Background-Cardiac responses to ␤-adrenergic receptor stimulation are depressed with pressure overload-induced cardiac hypertrophy. We investigated whether exercise training could modify ␤-adrenergic receptor responsiveness in a model of spontaneous hypertension by modifying the ␤-adrenergic receptor desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca 2ϩ cycling proteins. Ϫ7 mol/L) and pacing stress (8.5 Hz). The peak LV developed pressure/ISO dose response was shifted rightward 100-fold in SHR relative to WKY. The peak ISO LV developed pressure response was similar between WKY and SHR-SED and increased in SHR-TRD (PϽ0.05). SHR-TRD showed the greatest lusitropic response to ISO (PϽ0.05) and offset the pacing-induced increase in LV end-diastolic pressure and the time constant of isovolumic relaxation () observed in WKY and SHR-SED. Improved cardiac responses to ISO in SHR-TRD were associated with normalized myocardial levels of GRK2 (PϽ0.05). SHR displayed increased L-type Ca 2ϩ channel and sodium calcium exchanger abundance compared with WKY (PϽ0.001). Training increased ryanodine receptor phosphorylation and phospholamban phosphorylation at both the Ser 16 and Thr 17 residues (PϽ0.05). Conclusions-Exercise training in hypertension improves the inotropic and lusitropic responsiveness to ␤-adrenergic receptor stimulation despite augmenting LV wall thickness. A lower GRK2 abundance and an increased phosphorylation of key Ca 2ϩ cycling proteins may be responsible for the above putative effects. (Circulation. 2005;111:3420-3428.)

BACKGROUND Visit-to-visit clinic blood pressure variability (BPV) and 24-hour BPV have both been identified as independent risk factors for cardiovascular (CV) morbidity and mortality; however the mechanisms contributing to the increased CV risk as yet are unclear. The purpose of this study was to assess the relationship between BPV and endothelial function in a cohort of putatively healthy African Americans. METHODS 36 African Americans who were sedentary, non-diabetic, non-smoking, free of cardiovascular and renal disease and not on antihypertensive medication followed an American Heart Association low fat, low salt diet for 6 weeks. Upon completion of the 6-week dietary stabilization period, participants underwent 24-hour ambulatory BP monitoring and had their office BP measured on three separate days. Right brachial artery diameter was assessed at rest, during reactive hyperemia (flow-mediated dilation: FMD), and after nitroglycerin administration (nitroglycerin-mediated dilation: NMD). RESULTS Participants classified as having decreased endothelial function according to either %FMD or the FMD/NMD ratio had significantly higher 24-hour BPV and a trend for higher visit-to-visit BPV when compared to participants with normal endothelial function. Continuous variable analyses revealed a significant positive association between NMD and 24-hour diastolic BPV (DBPV). Visit-to-visit systolic BPV (SBPV), 24-hour SBPV, and 24-hour DBPV were all negatively associated with the FMD/NMD ratio. All relationships remained significant after adjustment for age, BMI, and mean BP levels. CONCLUSIONS These results may suggest that BPV is in increased in African Americans with decreased endothelial function and is associated with the vascular smooth muscle response to nitric oxide.

Recent attempts at rebuilding the myocardium using stem cells have yielded disappointing results. The lack of a supporting vasculature may, in part, explain these disappointing findings. However, concerns over possible side effects have hampered attempts at revascularizing the infarcted myocardium using systemic delivery of proangiogenic compounds. In this study, we develop the technology to enhance the morphology and function of postinfarct neovasculature. Previously, we have shown that the up-regulated expression of endothelial cell adhesion molecules in the myocardial infarction (MI) region provides a potential avenue for selectively targeting drugs to infarcted tissue. After treatment with anti-P-selectin-conjugated liposomes containing vascular endothelial growth factor (VEGF), changes in cardiac function and vasculature post-MI were quantified in a rat MI model. Targeted delivery of VEGF to post-MI tissue resulted in significant increase in fractional shortening and improved systolic function. These functional improvements were accompanied by a 21% increase in the number of anatomical vessels and a 74% increase in the number of perfused vessels in the MI region of treated animals. No significant improvements in cardiac function were observed in untreated, systemic VEGF-treated, nontargeted liposome-treated, or blank immunoliposome-treated animals. Targeted delivery of low doses of proangiogenic compounds to post-MI tissue results in significant improvements in cardiac function and vascular structure.

A lthough the overall rate of death associated with cardiovascular disease (CVD) continues to decline in the United States, [1][2][3] CVD is a leading cause of mortality and disability. The burden of CVD remains high, underscoring the need to improve long-term management of CVD as a chronic illness. Effective implementation of current treatment guidelines for primary and secondary prevention of CVD relies heavily on patient knowledge and engagement in carrying out the plan of care. Healthcare reforms have increasingly shifted the responsibility for self-management to patients and families as hospital stays and ambulatory visits have become shorter and less frequent.Background-The burden of cardiovascular disease as a chronic illness increasingly requires patients to assume more responsibility for their self-management. Patient education is believed to be an essential component of cardiovascular care; however, there is limited evidence about specific therapeutic patient education approaches used and the impact on patient self-management outcomes. Methods and Results-An integrative review of the literature was conducted to critically analyze published research studies of therapeutic patient education for self-management in selected cardiovascular conditions. There was variability in methodological approaches across settings and disease conditions. The most effective interventions were tailored to individual patient needs, used multiple components to improve self-management outcomes, and often used multidisciplinary approaches. Conclusions-This synthesis of evidence expands the base of knowledge related to the development of patient selfmanagement skills and provides direction for more rigorous research. Recommendations are provided to guide the implementation of therapeutic patient education in clinical practice and the design of comprehensive self-management interventions to improve outcomes for cardiovascular patients. (Circ Cardiovasc Qual Outcomes. 2017;10:e000025.