1. TRPV1 (Transient Receptor Potential Vanilloid 1) Sensitization of Skeletal Muscle Afferents in Type 2 Diabetic Rats With Hyperglycemia
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Rie Ishizawa, Masaki Mizuno, Norio Hotta, Wanpen Vongpatanasin, Jere H. Mitchell, Scott A. Smith, Gary A. Iwamoto, and Han-Kyul Kim
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medicine.medical_specialty ,endocrine system diseases ,TRPV1 ,TRPV Cation Channels ,Blood Pressure ,030204 cardiovascular system & hematology ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,Transient receptor potential channel ,0302 clinical medicine ,Ganglia, Spinal ,Physical Conditioning, Animal ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Neurons, Afferent ,Muscle, Skeletal ,Evoked Potentials ,Protein Kinase C ,Sensitization ,business.industry ,nutritional and metabolic diseases ,Skeletal muscle ,Rats ,Blood pressure ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Capsaicin ,business ,030217 neurology & neurosurgery - Abstract
The blood pressure response to exercise is exaggerated in type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain unclear. It is hypothesized that one mechanism mediating the potentiated cardiovascular response in T2DM is the sensitization of chemically sensitive afferent neurons by activation of metaboreceptors. To test this hypothesis, we examined transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced cardiovascular responses in vivo and muscle afferent discharge ex vivo in T2DM rats. Additionally, TRPV1 and protein kinase C (PKC) protein levels in dorsal root ganglia (DRG) subserving skeletal muscle were assessed. For 14-16 weeks, Sprague-Dawley rats were given either a normal diet (control) or high fat diet in combination with a low dose (35 and 25 mg/kg) of streptozotocin (T2DM). Administration of capsaicin, TRPV1 agonist, in hindlimb evoked significantly greater increases in mean arterial pressure and renal sympathetic neve activity in decerebrated T2DM than control. In a muscle-nerve preparation, the discharge to capsaicin exposure in group IV afferents isolated from T2DM was likewise significantly augmented at a magnitude that was proportional to glucose concentration. Moreover, the discharge to capsaicin was potentiated by acute exposure of group IV afferents to a high glucose environment. T2DM showed significantly increased phospholyrated-TRPV1 and −PKCα levels in DRG neurons as compared with control. These findings suggest that group IV muscle afferents are sensitized by PKC-induced TRPV1 overactivity in early-stage T2DM with hyperglycemia and, thereby, may contribute to the potentiated circulatory response to TRPV1 activation in the disease.
- Published
- 2021
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