title: Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats.
abstract: The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20-50 μA in 10-μA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tibial nerve discharge during MLR stimulation significantly increased in an intensity-dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared with WKY across all stimulation intensities (e.g., at 50 μA, ΔRSNA: WKY 153 ± 31%, SHR 287 ± 42%; ΔMAP: WKY 87 ± 9 mmHg, SHR 139 ± 7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Integrative Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nan
authors.initials: N
authors.lastname: Liang
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Jere H
authors.initials: JH
authors.lastname: Mitchell
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, Texas; and masaki.mizuno@utsouthwestern.edu.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D017704:Baroreflex; D002319:Cardiovascular System / Q000503:physiopathology*; D003655:Decerebrate State; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005071:Evoked Potentials; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D008297:Male; D008636:Mesencephalon / Q000503:physiopathology*; D009043:Motor Activity; D005082:Physical Exertion; D011311:Pressoreceptors / Q000503:physiopathology; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors
keywords: arterial blood pressure; central command; exercise; hypertension; sympathetic nervous system