Effect of acute hyperlipidemia on autonomic and cardiovascular control in humans

Abstract

Blood lipids may detrimentally affect autonomic and circulatory control. We tested the hypotheses that acute elevations in free fatty acids and triglycerides (acute hyperlipidemia) impair baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA: sympathetic BRS), increase MSNA at rest, and augment physiological responses to exercise. Eighteen young adults were examined in this randomized, double-blinded, and placebo-controlled study. BRS was determined using the modified Oxford technique before (pre) and 60 min (post) after initiating infusion of Intralipid (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (experimental; n = 12) to induce acute hyperlipidemia, or saline (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (control; n = 6). Responses to isometric handgrip to fatigue (IHG) were also determined. Blood pressure increased more (P < 0.05) in experimental than control subjects during the infusion. MSNA at rest (14 +/- 2 vs. 11 +/- 1 bursts/min), cardiovagal (19.8 +/- 1.8 vs. 19.1 +/- 2.4 ms/mmHg pre and post, respectively) and sympathetic BRS (-5.5 +/- 0.6 vs. -5.2 +/- 0.4 au x beat(-1) x mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by acute hyperlipidemia (pre vs. post) in experimental subjects. Similarly, MSNA at rest (10 +/- 2 vs. 12 +/- 2 bursts/min), cardiovagal (22.1 +/- 4.0 vs. 21.0 +/- 4.6 ms/mmHg) and sympathetic BRS (-5.8 +/- 0.5 vs. -5.5 +/- 0.5 au x beat(-1) x mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by the infusion in control subjects. These data do not provide experimental support for the concept that acute hyperlipidemia impairs reflex cardiovagal or sympathetic regulation in humans.

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

“…To date, limited findings suggest [6,8], but have not definitively proven [13,14], a link between the rise in BP and sympathetic activation. In normotensive rats,…”

“…It is difficult to reconcile these disparate findings, particularly in the absence of a control group and haemodynamic results in the latter study. More recently, a study assessing baroreflex function did not show a change in sympathetic activation during a 2-h lipid infusion [14]; however, the limited duration of that study may have precluded a complete sympathetic response to elevated NEFA concentrations. The increase in burst frequency (approx.…”

“…This is surprising given the evidence that some forms of hypertension with obesity and high-fat diets may be neurogenically mediated [11,12]. Studies of various lengths in normotensive rats and humans have shown that acutely elevating the NEFA concentration increases [5,8], decreases [13] or does not change [14] sympathetic activity. However, probably due to indirect measures of sympathetic activity [i.e.…”

“…However, probably due to indirect measures of sympathetic activity [i.e. NA (noradrenaline) concentrations] [5,8,13] or insufficient duration of previous studies [14], it remains unclear whether NEFAs activate the SNS.…”

Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension

“…After control measurements, obesity hypertension was produced by feeding a high-fat diet for 28 days before reducing fat intake to maintain body weight for the remainder of the study. The experimental protocol consisted of 1) control, days 1-3; 2) days 4 -31, high fat (development of obesity and hypertension); 3) days 32-63, reduced fat (established obesity hypertension); 4) days [35][36][37][38][39][40][41], baroreflex activation (1 wk); 5) days [42][43][44][45][46][47][48], recovery (1 wk); 6) day 49, surgical bilateral renal denervation by procedures previously used in our laboratory (33); and 7) day 63, end of study (2 wk after renal denervation).…”