EFFECTS OF GHRELIN INFUSION ON SYMPATHETIC NERVOUS SYSTEM ACTIVITY IN HUMANS: PP.32.256

Abstract

Ghrelin is a recently discovered GH-releasing peptide secreted by the stomach with effects on appetite and cardiovascular regulation. Animal studies suggest that ghrelin acts centrally to decrease the activity of the sympathetic nervous system (SNS) and may have a role in mediating behavioural responses to stress. To investigate the effects of ghrelin in humans, we gave 9 lean healthy men (age 21 ± 0.3 years) an intravenous infusion of human ghrelin (5pmol/kg/min for 1 hour) and saline in a randomized fashion. Ghrelin elicited a small decrease in systolic and diastolic blood pressure (-12 mmHg vs -4 mmHg for systolic and -12 ± 1 mmHg vs -6 ± 1 mmHg for diastolic, during ghrelin and saline infusion respectively, P < 0.05) without a significant change in heart rate or cardiac output. Ghrelin infusion resulted in a marked increase in muscle sympathetic nervous activity (MSNA), measured by microneurography (from 18 ± 2 to 26 ± 4 bursts per min, P < 0.05) while no change occurred during saline infusion (from 18 ± 2 to 17 ± 1 bursts per min). Ghrelin, but not saline, induced a rise in plasma glucose concentration (from 4.4 ± 0.1 to 4.8 ± 0.1 mmol/l, P < 0.05). A stress test consisting of 5-min of forced mental arithmetic was performed following the infusion of saline and ghrelin. During saline, stress induced a significant change in mean blood pressure (+24 mmHg), heart rate (+21 bpm) and MSNA (+33%, P < 0.05). During ghrelin infusion, the changes in heart rate were similar but the changes in blood pressure and MSNA were significantly reduced compared with saline infusion (+18 mmHg and -9% in MSNA, P < 0.05). These results indicate that in healthy human, ghrelin-induced decrease in blood pressure is accompanied by a marked increase, rather than a decrease, in SNS activity. We hypothesize that ghrelin activates the SNS through baroreceptor unloading as a result of a peripheral vasodilatory effect rather than by affecting the central nervous system. Furthermore, ghrelin may contribute to the stress induced cardiovascular responses.