The long-term objective of these studies is to clarify the relationship between morphology and function of blood vessels in the brain, and to understand the influence of structural changes produced by chronic hypertension and aging on function of the vessel wall. We propose to use a new method that we developed for analysis of cerebral vascular mechanics in vivo, and a morphometric method to quantitate components of the vessel wall, to examine several concepts that have emerged recently. First, chronic hypertension may alter smooth muscle contraction in blood vessels of the brain. We propose to test the hypothesis that contraction of smooth muscle in cerebral arterioles is augmented in early hypertension, prior to the development of vascular hypertrophy, and contraction may be affected by structural alterations that develop during prolonged hypertension. Furthermore, effects of chronic hypertension on smooth muscle contraction may be different with respect to vessel size and brain region. Second, effects of aging on structure and function of blood vessels in the brain may be similar, in some respects, to effects of chronic hypertension. For example, large arteries in the brain develop thickening of the vessel wall and become less distensible during aging, as well as during chronic hypertension. Although passive characteristics are altered, effects of aging on active characteristics of cerebral vessels in unclear. We propose to test the hypothesis that structural alterations may occur during aging and modulate responses of cerebral vessels to smooth muscle activation. Studies are planned in relation to both of these concepts. First, we propose to test the hypothesis that arterioles account for augmentation of autoregulatory constriction in the brain during chronic hypertension. Specifically, we plan to determine whether 1) maximal active stress of cerebral arterioles is increased in early hypertension, 2) maximal active stress is preserved in established hypertension, and 3) the effect of chronic hypertension on maximal active stress of brain vessels is dependent on vessel size. Studies also are planned to determine whether responses of arterioles to chronic hypertension are heterogeneous with respect to brain region. Second, we propose to examine effects of aging on structure and distensibility of arterioles in the brain. We have designed studies to test the hypothesis that cerebral arterioles develop hypertrophy and become more distensible during aging. Studies also are planned to determine whether effects of aging on structure and distensibility of brain vessels are different in arterioles and large arteries. In addition, we propose to examine effects of aging on morphometry and active mechanics of smooth muscle in arterioles of the brain. We also plan to determine whether maximal active stress of vessels in the brain is preserved in arterioles, but reduced in large arteries. Finally studies are planned to determine whether aging impairs autoregulation of cerebral blood flow. In summary, these studies will use state-of-the-art methods to obtain information that is relevant, not only to effects of chronic hypertension and aging on the cerebral circulation, but also with respect to the interaction of structure and function in arterioles of the brain.
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