Sympathetic Nerve Responses to Activation of Chemically-Sensitive Skeletal Muscle Afferent Fibers in Hypertensive Rats

Abstract

The pressor response to exercise is exaggerated in hypertension. Recent evidence suggests that this heightened blood pressure (BP) responsiveness is mediated, in part, by the skeletal muscle metaboreflex (SMM). However, the mechanism by which the SMM drives this abnormally large increase in BP during physical activity remains to be elucidated. The SMM is activated by stimulation of chemically-sensitive afferent fibers (primarily group IV neurons) in skeletal muscle. Normally, stimulation of this group of afferent neurons by the metabolic by-products of muscle work acutely increases sympathetic nerve activity (SNA). Thus, we hypothesized that activation of chemically-sensitive afferent fibers in muscle produces exaggerated increases in SNA resulting in abnormally large elevations in BP in hypertension. PURPOSE: To determine the BP and SNA responses to activation of chemically-sensitive muscle afferent fibers in hypertension. METHODS: Chemically-sensitive afferent fibers were selectively activated by administering capsaicin (CAP) into the hindlimb arterial supply of normotensive Wistar-Kyoto (WKY, n = 5) and spontaneously hypertensive (SHR, n = 7) decerebrate rats. CAP is known to primarily stimulate the group IV afferent neurons associated with the SMM. RESULTS: Five doses of CAP were given: 0.01, 0.03, 0.1, 0.3, and 1.0 μg/100 μl. In WKY, these doses increased mean arterial pressure (from baseline) by 13±3, 10±4, 17±5, 24±6, and 40±9 mmHg, respectively. The BP responses to these doses of CAP were consistently larger in SHR (22±12, 23±7, 18±4, 27±5, and 48±7 mmHg, respectively). Renal SNA responses to CAP were variable being greater in SHR in some instances but not all. For example, the 0.3μg/100 μl dose of CAP induced increases (from baseline) in renal SNA of 77.3 ± 21.0% in WKY and 97.9 ± 24.6 % in SHR. In contrast, the 1.0μg/100 μl dose of CAP elevated SNA by 166.6 ± 48.2% in WKY and 137.5 ± 35.1% in SHR. CONCLUSIONS: The results suggest that activation of chemically-sensitive muscle afferent fibers evokes inconsistent exaggerations in SNA in hypertensive rats when compared to their normotensive counterparts. Although such changes in SNA may contribute to the heightened elevations in BP mediated by the SMM in hypertension, it is likely another unidentified mechanism also plays a role. Supported by NIH HL-088422