Effect of Cortisol on Muscle Sympathetic Nerve Activity in Pima Indians and Caucasians

Abstract

The hypothalamo-pituitary-adrenal axis and sympathetic nervous system (SNS) interact to maintain cardiovascular and metabolic homeostasis, especially during stress. Pima Indians have a low SNS activity, which may contribute to both their increased risk of obesity and reduced risk of hypertension. Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol and muscle SNS activity [muscle sympathetic nervous system activity (MSNA), microneurography] in 58 males [27 Pimas/31 Caucasians]. Seven Pimas and 12 Caucasians were randomized to a double-blind, placebo-controlled, cross-over study to examine the effect of overnight partial chemical adrenalectomy (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P < 0.006). No correlation was found between fasting cortisol and basal MSNA. Administration of metyrapone did not lead to significant changes in MSNA. In response to a hydrocortisone infusion, MSNA decreased in Pima Indians (P = 0.03) but not in Caucasians (P = 0.7). Our data indicate that the low SNS activity that predisposes Pima Indians to obesity is not due to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population.

Acute hydrocortisone administration reduces cardiovagal baroreflex sensitivity and heart rate variability in young men

“…sino-atrial node or smooth muscle) and efferent nerves (Chapleau & Abboud, 2001). The cortisol-induced increase in HR and systolic BP found in our study, as well as in previous studies (Takahashi et al 1983;Dodt et al 2000;Scheuer & Mifflin, 2001;Vozarova et al 2003;Heindl et al 2006), may suggest a centrally-mediated resetting of the baroreflex. A rise in systolic BP would be expected to increase baroreceptor firing resulting in a compensatory fall in HR and inhibition of sympathetic outflow to the peripheral vasculature.…”

“…Glucocorticoids can up-regulate cardiac β 1 -adrenergic receptor sensitivity (Nishimura et al 1997), which can potentiate the effects of circulating epinephrine and norepinephrine. In prior studies, resting muscle sympathetic nerve activity decreased (Dodt et al 2000) or did not change (Vozarova et al 2003;Heindl et al 2006) following glucocorticoid administration. Peripheral vasoconstriction probably does not contribute to the rise in systolic BP because LVC remained unaffected in the present study and diastolic BP did not increase.…”

“…; Scheuer & Mifflin, ; Vozarova et al . ; Heindl et al . ), may suggest a centrally‐mediated resetting of the baroreflex.…”

Chronic but Not Acute Hydrocortisone Treatment Shifts the Response to an Orthostatic Challenge towards Parasympathetic Activity

“…In contrast, CRH increases sympathetic activity, but does not significantly change parasympathetic activity [34]. An acute release of cortisol prevents sympathoexcitation during stress in Pima Indians but not in Caucasians [35]. In line with these findings, in our study, chronic hydrocortisone treatment was associated with non-significantly decreased sympathetic activity.…”