title: Treatment of muscle mechanoreflex dysfunction in hypertension: effects of L-arginine dialysis in the nucleus tractus solitarii.
abstract: What is the central question of this study? Does increasing NO production within the nucleus tractus solitarii (NTS) affect mechanoreflex function in normotensive and hypertensive rats?What is the main finding and its importance? Dialysis of 1 μm l-arginine, an NO precursor, within the NTS significantly attenuated the pressor response to muscle stretch in normotensive and hypertensive rats. In contrast, 10 μm l-arginine had no effect in normotensive animals, while increasing and decreasing the pressor and tachycardic responses to stretch, respectively, in hypertensive rats. This suggests that increasing NO within the NTS using lower doses of l-arginine can partly normalize mechanoreflex overactivity in hypertensive rats, whereas the effects of larger doses are equivocal. The blood pressure response to exercise is exaggerated in hypertension. Recent evidence suggests that an overactive skeletal muscle mechanoreflex contributes significantly to this augmented circulatory responsiveness. Sensory information from the mechanoreflex is processed within the nucleus tractus solitarii (NTS) of the medulla oblongata. Normally, endogenously produced nitric oxide within the NTS attenuates the increase in mean arterial pressure (MAP) induced by mechanoreflex stimulation. Thus, it has been suggested that decreases in NO production in the NTS underlie the generation of mechanoreflex dysfunction in hypertension. Supporting this postulate, it has been shown that blocking NO production within the NTS of normotensive rats reproduces the exaggerated pressor response elicited by mechanoreflex activation in hypertensive animals. What is not known is whether increasing NO production within the NTS of hypertensive rats mitigates mechanoreflex overactivity. In this study, the mechanoreflex was selectively activated by passively stretching hindlimb muscle before and after the dialysis of 1 and 10 μm l-arginine (an NO precursor) within the NTS of decerebrate normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Stretch induced larger elevations in MAP in SHRs compared with WKY rats. In both groups, dialysis of 1 μm l-arginine significantly attenuated the pressor response to stretch. However, at the 10 μm dose, l-arginine had no effect on the MAP response to stretch in WKY rats, while it enhanced the response in SHRs. The data demonstrate that increasing NO availability within the NTS using lower doses of l-arginine partly normalizes mechanoreflex dysfunction in hypertension, whereas higher doses do not. The findings could prove valuable in the development of treatment options for mechanoreflex overactivity in this disease.
authors.affiliation: Department of Bioengineering, University of Texas Southwestern Medical Center, Dallas, TX 75390-9174, USA.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Leal
authors.forename: Jere H
authors.initials: JH
authors.lastname: Mitchell
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D017551:Microdialysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012026:Reflex, Stretch / Q000187:drug effects*; D017552:Solitary Nucleus / Q000503:physiopathology*
chemical_list: D001120:Arginine