# Low and High Pressor Doses of Ang II Lead to Two Distinct Phenotypes of Hypertensive Heart Disease in Mice

## TL;DR

This study shows that different doses of Ang II in mice lead to two distinct types of heart disease, even with similar blood pressure levels.

## Contribution

The study reveals that Ang II induces distinct hypertensive heart disease phenotypes independent of blood pressure regulation.

## Key findings

- Low and high doses of Ang II caused similar hypertension but only high doses led to left ventricular hypertrophy and cardiac dysfunction.
- Both groups showed aortic dilatation and decreased wall strain, but only high-dose Ang II caused significant myocardial remodeling.
- ECG waveform changes were similar in both groups, indicating altered electrical conductivity.

## Abstract

Hypertension is a major contributor to cardiovascular diseases, being the most common comorbidity and the biggest risk factor in heart failure with preserved ejection fraction. Angiotensin II (Ang II) is a known hypertension and heart failure inducer in mice, but its role in the causality in phenotype development remains unclear. Here, hypertension was induced with low (LowA) or high (HighA) pressor doses of Ang II in mice. Both LowA and HighA groups demonstrated equal levels of hypertension with aortic dilatation and decreased aortic wall strain, but only HighA developed left ventricular hypertrophy with advanced cardiac dysfunction, demonstrating the hypertension‐independent effects of Ang II on myocardial remodeling. Alterations in electrical conductivity occurred similarly in both groups, with prominent ECG waveform aberrations. The study demonstrates two distinct hypertensive heart disease phenotypes induced by Ang II, providing a valuable preclinical framework that emphasizes the critical role of Ang II in diastolic dysfunction and vascular remodeling beyond its effects on the regulation of blood pressure.