Nutritional Modulation of Blood Pressure Regulation by the Autonomic Nervous System
Open Access
- Author:
- Florian, John P
- Graduate Program:
- Physiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 21, 2007
- Committee Members:
- James Anthony Pawelczyk, Committee Chair/Co-Chair
David Nathan Proctor, Committee Member
Mihai Covasa, Committee Member
Nancy Williams, Committee Member
Mosuk Chow, Committee Member - Keywords:
- blood pressure
sympathetic nervous system
free fatty acids
caloric restriction
hypertension
spaceflight - Abstract:
- Cardiovascular function is modulated by changes in caloric intake and by metabolic factors in plasma such as free fatty acids (FFA). However, the mechanisms underlying the associated cardiovascular responses are unclear. The purpose of this series of experiments was to investigate the neural mechanisms underlying the altered control of blood pressure (BP) resulting from caloric/fat restriction and elevated FFA concentrations. In the first study we investigated the impact of caloric restriction (CR) on cardiovascular function. Astronauts consume fewer calories during spaceflight and return to earth with an increased risk of orthostatic intolerance. Whether a caloric deficiency modifies orthostatic responses is not understood. Thus, we determined the effects of a hypocaloric diet (25% CR) during 6° head down bedrest (BR; an analog of spaceflight) on autonomic neural control during lower body negative pressure (LBNP). Nine healthy young men participated in a randomized crossover BR study, consisting of four (2 weeks each) interventions (normocaloric BR (NB), normocaloric ambulatory (NA), hypocaloric BR (HB), hypocaloric ambulatory (HA)), each separated by 5 months. Muscle sympathetic nerve activity (MSNA), heart rate (HR), and arterial pressure were recorded before, during, and after 3 consecutive stages (7 min each) of LBNP (-15, -30, -45 mmHg). Caloric and posture effects were compared using two-way ANOVA with repeated measures. Both BR and CR were associated with lower systolic BP during LBNP (p<.01); however, HR responses were directionally opposite (i.e., increase with BR, decrease with CR). Survival analysis revealed a significant reduction in orthostatic tolerance (OT) following CR (p=0.03). Caloric restriction modifies autonomic responses to LBNP, which may decrease OT after spaceflight. The second study employing combinations of BR and CR tested the hypothesis that a caloric deficit diminishes the pressor response to static exercise and noxious cold stress. Nine healthy young men participated in a randomized crossover BR study, consisting of four, two-week interventions (HA, HB, NA, NB), each separated by 5 months. HR, arterial pressure, and MSNA were recorded before, during, and after static handgrip HG (40% of maximum voluntary contraction to fatigue), post-exercise muscle ischemia (forearm occlusion), and the cold pressor test. Bedrest and nutritional combinations were compared using two-way ANOVA with repeated measures. HR, MSNA, and the change in systolic BP during HG were attenuated with CR. CR was associated with a higher diastolic BP during cold pressor; however, HR was directionally opposite (i.e., increase with BR, decrease with CR). Therefore, CR, but not BR, severely attenuates autonomic responses to static exercise. The third study tested the hypothesis that acute elevation of FFA activates the sympathetic nervous system (SNS). Previous studies have shown that acute increases in plasma FFA raise systemic vascular resistance (SVR) and BP. However, these studies fail to distinguish between central nervous system (CNS) mechanisms that raise sympathetic activity and paracrine mechanisms that increase SVR directly independent of CNS involvement. On 2 days separated by at least 2 wks 17 lean, healthy volunteers (10M/7F; 22±1 yrs; BMI: 23±1 kg/m2; mean±SEM) received a 4-hr iv infusion of Intralipid 20% or placebo (single-blind, randomized, balanced order). MSNA, HR, BP (brachial auscultation), and cardiac output (Q, C2H2 rebreathing) were measured before and throughout infusion. The change in HR (+8.2±1.0 vs. +2.4±1.2 beats/min), systolic BP (+14.0±1.6 vs. +3.2±2.5 mmHg), and diastolic BP (+8.2±1.0 vs. -0.1±1.7 mmHg) was significantly greater after the 4-hr infusion of Intralipid vs. placebo (p<.001). The change in BP with Intralipid resulted from an increase in SVR (mean BP/Q; p<0.001) vs. baseline, without a change in Q. MSNA burst frequency increased during Intralipid infusion vs. baseline (+4.9±1.3 bursts/min; p<0.05), and total MSNA (frequency * amplitude) was augmented 65% (p<0.001), with no change during placebo infusion. Lipid infusion increased insulin, aldosterone, and F2-isoprostanes, but not leptin, concentrations. The concomitant increases in BP, MSNA, and SVR suggest that central sympathetic activation contributes to the pressor response to FFA. The fourth study tested the hypothesis that aging exacerbates the sympathetic and cardiovascular responses to elevated FFA. The objectives of this study were to characterize the cardiovascular, neural, and endocrine response to acute elevation of FFA. Seventeen healthy older volunteers (7M/10F; 69±1 yrs; BMI 24±0 kg/m2) received a 4-hr iv infusion of Intralipid 20% or placebo (single-blind, randomized, balanced order) on 2 different days separated by at least 2 wks. MSNA, HR, BP (brachial auscultation), Q (C2H2 rebreathing), leptin, insulin, aldosterone, angiotensin II, and F2-isoprostanes were measured. The change in HR (+8.8±0.9 vs. +3.0±0.9 beats/min), systolic BP (+13.9±2.2 vs. +6.6±2.4 mmHg), and diastolic BP (+7.4±1.5 vs. +1.3±0.8 mmHg) was significantly greater after the 4-hr infusion of Intralipid vs. placebo (p<.001). The increase in BP with Intralipid resulted from variable fluctuations in SVR (mean BP/Q) and Q. MSNA burst frequency increased during Intralipid infusion vs. baseline (+6.7±1.6 bursts/min; p<0.05), and total MSNA (frequency * amplitude) was augmented 45% (p<0.001), with no change during placebo infusion. Lipid infusion increased insulin (+40%), aldosterone (+50%), and F2-isoprostanes (+80%), but not leptin, concentrations. Direct vascular mechanisms and central sympathetic activation contribute to the pressor response to FFA; this response is not different compared to previous studies in a younger population. The results of these studies suggest that nutritional/metabolic factors alter autonomic control of the cardiovascular system. Specifically, moderate caloric/fat restriction diminishes BP control during orthostatic stress and static exercise. Conversely, acute elevation in FFA concentration increases BP by activating the central nervous system, and the response to FFA is not different in older individuals.