title: Impaired flow-mediated vasodilation in vivo and reduced shear-induced platelet reactivity in vitro in response to nitric oxide in prothrombotic, stroke-prone spontaneously hypertensive rats.
abstract: Previous investigations using an He-Ne laser-induced thrombosis method have shown that stroke-prone spontaneously hypertensive rats (SHRSP) have an enhanced thrombotic tendency in vivo compared to normotensive, Wistar Kyoto rats (WKY). In addition, studies in the presence of acetylcholine have suggested the presence of endothelial dysfunction in SHRSP. In contrast, shear-induced platelet reactivity in vitro appeared to be depressed in SHRSP. The aim of the present study was to investigate endothelial function in SHRSP using a new physiological in vivo model, and to determine the response of platelets to nitric oxide (NO) in non-anticoagulated blood using a shear-induced platelet function in vitro method (haemostatometry). Endothelial function was estimated by measuring flow-mediated vasodilation (FMV) of the femoral artery. Vessels were exposed and blood flow was arrested using a silicone-coated arterial clamp. Vasodilation was measured by computer-assisted image analysis 3 min after release of stasis. Arterial vasodilation was observed in the femoral artery of WKY, but not in SHRSP. Vasodilation was seen in both WKY and SHRSP; however, in response to the NO donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC 5). In contrast, 100 microM NOC 5 did not affect platelet reactivity in SHRSP. The NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, sodium salt (carboxy-PTIO) and the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, hydrochloride (L-NAME), did not affect shear-induced platelet reactivity. NOC 5 at 10 microM (final concentration) inhibited shear-induced platelet reactivity in WKY. These results confirm the presence of endothelial dysfunction in SHRSP and indicate that platelets are non-responsive to NO in this hypertensive model. The data suggest that defective endothelial reactions or disturbed thrombogenic mechanisms outweigh the platelet hyporeactivity and contribute to the prothrombotic status in SHRSP.
authors.affiliation: Laboratory of Physiology, Faculty of Nutrition and High Technology Research Centre, Kobe Gakuin University, Kobe, Japan. tomomi_oishi@mbk.nifty.com
authors.forename: Tomomi
authors.initials: T
authors.lastname: Taka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ohta
authors.forename: Junji
authors.initials: J
authors.lastname: Seki
authors.forename: John C
authors.initials: JC
authors.lastname: Giddings
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D010477:Perfusion; D015539:Platelet Activation / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow; D015424:Reperfusion; D020521:Stroke / Q000209:etiology; D019851:Thrombophilia / Q000209:etiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D009569:Nitric Oxide