Centrally Acting Perindopril Attenuates the Exercise Induced Increase in Muscle Sympathetic Nerve Activity during Heavy Dynamic Exercise

Central angiotensin II (Ang II) linked free radical (FR) production scavenges nitric oxide (NO) enabling an increased central sympathetic neural outflow (SNA). The pathophysiological increase in Ang II linked FR production is recognized as a major mechanism involved in neurogenic hypertension. During exercise, there is a physiological increase in Ang II and muscle sympathetic nerve activity (MSNA) in direct relation to increasing exercise intensity. We tested the hypothesis that the exercise induced increase in Ang II linked FR production and MSNA activity during exercise is located within the brain. Six healthy subjects performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of two different lipid soluble Angiotensin converting enzyme inhibitors ((ACEi) Perindopril (PER) - highly lipid soluble; Captopril (CAP) non-lipid soluble)) and/or placebo (PL). Repeated measurements of whole venous blood, MSNA, and mean arterial pressures (MAP) were obtained at rest and during steady-state heavy intensity exercise at heart rates (HR) of 120 bpm (e120). Peripheral venous superoxide concentrations as measured by electron paramagnetic resonance (EPR) were not significantly altered at rest (P≥0.4) and during E120 by the ACE inhibitors (P≥0.07). Likewise, baseline MSNA (PL, 25 ± 1.5 bust/min; CAP, 21 ± 0.7 bust/min; PER, 25 ± 0.7 bust/min) and MAP (PL, 86 ± 2.8 mmHg vs. CAP, 84 ± 2.6 mmHg; PER, 84 ± 0.7 mmHg) were unchanged at rest (P≥0.1; P≥0.8 respectively). However, during E120 central acting PER attenuated the increases in MSNA and MAP, increasing only 15±6% for MAP and 24±8% for MSNA when compared to PL (26 ± 6% MAP; 57±16% MSNA; P\u3c0.05) and CAP (26±4%MAP; 69±13%MSNA P\u3c0.05). From these data we conclude that centrally acting PER attenuated the central increase in the exercise induced Ang II linked free radical production resulting in an increased central NO activity induced reduction in MSNA during heavy intensity dynamic exercise

Antioxidants Attenuate the Exercise Induced Resetting of the Arterial Baroreflex in Healthy Human Subjects: Implications for Exercise Induced Hypertension

Patients with Exercise-induced-Hypertension (EiHT) exhibit exaggerated increases in arterial pressure at the onset of exercise which may prevent EiHT patients from participating in exercise training programs. EiHT is thought to occur due to dysregulated resetting of the arterial baroreflex (ABR). Prior studies in animal models demonstrate that reactive oxygen species (ROS) generated in the brainstem scavenge the sympathoinhibitory function of central Nitric Oxide (NO) and, thereby enable ABR resetting of the operating point (OP) pressure and hypertension. We tested the hypothesis that a centrally and peripherally active antioxidant cocktail (CT; composed of Vitamin E and C with Co-Q10) will attenuate the exercise induced resetting of the ABR‘s centering point (CP) and OP pressures compared to the same exercise intensity performed with a vehicle placebo (PL). Seven healthy human subjects were recruited and performed 700 back-supported semi-recumbent dynamic leg exercise at moderate (HR at 120 beats per minute: e120) and heavy (HR at 150 beats per minute: e150) intensities. Mean arterial pressure (MAP) was continuously recorded using photoplethysmography at the finger, while HR was recorded via a three lead electrocardiogram (ECG). On experimental day 1, subjects were either given the CT or PL 1 hr. (time of peak plasma concentrations) prior to the start of exercise. On a separate experiment day 2, the subjects repeated the same exercise intensity protocol with the other test article (CT or PL) in a randomized repeated measures design. During exercise with the PL ingestion, the CP of the ABR was reset to higher MAPs from rest to e120 (100 ± 3 mm Hg to 121 ± 3 mm Hg, P\u3c0.02) but not e150 (113 ± 3 mm Hg, P=0.15). The absence of resetting at the higher work intensity was likely due to cardiovascular drift (decreasing MAP). Ingestion of the CT prior to the exercise protocols prevented the increase of the CP to higher MAPs from rest to e120 and e150 (rest: 97 ± 3 mm Hg, e120: 106 ± 3 mm Hg, e150: 106 ± 3 mm Hg, P \u3e0.21). Furthermore, the OP- pressure of the ABR was attenuated with CT ingestion compared to PL at e120 (placebo e120: 116 ± 0.8 mm Hg, CT e120: 111 ± 0.8 mm Hg, P = 0.04). These data: (a) confirm that centrally derived ROS contribute to exercise induced ABR resetting; and (b) indicate that EiHT could be treated by ingestion of an anti-oxidant cocktail prior to the start of exercise

Commentaries on Viewpoint: The ongoing need for good physiological investigation: Obstructive sleep apnea in HIV patients as a paradigm

The final publication is available via http://dx.doi.org/10.1152/japplphysiol.00989.2014[Abstract] The intriguing paradigm put forth by Darquenne et al. (3) highlighted that improved therapy against human immunodeficiency virus (HIV) has come at the cost of elevated rates of chronic diseases, such as obstructive sleep apnea (OSA) and obesity, during the highly active antiretroviral therapy (HAART) era.Ministerio de Economía y Competitividad; TIN2013-40686-P