An animal model of coronary microvascular dysfunction (CMD) in the female spontaneously hypertensive rat: the role of diet

Coronary microvascular dysfunction (CMD) drives angina in patients with ischemia non-obstructive coronary artery disease, a condition that is more prevalent in females. Effective treatment strategies and a detailed mechanistic understanding of CMD remain limited, in part, due to scarcity of physiologically relevant animal models. Indeed, while CMD has been studied in animals with diabetes and/or fed high-fat diets, in fact, hypertension is the predominant risk factor for CMD in humans but is not captured by these models. Thus, we characterized the CMD that arose in female spontaneously hypertensive rats (SHRs). We measured coronary flow reserve, alongside basic cardiovascular function in SHRs and normotensive Wistar Kyoto rats (WKYs) fed a purified diet, as well as SHRs consuming a grain-based chow (GBC) diet. SHRs on a purified diet, but not WKYs or SHRs consuming GBC, exhibited impaired coronary flow reserve as assessed by echocardiography. Thus, SHRs develop a diet-dependent CMD, which can serve as a model to study hypertension-related CMD.