Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans

• Published in: The Journal of physiology 2010-09, Vol.588 (18), p.3593-3603
• Main Authors: Young, Colin N., Deo, Shekhar H., Chaudhary, Kunal, Thyfault, John P., Fadel, Paul J.
• Format: Article
• Language: English
• Subjects: Adult; Arteries - drug effects; Arteries - physiology; Baroreflex - physiology; Glucose Clamp Technique; Humans; Insulin - pharmacology; Integrative; Male; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Sympathetic Nervous System
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2010.191866

Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (Δ34 ± 6 uIU ml−1; P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex‐MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: −3.29 ± 0.54 baseline vs.−5.64 ± 0.67 bursts (100 heart beats)−1 mmHg−1 at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (Δ42 ± 6 μIU ml−1; P < 0.05), while glucose was maintained constant, arterial baroreflex‐MSNA gain was similarly enhanced (e.g. burst incidence gain: −2.44 ± 0.29 baseline vs.−4.74 ± 0.71 bursts (100 heart beats)−1 mmHg−1 at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex‐MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA. Arterial baroreceptors are critical for the regulation of blood pressure (BP). These receptors are stretch sensitive and respond to beat‐to‐beat changes in BP by altering parasympathetic and sympathetic neural outflow in order to bring BP back to its original value. Studies have indicated that the ability of the arterial baroreflex to alter sympathetic nerve activity is essential for its regulation of BP. In the current study, we show, for the first time in healthy humans, that physiological increases in plasma insulin, the hormone necessary for the uptake of glucose, enhances the sensitivity of arterial baroreflex control of sympathetic nerve activity. Thus, aside from its important role in controlling