Increased Muscle Sympathetic Nerve Activity with Acute Hyperinsulinemia: Role of Insulin-stimulated Peripheral Vasodilation and the Response of the Arterial Baroreflex

OBJECTIVE: Hyperinsulinemia elicits an increase sympathetic nervous system activity directed toward skeletal muscle (muscle sympathetic nerve activity, MSNA). The insulin-mediated increase in MSNA is primarily attributed to its effect within the central nervous system. In addition to direct central effects, insulin also elicits peripheral vasodilation, which may further increase MSNA via arterial baroreflex-mediated mechanisms in order to maintain blood pressure (BP). Herein we examined the contribution of insulin-induced peripheral vasodilation and role for the arterial baroreflex in the MSNA response to hyperinsulinemia. We hypothesized that rescuing peripheral resistance with co-infusion of the vasoconstrictor phenylephrine would attenuate the MSNA response to hyperinsulinemia. We further hypothesized the insulin-mediated increase in MSNA would be recapitulated with another vasodilator (sodium nitroprusside, SNP). METHODS: In 33 healthy adults (28M/5F, 28±1 yrs, BMI 25.0±0.5 kg/m2 ) MSNA (microneurography) and BP (Finometer/brachial catheter) were measured, and total peripheral resistance (TPR, ModelFlow) was calculated at rest and during intravenous insulin (n=20) or SNP (n=13) infusion. A subset of participants receiving insulin (n=7) were co-infused with phenylephrine. Spontaneous arterial baroreflex sensitivity was determined over 5-min at baseline and during pharmacological intervention(s). RESULTS: Insulin infusion increased MSNA (p=0.05) and decreased TPR (p<0.05), with no effects on arterial baroreflex sensitivity or BP (p>0.05). Co-infusion with phenylephrine returned MSNA and TPR to baseline, with no effect on baroreflex sensitivity (p>0.05). Similar to insulin, SNP increased MSNA (p<0.01) and decreased TPR (p<0.05), with no effect on baroreflex sensitivity (p>0.05). CONCLUSIONS: Present findings reveal that acute hyperinsulinemia increases MSNA without a change in arterial baroreflex sensitivity in healthy men and women. Insulin-mediated increases in MSNA are lost with co-infusion of phenylephrine and can be recapitulated with infusion of SNP. Results support a dynamic interplay between central and peripheral mechanisms during hyperinsulinemia to increase MSNA and maintain BP. © FASEB.