Skeletal Muscle Reflex Induced Fos Expression within the NTS of Normotensive and Hypertensive Rats

Abstract

In hypertension, the cardiovascular response to exercise is exaggerated. Evidence suggests this heightened response is mediated by the skeletal muscle exercise pressor reflex (EPR). The mechanically-sensitive component of the EPR, the muscle mechanoreflex (MMR), contributes significantly to EPR overactivity in this disease. Sensory information from the EPR and MMR is processed within the nucleus tractus solitarius (NTS) of the medulla oblongata. To date, it has yet to be determined whether the number of NTS neurons activated by the EPR and MMR are altered in hypertension. Making this determination is important as changes in neuronal activation within the NTS by either of these reflex inputs may underlie their overactivity in hypertension. PURPOSE: Neurons excited by the EPR and MMR express Fos, the protein product of the early response gene c-fos. Immunohistochemical labeling of Fos is an effective means of identifying neurons activated by muscle reflexes. Using this method, we sought to determine the location and quantity of neurons activated by the EPR and MMR within the NTS. METHODS: In male decerebrate normotensive Wistar-Kyoto (WKY; n=3) and spontaneously hypertensive rats (SHR; n=5), we selectively activated the MMR by passively stretching hindlimb muscle (30 s stretch followed by 30 s relaxation) for 1 h. Similarly, the EPR was activated in separate SHR (n=3) by electrically inducing static contraction of the hindlimb. After a 1 h recovery period, animals were fixed and medullary tissue obtained. Tissue, 1mm caudal and rostral to the calamus scriptorius, was stained for Fos expression. RESULTS: The medial NTS lateral to the calamus scriptorius (-14.40 Bregma) expressed the largest amount of Fos in all animals. In this area, the quantity of neurons expressing Fos in response to stretch was greater in SHR (49 + 8) than WKY (27 + 9). Within SHR, Fos expression in response to contraction (104 + 21) was larger compared to stretch. CONCLUSIONS: The findings indicate that the medial NTS may be critical for processing afferent information from skeletal muscle reflexes. The data further suggest that the number of NTS neurons activated by muscle reflexes in hypertension may be enhanced which could contribute to the exaggerated cardiovascular response to exercise characteristic of this disease. Supported by NIH HL-088422