The effect of dietary quercetin on functional and molecular indices of cardiovascular function

Cardiac hypertrophy occurs to normalize ventricular wall stress in response to chronic hypertension. Over time, this process can contribute to heart failure. Evidence indicates that the dietary antioxidant quercetin (Q) lessens hypertension and attenuates cardiac hypertrophy. Our overall hypothesis is that Q exerts these beneficial effects via regulating hypertrophic signal transduction pathways.; Investigation #1. Hypertension and cardiac hypertrophy were produced in rats by 14 days of abdominal aortic constriction (AAC). We hypothesized that hypertension, activation of protein kinase C (PKC) betaII, and cardiac hypertrophy are attenuated in animals that consume Q during this process (AACQ). AAC-evoked hypertension and myocardial growth were attenuated (p < 0.05), and cardiac PKC betaII translocation was abolished (p < 0.05), in AACQ rats.; Investigation #2. We hypothesized that AAC-evoked hypertension, cardiac hypertrophy, activation of Akt and ERK 1/2, indices of lipid and protein oxidation, and arterial dysfunction, are attenuated in AACQ animals. AAC-evoked cardiac hypertrophy and hypertension were less severe (p < 0.05) in AACQ rats. Further, activation of Akt and ERK 1/2 and indices of whole-body oxidant load were blunted (p < 0.05) in AACQ versus AAC animals. These beneficial structural and hemodynamic alterations were not accompanied by deleterious changes to myocardial function.; Investigation #3. We sought to determine whether Q is card ioprotective in a more severe model of hypertension, the spontaneously hypertensive rat (SHR). SHRs consumed standard or Q-supplemented chow (SHRQ) for 10 weeks. Blood pressure was measured weekly, while other variables were assessed at 10 weeks. Arterial pressure was less (p < 0.05) in SHRQ versus SHR rats at 5 weeks. At 10 weeks, arterial pressure, cardiac hypertrophy, myocardial and arterial function, and indices of oxidant load were similar between SHR and SHRQ animals. In contrast, SHR-induced translocation of phosphorylated PKC delta/theta was blunted in SHRQ animals.; We are the first to demonstrate that Q blunts activation of hypertrophic signaling kinases in vivo. Our data indicate that Q lessens hypertension and cardiac hypertrophy in response to AAC, and delays hypertension in SHRs. Discrepancies concerning the efficacy of Q likely are due to the greater severity and duration of hypertension in the SHR versus AAC model.