title: Acute tetrahydrobiopterin supplementation attenuates sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of healthy rats.
abstract: Tetrahydrobiopterin (BH4) is an essential cofactor for the production of nitric oxide (NO) and supplementation with BH4 improves NO-dependent vasodilation. NO also reduces sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle. Thus, we hypothesized that supplementation with BH4 would blunt sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle. Sprague-Dawley rats (n = 15, 399 ± 57 g) were anesthetized and instrumented with an indwelling brachial artery catheter, femoral artery flow probe, and a stimulating electrode on the lumbar sympathetic chain. Triceps surae muscles were stimulated to contract rhythmically at 30% and 60% of maximal contractile force (MCF). The percentage change of femoral vascular conductance (%FVC) in response to sympathetic stimulations delivered at 2 and 5 Hz was determined at rest and during muscle contraction in control and acute BH4 supplementation (20 mg·kg(-1) + 10 mg·kg(-1)·h(-1), IA) conditions. BH4 reduced (P < 0.05) the vasoconstrictor response to sympathetic stimulation (i.e., decrease in FVC) at rest (Control: 2 Hz: -28 ± 5%FVC; 5 Hz: -45 ± 5%; BH4: 2 Hz: -17 ± 4%FVC; 5 Hz: -34 ± 7%FVC) and during muscular contraction at 30% MCF (Control: 2 Hz: -14 ± 6%FVC; 5 Hz: -28 ± 11%; BH4: 2 Hz: -6 ± 6%FVC; 5 Hz: -16 ± 10%) and 60% MCF (Control: 2 Hz: -7 ± 3%FVC; 5 Hz: -16 ± 6%FVC; BH4: 2 Hz: -2 ± 3%FVC; 5 Hz: -11 ± 6%FVC). These data are consistent with our hypothesis that acute BH4 supplementation decreases sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle.
authors.affiliation: Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Jendzjowsky
authors.affiliation: Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Just
authors.affiliation: Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kelvin E
authors.initials: KE
authors.lastname: Jones
authors.affiliation: Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Darren S
authors.initials: DS
authors.lastname: DeLorey
keywords: Exercise; nitric oxide; sympathetic nervous system; sympatholysis; vascular conductance