ORIGINAL PAPER Effect of tetrahydrobiopterin and exercise training on endothelium-dependent vasorelaxation in SHR François Guerrero & Sanéo Thioub & Christelle Goanvec & Sigrid Theunissen & Annie Feray & Costantino Balestra & Jacques Mansourati Received: 31 January 2012 / Accepted: 5 September 2012 # University of Navarra 2012 Abstract We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH 4 -dependent mechanism. Male spontaneously hypertensive rats (SHR, n 0 20) and Wistar-Kyoto rats (WKY, n 0 20) were trained (Tr) for 9 weeks on a treadmill and compared to age-matched sedentary animals (Sed). Endothelium-dependent vasorelaxation (EDV) was assessed with acetylcholine by measuring isometric tension in rings of femoral artery precontracted with 10 -5 M phenylephrine. EDV was impaired in SHR- Sed as compared to WKY-Sed (p 0 0.02). Training alone improved EDV in both WKY (p 0 0.01) and SHR (p 0 0.0001). Moreover, EDV was not different in trained SHR than in trained WKY (p 0 0.934). Pre- treatment of rings with L-NAME (50 μM) cancelled the difference in ACh-induced relaxation between all groups, suggesting that NO pathway is involved in these differences. The presence of 10 -5 M BH 4 in the organ bath significantly improved EDV for sedentary SHR (p 0 0.030) but not WKY group (p 0 0.815). Ex- ercise training turned the beneficial effect of BH 4 on SHR to impairment of ACh-induced vasorelaxation in both SHR-Tr (p 0 0.01) and WKY-Tr groups (p 0 0.04). These results suggest that beneficial effect of exercise training on endothelial function is due partly to a BH 4 - dependent mechanism in established hypertension. Keywords Hypertension . Rat . Exercise . Endothelial dysfunction . Nitric oxide . Tetrahydrobiopterin Introduction Impaired endothelial function is associated with a number of pathological conditions, including cigarette smoking, dyslipidemia, obesity, diabetes mellitus, and hypertension [1]. It is considered as the first step towards atherosclerosis and an independent cardiovas- cular risk factor [33]. Numerous interventions that J Physiol Biochem DOI 10.1007/s13105-012-0210-y F. Guerrero (*) : S. Thioub : C. Goanvec : A. Feray : J. Mansourati European University of Britany, University of Brest, EA4324 ORPHY, 6 avenue Le Gorgeu, CS 93837, 29238 Brest, France e-mail: francois.guerrero@univ-brest.fr F. Guerrero : A. Feray Faculty of Sport and Physical Education, European University of Britany, University of Brest, 20 avenue le Gorgeu, CS 93837, 29238 Brest, France C. Goanvec Faculty of Sciences and Techniques, European University of Britany, University of Brest, 6 avenue le Gorgeu, CS 93837, 29238 Brest, France S. Theunissen : C. Balestra Haute Ecole Paul Henri Spaak, Environmental and Occupational Physiology Lab, Brussels, Belgium J. Mansourati Department of Cardiology, University Hospital of Brest, Brest, France