Acute tetrahydrobiopterin supplementation attenuates sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of healthy rats

Tetrahydrobiopterin ( BH 4 ) is an essential cofactor for the production of nitric oxide ( NO ) and supplementation with BH 4 improves NO ‐dependent vasodilation. NO also reduces sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle. Thus, we hypothesized that supplementation with BH 4 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 BH 4 supplementation (20 mg·kg −1 + 10 mg·kg −1 ·h −1 , IA ) conditions. BH 4 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%; BH 4 : 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%; BH 4 : 2 Hz: −6 ± 6% FVC ; 5 Hz: −16 ± 10%) and 60% MCF (Control: 2 Hz: −7 ± 3% FVC ; 5 Hz: −16 ± 6% FVC ; BH 4 : 2 Hz: −2 ± 3% FVC ; 5 Hz: −11 ± 6% FVC ). These data are consistent with our hypothesis that acute BH 4 supplementation decreases sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle.