Diminished baroreflex-induced vasoconstriction following alpha-2 adrenergic receptor blockade in humans

Abstract

The relative contribution of alpha adrenergic receptor subtypes in the transduction of sympathetic nerve activity (SNA) during carotid baroreflex (CBR) engagement is not well understood. Therefore, we compared the hemodynamic consequence of CBR-mediated sympatho-excitation via neck pressure (NP) before and after alpha-2 adrenergic blockade with intra-arterial yohimbine. Leg blood flow was measured using 2D and Doppler ultrasound, and arterial blood pressure was determined directly. NP caused the expected vasoconstriction, and this response was significantly reduced (by 50-60%) when NP was repeated after yohimbine. These data indicate that alpha-2 adrenergic receptors contribute significantly to CBR-induced vasoconstriction in the human leg under resting conditions. KeywordsBaroreflex; Yohimbine; Leg Blood Flow; ultrasound Doppler In response to a hypotensive stimulus, the carotid baroreceptors respond with a reflex increase in sympathetic nerve activity (SNA). In the peripheral circulation, this results in vasoconstriction and subsequent decreased systemic vascular conductance via binding of norepinephrine (NE) to both alpha-1 and alpha-2 adrenergic receptors on vascular smooth muscle. However, the relative contribution of adrenergic receptor subtypes in the transduction of SNA during carotid baroreflex (CBR) engagement is not well understood in humans.While the principle action of the CBR is towards arterial blood pressure homeostasis, we have demonstrated that acute CBR-mediated changes in sympathetic outflow and the subsequent impact on systemic vascular conductance also heavily influence beat-to-beat regulation of skeletal muscle blood flow Wray et al., 2004a). From a clinical perspective, CBR sensitivity has been demonstrated to be diminished in heart failure (Eckberg et al., 1971), hypertension (Bristow et al., 1969), and chronic obstructive pulmonary disease (Patakas et al., 1982), conditions also characterized by dysfunction in skeletal muscle perfusion. In this

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“…This is likely mediated by the interaction of NE with hormone sensitive lipase (HSL), the rate limiting enzyme in lipolysis [ 9 ]. Yohimbine may also aid in lipolysis by acting to improve blood flow [ 10 ], and hence, the transport of fatty acids to peripheral tissues to undergo oxidation.…”

The Translational Value of Psychophysiology Methods and Mechanisms: Multilevel, Dynamic, Personalized

“…On average, baroreflex functioning has a robust relationship to physical and mental health (Abboud, 2010;Tracey, 2009) and alcohol and drug use (Bär et al, 2006;Wray et al, 2008). On average, there appear to be immediate as well as chronic clinical benefits of resonance breathing and HRV biofeedback in multiple populations (Eisenberg et al, 2004;Hassett et al, 2007;Karavidas et al, 2007;Lehrer & Va schillo, 2004;Reiner, 2008;Sherlin & Wyckoff, 2008;Siepmann et al, 2008;Sutarto et al, 2012;Zucker et al, 2009).…”