulation involving the kidneys, vasculature, autonomic nervous system, and neuroendocrine systems (RAAS, sympathetic, AVP).
Multiple interconnected mechanisms: (1) RAAS overactivation (angiotensin II causes vasoconstriction, aldosterone increases sodium retention), (2) sympathetic hyperactivity (norepinephrine increases vascular tone and cardiac output), (3) endothelial dysfunction (reduced NO, increased endothelin), (4) vascular remodeling (increased arterial stiffness), (5) chronic inflammation (IL-6, TNF promote vascular dysfunction), (6) impaired pressure natriuresis (kidney fails to excrete sodium at elevated pressure), (7) insulin resistance (hyperinsulinemia increases SNS activity and sodium retention).
In cPNI framework, hypertension is evolutionary mismatch disease. The RAAS and AVP systems evolved for salt/water conservation in ancestral low-salt environment. Modern high-salt diet, chronic stress, inflammation, and insulin resistance chronically activate these systems. Treatment must address root causes: reduce sodium, manage stress (SNS/RAAS activation), resolve inflammation, improve insulin sensitivity, support endothelial function (NO production).
- Definition: ≥140/90 mmHg persistently
- Primary risk factor for stroke, myocardial infarction, kidney disease
- ~90% is 'essential hypertension' (no single cause identified)
- RAAS activation central: angiotensin II vasoconstriction, aldosterone sodium retention
- Sympathetic overactivity increases vascular resistance
- Endothelial dysfunction reduces NO availability
- Chronic inflammation (IL-6, CRP) predicts hypertension development
- Salt sensitivity varies (genetic and acquired factors)
- Insulin resistance and hyperinsulinemia contribute via SNS activation
- Stress-induced cortisol and catecholamines elevate BP acutely and chronically
- RAAS — Central mechanism; angiotensin II and aldosterone drive hypertension
- angiotensin II — Potent vasoconstrictor increasing peripheral resistance
- aldosterone — Increases sodium retention, expanding blood volume
- renin — Rate-limiting enzyme initiating RAAS cascade
- ACE — Converts angiotensin I to angiotensin II; target of ACE inhibitors
- sympathetic nervous system — Overactivation increases vascular tone and cardiac output
- catecholamines — Norepinephrine and epinephrine acutely and chronically elevate BP
- chronic stress — Drives hypertension via sustained RAAS and SNS activation
- cortisol — Chronic elevation increases vascular reactivity and sodium retention
- endothelial dysfunction — Reduced NO bioavailability impairs vasodilation
- inflammation — IL-6, TNF, CRP promote vascular dysfunction and hypertension
- insulin resistance — Hyperinsulinemia activates SNS and promotes sodium retention
- salt — Excess dietary sodium activates RAAS and volume expansion
- AVP — Vasopressin increases water retention and vascular tone
- oxidative stress — ROS reduce NO bioavailability and damage endothelium
- obesity — Adipose tissue activates RAAS; mechanical and metabolic links to hypertension
- kidney — Impaired pressure natriuresis central to hypertension pathogenesis
- arterial stiffness — Vascular remodeling increases systolic BP
- evolutionary mismatch — RAAS evolved for salt scarcity; maladaptive in modern high-salt environment