Voluntary Wheel Exercise Training Decreases Arterial Pressure in Two Kidney‐One‐Clip Hypertensive Rats Independent of GABAergic Mechanisms in Paraventricular Nucleus

Abstract

Exercise training (ExT) decreases mean arterial pressure (MAP) and heart rate (HR) in humans and in rat models of hypertension, but its effect on angiotensin II (Ang II)-dependent two kidney-one clip (2K-1C) hypertension has not been studied. Circulating Ang II acts upon circumventricular areas of the brain that project to paraventricular nucleus (PVN) whose efferent projections can influence baroreflex activity and sympathetic tone. We tested the hypothesis that six weeks of voluntary wheel ExT in 2K-1C rats would decrease MAP, HR and RSNA and that this effect is mediated via enhanced GABAergic and nitritergic mechanisms in the PVN. Awake, unrestrained sedentary (SED) or ExT sham and 2K-1C rats were studied before and after microinjection of 200 pmol bicuculline or 200 μg L-NAME into PVN. Resting MAP and HR was similar in sham ExT and SED rats, but MAP was lower in ExT vs SED 2K-1C rats (145 ± 4 vs 179 ± 11 mmHg, p < 0.05) as was HR. Bicuculline evoked roughly a two-fold greater rise in MAP, HR and RSNA in sham ExT vs SED rats (p < 0.05). In contrast, the rise in RSNA was attenuated in the ExT vs SED 2K-1C rats. The responses of the 2K-1C ExT rats most closely resembled those of the SED sham rats. Blockade of nitric oxide production did not alter responses in any of the groups. Thus, voluntary wheel ExT in sham clipped rats has a sympathoinhibitory effect mediated, at least in part, via GABAergic mechanisms in the PVN. In 2K-1C rats at a time when their elevated arterial pressure is Ang II dependent, ExT significantly decreases MAP and HR but these effects appear to be independent of GABA receptors in the PVN.