The vascular endothelium is continually exposed to shear stresses associated with blood flow. Changes in hemodynamic shear stress can alter the release of diffusible vasoactive factors from the endothelium, and can therefore alter vascular tone. At the microvascular level, this influence may constitute an important mechanism for the local control of arteriolar resistance and blood flow. The long-term objectives of this study are two fold: (1) to more precisely define the shear-dependent role of the microvascular endothelium in matching blood flow to tissue metabolic demands, and (2) to begin to elucidate the transduction pathways in microvascular endothelial cells through which changes in shear stress are converted into an altered release of vasoactive factors. All experiments will be carried out in the intact micovascular network of the superfused rat spinotrapezius muscle. The first part of this study will combine in-vivo microscopy with various micropipette-based techniques to test the hypothesis that a diffusible factor(s) released from the venular endothelium in response to elevated shear stress contributes to arteriolar dilation and hyperemia during muscle contraction. The capacity for shear-dependent communication between closely-paired venules and arterioles will first be evaluated in resting muscle by observing arteriolar responses to flow-related increases in venular wall shear stress before and after functional impairment of the venular endothelium. The relative contribution of the venular vs. arteriolar endothelium to the changes in arteriolar diameter, blood flow and tissue PO that accompany muscle contraction will be assessed by measuring these responses before and after widespread functional impairment of the venular or arteriolar network endothelium. The second part of this study will use similar in-vivo techniques to identify some of the cellular biochemical processes that are involved in shear stress transduction by the arteriolar endothelium. In these experiments, the magnitude of flow-dependent arteriolar dilation will be examined before and during arteriolar perfusion with various pharmacological inhibitors to test the hypothesized role of G-proteins, membrane potassium channels and the phospholipase-C/inositol triphosphate pathway in arteriolar shear transduction.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Cardiovascular and Renal Study Section (CVB)
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West Virginia University
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Boegehold, Matthew A (2013) The effect of high salt intake on endothelial function: reduced vascular nitric oxide in the absence of hypertension. J Vasc Res 50:458-67
Boegehold, Matthew A (2002) Microvascular structure and function in salt-sensitive hypertension. Microcirculation 9:225-41
Lenda, Deborah M; Boegehold, Matthew A (2002) Effect of a high-salt diet on oxidant enzyme activity in skeletal muscle microcirculation. Am J Physiol Heart Circ Physiol 282:H395-402
Sauls, B A; Boegehold, M A (2001) Reduced PO(2) and adenosine formation preserve arteriolar nitric oxide synthesis during sympathetic constriction in the rat intestine. J Vasc Res 38:104-12
Sauls, B A; Boegehold, M A (2000) Arteriolar wall PO(2) and nitric oxide release during sympathetic vasoconstriction in the rat intestine. Am J Physiol Heart Circ Physiol 279:H484-91
Nurkiewicz, T R; Boegehold, M A (2000) Reinforcement of arteriolar myogenic activity by endogenous ANG II: susceptibility to dietary salt. Am J Physiol Heart Circ Physiol 279:H269-78
Lenda, D M; Sauls, B A; Boegehold, M A (2000) Reactive oxygen species may contribute to reduced endothelium-dependent dilation in rats fed high salt. Am J Physiol Heart Circ Physiol 279:H7-H14
Nurkiewicz, T R; Boegehold, M A (1999) Limitation of arteriolar myogenic activity by local nitric oxide: segment-specific effect of dietary salt. Am J Physiol 277:H1946-55
Linderman, J R; Boegehold, M A (1999) Growth-related changes in the influence of nitric oxide on arteriolar tone. Am J Physiol 277:H1570-8
Nase, G P; Boegehold, M A (1998) Postjunctional alpha 2-adrenoceptors are not present in proximal arterioles of rat intestine. Am J Physiol 274:H202-8

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