title: Progressive arteriolar vasoconstriction and fatigue during tetanic contractions of rat skeletal muscle are inhibited by α-receptor blockade.
abstract: Voluntary muscle contractions activate sympathetic efferent pathways. Using a fatiguing electrical stimulation protocol designed specifically to enhance sympathetically-mediated vasoconstrictor tone, we explored the temporal profile and mechanistic bases of the evoked vasoconstrictor response and its role in muscle fatigue. Spinotrapezius muscles of Wistar rats were exteriorized and stimulated tetanically (100 Hz, 6-8 V, stimulus duration 700 ms) every 3 s for 2.5 min. The extent and time course of diameter changes in arterioles (1A and 2A) and venules (1V and 2V) were determined after each of 10 discrete sets of muscle stimulation at 5-min intervals. At first, to compare the effect of stimulation parameters in this preparation, stimulations were performed with rectangular pulses of either 0.2- or 4-ms pulse duration. As expected the 0.2-ms pulse stimulation did not affect arteriolar diameter or muscle fatigability. In contrast, during and following 4-ms pulse stimulations, there was a surprising arteriolar vasoconstriction rather than the expected vasodilation. Arteriolar (but not venular) vasoconstriction (reduced arteriolar diameter by 38.6 ± 2.6% in the 10th set) increased progressively with muscle fatigue (to 29 ± 12% of initial tension in the 10th set) for the 4-ms pulse condition. Superfusion with the selective α1-adrenergic receptor antagonist prazosin (1 μM) and/or α2-adrenergic receptor antagonist rauwolscine (10 μM) abolished both the arteriolar vasoconstriction and significantly reduced fatigue (i.e., % initial tension, α1: 46.8 ± 10.3%; α2: 39.0 ± 5.8%; α1 + α2: 48.7 ± 16.3% in the 10th set; all P < 0.05 vs. control). We conclude that sequential bouts of contractions induce a progressively greater degree of α-adrenergic receptor-induced arteriolar (but not venular) vasoconstriction which contributes significantly to fatigue in this model.
authors.affiliation: Departments of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Chofu, Tokyo, 1828585, Japan.
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Inagaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.forename: David C
authors.initials: DC
authors.lastname: Poole
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kano
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology; D014699:Venules / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D011224:Prazosin