Cardiovascular, neuroendocrine and renal effects of acute hyperinsulinemia in healthy men

The clinical association between hyperinsulinemia, insulin resistance and essential hypertension suggests that aspects of glucose metabolism are involved in blood pressure regulation. It has been suggested that hyperinsulinemia in the presence of glucose homeostasis may produce sympathetic overactivity and increased sodium retention; two mechanisms by which chronic hyperinsulinemia may be etiologically related to the development of hypertension. Using a sample of 16 healthy men, we performed euglycemic insulin clamps (40 mU/m$\sp2$/min) to assess cardiovascular, neurohumoral and renal effects of acute physiologic hyperinsulinemia during baseline and behavioral challenge conditions (Speech Prep Task, Speech Talk Task and Mirror Tracing Task). Each task was performed twice: once during conditions of normoinsulinemia and once during hyperinsulnemia (i.e., the steady-state portion of the clamp). Assessments included urinary sodium, plasma catecholamines (CATS), plasma potassium (K), blood pressure (BP) and heart rate (HR). Cardiac output (CO), total peripheral resistance (TPR) and the Heather Index (HI) estimate of contractility were derived from the impedance cardiogram. Insulin sensitivity was assessed during the clamp using total glucose metabolized (M) and metabolic clearance rate for insulin (MCR). The insulin/glucose ratio (I/G) obtained from oral glucose tolerance tests (OGTT\u27s) was also used as an index of insulin sensitivity.Under steady-state conditions, mean plasma insulin was 107.3 mU/ml (CV = 16.7%). Acute hyperinsulinemia under euglycemic clamp conditions produced an increase in sympathetic activation, as indicated by increases in plasma NE and the HI estimate of contractility and a decrease in sodium excretion. Our correlational data indicated that the sympathoexcitatory effects of insulin (i.e., increases in NE, cardiac contractility (HI) and cardiac function (SBP, CO)) were most evident in the most insulin sensitive subjects.The patterns of response to tasks were quite similar across insulin conditions, suggesting that the effects of task were robust in the presence of a pharmacologic challenge. To summarize, all tasks produced an increase in SBP, DBP and HR. During both speech tasks there was also an increase in CO and NE. Mirror tracing produced an increase in TPR and a decrease in SV.The hypothesis that there would be greater cardiovascular responsivity to tasks during hyperinsulinemia was supported with respect to SBP during Speech Prep, but was not supported with respect to the other variables during this task or with respect to any variables during the other two tasks. Correlational data indicated that greater vascular and contractility responses to tasks and to the combined effects of insulin and tasks were observed in the least insulin sensitive subjects.Altogether, these data suggest that an association between insulin resistance and elevated blood pressure is not revealed under baseline clamp conditions, but is revealed under conditions of task-mediated sympathetic arousal and combined task and insulin-mediated sympathetic arousal