Hypertension
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Experimental studies implicate late systolic load as a determinant of impaired left-ventricular relaxation. We aimed to assess the relationship between the myocardial loading sequence and left-ventricular contraction and relaxation. Time-resolved central pressure and time-resolved left-ventricular geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1214 middle-aged adults without manifest cardiovascular disease from the general population. ⋯ The loading sequence remained independently associated with early diastolic mitral annular velocity after adjustment for systolic mitral annular velocity or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of left-ventricular systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation.
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Heart failure, caused by dilated cardiomyopathy and other cardiac disorders such as hypertension, is a major public health problem with high morbidity and mortality. Corin, a cardiac enzyme that cleaves natriuretic peptides, is a promising biomarker of cardiomyopathy and heart failure, but its functional role in these processes is not understood. We evaluated the potential effects of corin in mice with a well-characterized model of dilated cardiomyopathy. ⋯ Corin overexpression also enhanced heart contractile function (fractional shortening and ejection fraction; P<0.01) and it significantly reduced heart failure as assessed by lung water (P<0.05) and alveolar congestion (P<0.001). Consistent with these observations, corin overexpression significantly prolonged life in mice with dilated cardiomyopathy (P<0.0001). These results provide the first experimental evidence that corin expression plays a role in cardiomyopathy by modulating myocardial fibrosis, cardiac function, heart failure, and survival.
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We previously showed that in hypertensive patients the amount of fluid displaced from the legs overnight is directly related to the severity of obstructive sleep apnea and that the rostral fluid shift was greater in drug-resistant hypertensive patients. The findings suggested that this fluid redistribution increases upper airway collapsibility, yet more direct evidence is lacking. The present study examines the effects of graded lower body positive pressure on leg fluid volume, upper airway cross-sectional area, and neck circumference in patients with drug-resistant hypertension (n=25) and controlled hypertension (n=15). ⋯ Displacement of leg fluid volume was significantly greater in patients with drug-resistant hypertension than in controlled hypertension (P<0.0001), and as a consequence, the former experienced greater reductions in mean upper airway cross-sectional area and oropharyngeal junction area (P=0.001 and P<0.0001, respectively). The findings support the concept that in hypertensive subjects, rostral fluid displacement may participate in the pathogenesis of obstructive sleep apnea by narrowing the upper airway and making it more susceptible to collapse during sleep. The exaggerated fluid volume displacement from the legs and upper airway response to lower body positive pressure in patients with drug-resistant hypertension provide additional evidence of an important link between drug-resistant hypertension and obstructive sleep apnea.
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Arterial stiffness is an independent predictor of cardiovascular disease events and mortality, and like blood pressure, may be influenced by dairy food intake. Few studies have investigated the effects of consumption of these foods on prospective measures of arterial stiffness. The present analysis aimed to investigate the prospective relationship between milk, cheese, cream, and butter consumption and aortic pulse wave velocity, augmentation index, systolic and diastolic blood pressure, as well as cross-sectional relationships between these foods and systolic and diastolic blood pressure and metabolic markers using data from the Caerphilly Prospective Study. ⋯ Across increasing groups of milk intake and quartiles of dairy product intake, glucose (P trend=0.032) and triglyceride concentrations (P trend=0.031) were lower, respectively. The present results confirm that consumption of milk predicts prospective blood pressure, whereas dairy product consumption, excluding butter, is not detrimental to arterial stiffness and metabolic markers. Further research is needed to better understand the mechanisms that underpin these relationships.
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Angiotensin (Ang) II induces vascular injury in part by activating innate and adaptive immunity; however, the mechanisms are unclear. We investigated the role of interferon (IFN)-γ and interleukin (IL)-23 signaling. We infused Ang II into IFN-γ receptor (IFN-γR) knockout mice and wild-type controls, as well as into mice treated with neutralizing antibodies against IL-23 receptor and IL-17A. ⋯ Thus, IFN-γ blockade, but not IL-23 receptor antibody treatment, protects from Ang II-induced cardiac damage and electric remodeling. In the kidney, IFN-γ signaling acts in a cell type-specific manner. Glomerular filtration rate is preserved in the absence of the IFN-γR, whereas podocytes may require the IFN-γR in the presence of Ang II for normal integrity and function.