biostudies-literatureMesquita TNHLBI NIH HHS45-60https://www.ebi.ac.uk/biostudies/studies/S-EPMC9083886biostudies-literatureUnknown145(1)<h4>Background</h4>The ability to increase heart rate during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiological heart rate response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown.<h4>Methods</h4>Dahl salt-sensitive rats fed a high-salt diet and C57Bl6 mice fed a high-fat diet and an inhibitor of constitutive nitric oxide synthase (Nω-nitro-L-arginine methyl ester [L-NAME]; 2-hit) were used as models of HFpEF. Myocardial infarction was created to induce HF with reduced ejection fraction. Rats and mice fed with a normal diet or those thatCirculationMechanisms of Sinoatrial Node Dysfunction in Heart Failure With Preserved Ejection Fraction.PMC9083886U01 HL141074R01 HL142496R01 HL126802R01 HL147570R01 HL135866Liang JACingolani EGoldhaber JICho JHMesquita TZhang RLin YNSanchez LYu JKLiu WTrayanova NAfalseMechanisms of Sinoatrial Node Dysfunction in Heart Failure With Preserved Ejection Fraction.<h4>Background</h4>The ability to increase heart rate during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiological heart rate response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown.<h4>Methods</h4>Dahl salt-sensitive rats fed a high-salt diet and C57Bl6 mice fed a high-fat diet and an inhibitor of constitutive nitric oxide synthase (Nω-nitro-L-arginine methyl ester [L-NAME]; 2-hit) were used as models of HFpEF. Myocardial infarction was created to induce HF with reduced ejection fraction. Rats and mice fed with a normal diet or those that2022-01-01T00:00:00Z2022 Jan2026-05-30T15:26:13.648Z2025-04-04T10:01:51.821ZS-EPMC90838863490569610.1161/CIRCULATIONAHA.121.05497610.1161/circulationaha.121.054976