The long-range objective of these studies is to clarify the mechanisms of the responses of cerebral arterioles to changes in intravascular and transmural pressure. The main areas will be explored: The mechanisms of the sustained cerebral arteriolar dilation and associated functional, morphological and metabolic alterations from acute severe arterial hypertension and the mechanisms of the adjustments in cerebral caliber from alterations in blood pressure in the so-called autoregulatory range. We will explore the hypothesis that the cerebral vascular changes from acute severe hypertension are due to the release of oxygen radicals from the vessel wall into the extracellular space. These radicals are generated in the course of increased metabolism of arachidonate by cyclooxygenase. Their production is mediated by the release of VIP and is calcium dependent. The second objective is to explore the mechanism of the adjustments in cerebral arteriolar caliber in response to moderate changes in arterial blood pressure. We will investigate the participation of both myogenic and metabolic mechanisms. The participation of the former will be investigated by bringing about changes in transmural pressure without a primary change in blood flow via alterations in the external pressure applied to the entire body, while the brain is maintained at atmospheric pressure. The response of cerebral arterioles to metabolic mechanisms will be investigated by bringing about changes in blood flow without alterations in transmural pressure via changes in blood viscosity induced by administration of hypertonic solutions. These solutions cause biphasic changes, initially a decrease in viscosity and hyperemia, and subsequently an increase in viscosity and reduction in blood flow. Further, the mediation of metabolic changes via adenosine will be explored.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Method to Extend Research in Time (MERIT) Award (R37)
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Cardiovascular and Pulmonary Research B Study Section (CVB)
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Virginia Commonwealth University
Schools of Medicine
United States
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Wei, E P; Kontos, H A; Beckman, J S (1996) Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite. Am J Physiol 271:H1262-6
Kontos, H A; Wei, E P (1996) Arginine analogues inhibit responses mediated by ATP-sensitive K+ channels. Am J Physiol 271:H1498-506
Kontos, H A; Wei, E P (1993) Hydroxyl radical-dependent inactivation of guanylate cyclase in cerebral arterioles by methylene blue and by LY83583. Stroke 24:427-34
Kontos, H A (1993) Nitric oxide and nitrosothiols in cerebrovascular and neuronal regulation. Stroke 24:I155-8
Kukreja, R C; Wei, E P; Kontos, H A et al. (1993) Nitric oxide and S-nitroso-L-cysteine as endothelium-derived relaxing factors from acetylcholine in cerebral vessels in cats. Stroke 24:2010-4;discussion 2014-5
Wei, E P; Randad, R S; Levasseur, J E et al. (1993) Effect of local change in O2 saturation of hemoglobin on cerebral vasodilation from hypoxia and hypotension. Am J Physiol 265:H1439-43
Nelson, C W; Wei, E P; Povlishock, J T et al. (1992) Oxygen radicals in cerebral ischemia. Am J Physiol 263:H1356-62
Kontos, C D; Wei, E P; Williams, J I et al. (1992) Cytochemical detection of superoxide in cerebral inflammation and ischemia in vivo. Am J Physiol 263:H1234-42
Wei, E P; Moskowitz, M A; Boccalini, P et al. (1992) Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. Circ Res 70:1313-9
Wei, E P; Kontos, H A (1990) H2O2 and endothelium-dependent cerebral arteriolar dilation. Implications for the identity of endothelium-derived relaxing factor generated by acetylcholine. Hypertension 16:162-9

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