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

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 MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors.

Figures

Figure 1. Summary data of beat-by-beat percentage changes in forearm vascular conductance following all muscle sympathetic nerve activity bursts (filled circles), non-bursts (filled triangles) and white noise (open squares)

Brackets denote significant difference from percentage changes in white noise. Values are means ±s.e.

Figure 2. Summary data of beat-by-beat percentage changes in forearm vascular conductance (FVC) following variations in spontaneous muscle sympathetic nerve activity (MSNA) burst pattern and size

A, changes in FVC following consecutive MSNA bursts of increasing length (singlet, couplet, triplet and quadruplet). B, changes in FVC following MSNA bursts divided into quartiles of increasing size (Q1–Q4, respectively). White noise changes are provided for reference (open squares). Brackets denote significant difference from percentage changes in white noise. Values are means ±s.e.

Figure 3. Group data showing forearm vascular conductance nadir responses following variations in spontaneous MSNA burst pattern (left side; grey bars) and size (right side; white bars)

*P < 0.05 vs. singlet patterns or Q1 bursts, respectively. Values are means ±s.e. MSNA, muscle sympathetic nerve activity.

Figure 4. Summary data of beat-by-beat percentage changes in MAP (filled circles), cardiac output (open circles) and total vascular conductance (filled triangles) following spontaneous muscle sympathetic nerve activity bursts

Brackets denote significant difference from percentage changes in each variable's respective white noise (not shown). Values are means ±s.e. CO, cardiac output; MAP, mean arterial pressure; TVC, total vascular conductance.

Figure 5. Summary data of beat-by-beat percentage changes in forearm vascular conductance following all spontaneous muscle sympathetic nerve activity bursts, non-bursts and white noise during saline infusion (A), and during phentolamine+angiotensin II co-infusion (α-adrenergic blockade; B)

Brackets denote significant differences from percentage changes in white noise. Values are means ±s.e.

Figure 6. Group data during forearm infusions showing forearm vascular conductance peak and nadir responses following variations in burst pattern (left side, grey bars) and size (right side, white bars)

Saline infusion responses are shown as solid bars, and phentolamine+angiotensin II co-infusion responses are shown with hatched bars. *P < 0.05 vs. saline, †P < 0.05 vs. singlet patterns. Values are means ±s.e. MSNA, muscle sympathetic nerve activity.

Figure 7. Group data during forearm infusions showing the regression between MSNA burst clusters and nadir percentage changes in forearm vascular conductance

Filled circles show forearm vascular conductance responses during saline infusion, and open circles show responses during phentolamine+angiotensin II co-infusion (α-adrenergic blockade). Correlations displayed are derived from group means. Values are means ±s.e. MSNA, muscle sympathetic nerve activity.