An Animal Model of Coronary Microvascular Dysfunction ( CMD ) in the Female Spontaneously Hypertensive Rat: The Role of Diet

OBJECTIVE: Coronary microvascular dysfunction (CMD) drives angina in patients with ischemia with non-obstructive coronary artery disease, a condition that is more prevalent in females. Effective treatment strategies remain limited, in part, due to the scarcity of physiologically relevant animal models. Indeed, while CMD has been studied in animals with diabetes or fed high-fat diets, hypertension is the predominant risk factor for CMD in humans, but is not captured by these models. METHODS: 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. RESULTS: SHRs on a purified diet, but not WKYs or SHRs consuming GBC, exhibited impaired coronary flow reserve as assessed by echocardiography. This occurred despite the persistence of hypertension in SHRs irrespective of diet. CONCLUSIONS: SHRs develop a diet-dependent CMD, which can serve as a model to study hypertension-related CMD.