A number of investigations have demonstrated that arterial baroreflex (CBR) control of blood pressure has a primary role in providing the necessary regulation of the sympathetic neural outflow to active and inactive tissue beds associated with dynamic exercise. In addition, we have documented a reduced vasoconstrictive response to hypotension of the highly trained endurance athlete despite an augmented CBR mediated increase in MSNA. A growing body of evidence suggests that the regulatory role of sympathetic neural outflow to the vasculature is modulated by metabolic by-products released within the active tissue and involve mechanisms of functional sympatholysis. A suggested mechanism of functional sympatholysis is that contraction induced metabolites within the active muscle open ATP-sensitive potassium (KATP) channels and thereby partially inhibit sympathetic vasoconstriction. However, it has recently been demonstrated that the CBR mediated vasoconstriction within the active muscle provides the greatest reflex vasoconstrictor response to hypotension during exercise. Therefore, we hypothesize that the CBR has a fundamental role in the control of MSNA and skeletal muscle vasculature at rest and during exercise. Furthermore, we contend that the CBR regulation of vasomotor function in exercising muscle is altered by local metabolic by-products and their interaction with other vasoactive substances and the KATP channels of the vascular smooth muscle within the active tissue. In addition, these mechanisms of CBR control of the vasculature are modulated by endurance exercise training. To address these hypotheses: Comparisons of carotid baroreflex function curves of blood pressure (BP), MSNA and leg vascular conductance (LVC) will be made between rest, the non-exercising leg (NEL) and the exercising leg (EL) using the classic one-legged exercise protocol performed by humans. Carotid baroreflex function will be assessed using our well established modeling technique. Comparisons of CBR function curves of BP, MSNA and LVC will be made at rest, in the NEL and the EL (except MSNA) between average fit, high fit endurance trained athletes and NIDDM patients treated with glibenclamide and NIDDM patients treated with Metformin. We anticipate that the findings obtained from this project will provide a comprehensive understanding of the fundamental mechanisms involved in the regulation of arterial blood pressure by the arterial baroreflex and its influence on the regulation of vasomotion in active muscle tissue and inactive muscular tissue in matching blood flow to oxygen demand during exercise in humans. These findings will have implications for the care of patients suffering from non-insulin dependent diabetes mellitus (NIDDM), hypertension and cardiac failure.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Respiratory Physiology Study Section (RESP)
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Velletri, Paul A
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University of North Texas
Schools of Medicine
Fort Worth
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Raven, Peter Bernard (2018) Antihypertensive Treatment Fails to Control Blood Pressure During Exercise. Hypertension 72:63-64
White, Daniel W; Shoemaker, J Kevin; Raven, Peter B (2015) Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans. Auton Neurosci 193:12-21
Raven, Peter B; Chapleau, Mark W (2014) Blood pressure regulation XI: overview and future research directions. Eur J Appl Physiol 114:579-86
White, Daniel W; Raven, Peter B (2014) Autonomic neural control of heart rate during dynamic exercise: revisited. J Physiol 592:2491-500
Sugawara, Jun; Brothers, R Matthew; Raven, Peter B et al. (2013) Effect of systemic ?1-adrenergic receptor blockade on central blood pressure response during exercise. J Physiol Sci 63:389-93
Ogoh, Shigehiko; Brothers, R Matthew; Jeschke, Monica et al. (2010) Estimation of cerebral vascular tone during exercise; evaluation by critical closing pressure in humans. Exp Physiol 95:678-85
Wray, D Walter; Raven, Peter B; Sander, Mikael (2008) Diminished baroreflex-induced vasoconstriction following alpha-2 adrenergic receptor blockade in humans. Auton Neurosci 138:114-7
Ogoh, Shigehiko (2008) Autonomic control of cerebral circulation: exercise. Med Sci Sports Exerc 40:2046-54
Raven, Peter B (2008) Recent advances in baroreflex control of blood pressure during exercise in humans: an overview. Med Sci Sports Exerc 40:2033-6
Ogoh, Shigehiko; Brothers, R Matthew; Eubank, Wendy L et al. (2008) Autonomic neural control of the cerebral vasculature: acute hypotension. Stroke 39:1979-87

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