Young, Benjamin E.

Insulin acts centrally to stimulate sympathetic vasoconstrictor outflow to skeletal muscle and peripherally to promote vasodilation. Given these divergent actions, the “net effect” of insulin on the transduction of muscle sympathetic nerve activity (MSNA) into vasoconstriction and thus, blood pressure (BP) remains unclear. We hypothesized that sympathetic transduction to BP would be attenuated during hyperinsulinemia compared with baseline. In 22 young healthy adults, MSNA (microneurography), and beat-to-beat BP (Finometer or arterial catheter) were continuously recorded, and signal-averaging was performed to quantify the mean arterial pressure (MAP) and total vascular conductance (TVC; Modelflow) responses following spontaneous bursts of MSNA at baseline and during a euglycemic-hyperinsulinemic clamp. Hyperinsulinemia significantly increased MSNA burst frequency and mean burst amplitude (baseline: 46 ± 6 au; insulin: 65 ± 16 au, P < 0.001) but did not alter MAP. The peak MAP (baseline: 3.2 ± 1.5 mmHg; insulin: 3.0 ± 1.9 mmHg, P = 0.67) and nadir TVC ( P = 0.45) responses following all MSNA bursts were not different between conditions indicating preserved sympathetic transduction. However, when MSNA bursts were segregated into quartiles based on their amplitudes at baseline and compared with similar amplitude bursts during hyperinsulinemia, the peak MAP and TVC responses were blunted (e.g., largest burst quartile: MAP, baseline: Δ4.4 ± 1.7 mmHg; hyperinsulinemia: Δ3.0 ± 0.8 mmHg, P = 0.02). Notably, ∼15% of bursts during hyperinsulinemia exceeded the size of any burst at baseline, yet the MAP/TVC responses to these larger bursts (MAP, Δ4.9 ± 1.4 mmHg) did not differ from the largest baseline bursts ( P = 0.47). These findings indicate that increases in MSNA burst amplitude contribute to the overall maintenance of sympathetic transduction during hyperinsulinemia.

Insulin plays an important role in post‐prandial blood pressure (BP) regulation. Within the central nervous system insulin acts to stimulate sympathetic outflow to skeletal muscle. Concurrently, insulin acts locally in the periphery to promote vasodilation and is suggested to also attenuate sympathetically‐mediated vasoconstriction. Given these divergent actions, the ‘net effect’ of insulin on the sympathetic control of BP remains incompletely understood. Therefore, the purpose of this study was to examine the effect of hyperinsulinemia on sympathetic transduction to BP. To accomplish this, in 10 young healthy men, heart rate (ECG), BP (finometer or brachial arterial line) and muscle sympathetic nerve activity (MSNA) were measured at rest and during euglycemic‐hyperinsulinemia. Signal‐averaging was used to characterize the changes in mean arterial pressure (MAP) and total vascular conductance (TVC; derived from ModelFlow) over 10 cardiac cycles following spontaneous bursts of MSNA at rest and during hyperinsulinemia. No significant differences were found in the peak MAP (Rest: ∆2.8 ± 0.3; Insulin: ∆2.4 ± 0.2 mmHg, P=0.15) or TVC (Rest: ∆‐3.0 ± 0.4; Insulin: ∆‐2.7 ± 0.5 mL/min/mmHg, P=0.38) responses following bursts of MSNA between rest and hyperinsulinemia (i.e., ‘net’ sympathetic transduction was unchanged). Notably, the average size of normalized MSNA bursts was increased during hyperinsulinemia (Rest: 45.6 ± 1.8; Insulin 65.3 ± 5.0 Au, P<0.01). To take into account changes in burst height, MSNA bursts were divided into amplitude‐matched bins. When MSNA burst amplitude bins were matched between rest and hyperinsulinemia, sympathetic transduction for a given burst amplitude was blunted during insulin infusion (e.g., largest resting bursts: MAP, Rest: ∆4.4 ± 0.5; Insulin: ∆3.0 ± 0.3 mmHg, P=0.02; TVC, Rest: ∆‐5.2 ± 0.8; Insulin: ∆‐3.1 ± 0.7 mL/min/mmHg, P=0.05). However, it is important to note that 15 ± 5% of MSNA bursts exhibited amplitudes greater than that which existed at rest and overall during hyperinsulinemia ~50% of all MSNA bursts were comparable or greater in amplitude to the largest bursts present at rest. Collectively, these preliminary findings suggest that during hyperinsulinemia, sympathetic transduction for a given burst amplitude is attenuated while ‘net’ sympathetic transduction remains unchanged due to the generation of larger MSNA bursts.