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Skeletal Muscle Reflex‐Induced Dysregulation of Sympathetic Nerve Activity in Type 1 Diabetic Rats
Author(s) -
Kim Han-Kyul,
Ishizawa Rie,
Hotta Norio,
Iwamoto Gary,
Vongpatanasin Wanpen,
Mitchell Jere,
Smith Scott,
Mizuno Masaki
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04746
Subject(s) - medicine , reflex , endocrinology , blood pressure , sympathetic nervous system , stimulation , skeletal muscle , mean arterial pressure , pressor response , heart rate
The pressor response to physical exercise is exaggerated in the early stages of type 1 diabetes mellitus (T1DM). This augmented blood pressure (BP) response has been further shown to be mediated by an overactive skeletal muscle exercise pressor reflex (EPR). However, whether alterations in sympathetic responsiveness contribute to this EPR overactivity is unknown. The purpose of this study was to test the hypothesis that the potentiated BP response to exercise in T1DM is mediated by EPR‐induced sympathetic overactivity. Sprague‐Dawley rats were intraperitoneally given either 50 mg/kg streptozotocin (T1DM) or saline (control). We measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to activation of the EPR, as well as its functional components, the mechanoreflex and metaboreflex, in decerebrate animals at 1–3 weeks after administration. Compared to control rats, selective activation of the EPR evoked significantly greater increases in RSNA (Δ = 58±7 vs. 96±15 %, P<0.05 ) and MAP (Δ = 11±2 vs. 33±5 mmHg, P<0.05 ) in T1DM rats. The sympathetic and pressor responses to the individual stimulation of the mechanoreflex and metaboreflex were also significantly larger in T1DM animals than in control animals ( P<0.05 ). These findings suggest that in untreated T1DM, abnormally large muscle reflex‐evoked sympathetic overactivity contributes significantly to exaggerations in BP during exercise. Importantly, the results implicate sympathetic overactivity as a potential therapeutic target for improving/preventing the abnormally high BP response to exercise in T1DM. Support or Funding Information The Southwestern School of Health Professions Interdisciplinary Research Grant Program, the Lawson & Rogers Lacy Research Fund in Cardiovascular Disease and the JSPS KAKENHI JP17K01769