This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. About 20-30% of essential hypertensive patients will have less than the normal (15-20% of awake blood pressure) decline in blood pressure during sleep. This higher than normal sleep blood pressure has been observed during ambulatory blood pressure monitoring and such patients have been termed 'non-dippers' to distinguish them from patients with a normal sleep blood pressure decline, 'dippers'. Patients with nondipping sleep blood pressure are continuously exposed to higher blood pressure levels. This persistent hypertension is likely to be injurious to the endothelium and other organs susceptible to the ill effects of hypertension. Indeed, preliminary studies indicate that nondipper hypertensives have more evidence of hypertensive organ damage. The present study will therefore examine some important issues regarding the criteria for dipper and nondipper categories of blood pressure, the reproducibility of such categorization and the effects of daytime and sleep activity on the decline of blood pressure during sleep. The study will also compare sympathetic nervous system activity, salt sensitivity, and insulin resistance measures in relation to the extent of sleep blood pressure reduction. Finally, endothelial function, retinal vascular structure and left ventricular mass will be compared in dippers and non-dippers. The project will recruit 150 newly diagnosed and untreated hypertensive subjects to eliminate the effects of drug treatment on blood pressure profiles. After an initial 2-week period when the presence of hypertension will be confirmed by clinic blood pressure readings, patients will undergo 2 separate 24-hour ambulatory blood pressure and electronic activity monitoring sessions about 1-2 weeks apart. During these two periods, awake and sleep sympathetic nervous system activity will be evaluated using plasma and urinary catecholamines. Sleep quality will be measured using a questionnaire and actigraphy derived indices of sleep quality. During the next two weeks and while remaining untreated, all patients will undergo endothelial function studies (B-mode ultrasound), retinal vascular structure assessment (high-resolution retinal photography), and left ventricular mass estimation (echocardiography). In the latter two years of the project, salt sensitivity and its relation to dipper and nondipper blood pressure profiles will be studied. The reproducibility of the dipper and nondipper categorization will be examined in relation to the effects of sleep and daytime activity, sleep quality, and sympathetic nervous system activity. Direct comparisons between dipper and nondipper groups will be made in salt sensitivity, insulin resistance, and sympathetic nervous system activity. This study will provide information that will be important if clinical trials targeting nocturnal blood pressure are to be designed.
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