[Blood pressure variability-induced aggravation of hypertensive organ damages]

Area of Science:

• Cardiovascular Research
• Hypertension Pathophysiology
• Vascular Biology

Context:

• Elevated blood pressure (BP) and increased BP variability are linked to organ damage and adverse cardiovascular events.
• The precise molecular mechanisms underlying BP variability's detrimental effects on organs remain unclear.

Purpose:

• To investigate the molecular mechanisms by which increased BP variability exacerbates organ damage in hypertension.
• To establish a chronic rat model combining hypertension and large BP variability.

Summary:

• A novel rat model with hypertension and large BP variability was developed using bilateral sino-aortic denervation in spontaneously hypertensive rats.
• Large BP variability was found to induce chronic myocardial inflammation via local angiotensin II and mineralocorticoid receptor activation, worsening cardiac hypertrophy, fibrosis, and systolic dysfunction.
• In hypertensive kidneys, large BP variability aggravated arteriolosclerotic changes and ischemic cortical fibrosis through the local angiotensin II system.

Impact:

• Identifies intramyocardial and pre-glomerular arterioles as initial targets of large BP variability, coining the term "strain vessel vasculopathy".
• Provides novel insights into the mechanisms driving hypertensive organ damage, specifically linking BP variability to inflammation and fibrosis.
• Suggests "strain vessel vasculopathy" as a new conceptual framework for understanding and potentially treating BP variability-induced organ damage.