The role of α‐adrenergic receptors in mediating beat‐by‐beat sympathetic vascular transduction in the forearm of resting man

Abstract

Key Points• Sympathetic support of blood pressure demands the efficient control of vascular tone; however, little is known regarding how spontaneously occurring bursts of muscle sympathetic nerve activity (MSNA) dynamically influence forearm vascular conductance.• This study examined the extent to which spontaneous MSNA bursts evoke changes in forearm vascular conductance and blood pressure with and without local α-adrenergic blockade in young healthy men during supine rest.• We observed that under resting conditions, forearm vascular conductance increases briefly and then significantly decreases in association with the total amount of the preceding MSNA; however, during α-adrenergic blockade the decrease in vascular conductance is eliminated.• These results indicate that normal variations in spontaneous MSNA burst activity are systematically followed by transient and robust responses of forearm vasoconstriction and that this influence is mediated via α-adrenergic receptor mechanisms.Abstract Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P = 0.016) and then robustly decreased to a nadir of −5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (-2.1 ± 0.7% and -0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous

Characterizing rapid-onset vasodilation to single muscle contractions in the human leg

“…The ECG and BP signals were sampled at 1 kHz and embedded as data streams into an AVI file containing video images of the femoral and brachial arteries with corresponding blood velocity waveforms outsourced from the ultrasound at a sampling rate of 30 Hz. A custom-designed edge detection and wall tracking software (LabVIEW; National Instruments) was used to determine beat-by-beat arterial diameters and weighted mean blood velocity offline (13,15,16,33). These data were processed using a second custom LabVIEW program, which generated synchronized beat-by-beat data of all recorded variables gated by the R-wave of the ECG.…”

“…All experimental measurements were acquired into a custom Lab-VIEW program interfaced with video output of the Doppler ultrasound machine as previously described in detail by our laboratory (13,15,16,33). The ECG and BP signals were sampled at 1 kHz and embedded as data streams into an AVI file containing video images of the femoral and brachial arteries with corresponding blood velocity waveforms outsourced from the ultrasound at a sampling rate of 30 Hz.…”

“…Femoral and brachial artery diameter and blood velocity profiles were measured continuously using a high-resolution duplex-Doppler ultrasound system (Logiq P5; GE, Milwaukee, WI), as previously described by our laboratory (3,13,15,33). For leg contractions, the common femoral artery of the right leg was scanned longitudinally, distal to the inguinal crease ϳ2-3 cm proximal from the bifurcation of the superficial and deep femoral artery branches.…”

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

“…Resting values for BP, MSNA, and HR were calculated as mean values over a 10-min steady-state period. MSNA was analyzed using a custom LabVIEW program (12,13). MSNA was quantified as burst frequency (bursts/min), burst incidence (bursts/100 cardiac cycles) and total activity (burst frequency multiplied by mean burst amplitude; AU/min).…”

Influence of spontaneously occurring bursts of muscle sympathetic nerve activity on conduit artery diameter

“…Together, these data support the view that conduit arteries are influenced by MSNA, but whether such interpretations can be extrapolated to rest and the naturally occurring oscillations in MSNA is unknown. To our knowledge, the potential beat-by-beat influence of spontaneous MSNA on conduit artery diameter has not been explored.Our laboratory has recently advanced the use of spiketriggered averaging to understand the effects of spontaneously occurring MSNA bursts during rest (7,8,36). Collectively we have determined that MSNA bursts produce robust and dynamic beat-by-beat increases in arterial BP, primarily via decreases in limb vascular conductance through an ␣-adrenergic mechanism.…”