title: Effect of tetrahydrobiopterin and exercise training on endothelium-dependent vasorelaxation in SHR.
abstract: We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH4-dependent mechanism. Male spontaneously hypertensive rats (SHR, n = 20) and Wistar-Kyoto rats (WKY, n = 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 = 0.02). Training alone improved EDV in both WKY (p = 0.01) and SHR (p = 0.0001). Moreover, EDV was not different in trained SHR than in trained WKY (p = 0.934). Pretreatment 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 BH4 in the organ bath significantly improved EDV for sedentary SHR (p = 0.030) but not WKY group (p = 0.815). Exercise training turned the beneficial effect of BH4 on SHR to impairment of ACh-induced vasorelaxation in both SHR-Tr (p = 0.01) and WKY-Tr groups (p = 0.04). These results suggest that beneficial effect of exercise training on endothelial function is due partly to a BH4-dependent mechanism in established hypertension.
authors.affiliation: European University of Britany, University of Brest, EA4324 ORPHY, 6 avenue Le Gorgeu, CS 93837, 29238, Brest, France, francois.guerrero@univ-brest.fr.
authors.forename: François
authors.initials: F
authors.lastname: Guerrero
authors.forename: Sanéo
authors.initials: S
authors.lastname: Thioub
authors.forename: Christelle
authors.initials: C
authors.lastname: Goanvec
authors.forename: Sigrid
authors.initials: S
authors.lastname: Theunissen
authors.forename: Annie
authors.initials: A
authors.lastname: Feray
authors.forename: Costantino
authors.initials: C
authors.lastname: Balestra
authors.forename: Jacques
authors.initials: J
authors.lastname: Mansourati
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010805:Physical Conditioning, Animal; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001708:Biopterins; C003402:sapropterin