NOS3 and Hypertension: The two-hit HFpEF mouse model of combined HFD with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) administration to inhibit the endothelial nitric oxide synthase (eNOS), established by Schiattarella and colleagues25, unites the two major HFpEF risk factors - hypertension and metabolic syndrome.