A cross-organ, multimodel single-cell atlas of hypertension maps cellular and molecular changes across six organs—hypothalamus, kidney, mesenteric artery, left ventricle, middle cerebral artery, and peripheral blood mononuclear cells—using three animal models to highlight common and model-specific mechanisms of hypertension and end-organ damage.

The study uses three animal models—angiotensin II–treated mice, Dahl salt-sensitive rats, and spontaneously hypertensive rats—to provide a comprehensive cross-organ view of hypertension across six tissues.

A conserved vascular smooth muscle cell gene program linked to blood pressure is identified, alongside cross-segment renal tubular programs tied to renal injury and blood pressure, and tissue-specific endothelial adaptations involving lipid handling, shear stress responses, and cardioprotective signaling.

Integration with human GWAS data reveals both model-specific and shared cell-type–trait associations, indicating that each model captures complementary aspects of human hypertension genetics.

Functional genetic validation prioritizes a noncoding variant (rs28451064) and demonstrates, via genome editing, its in vivo effect on blood pressure and regulation of nearby genes such as SLC5A3 and RCAN1, potentially through chromatin interactions.