title: Impaired nitric oxide- and prostaglandin-mediated responses to flow in resistance arteries of hypertensive rats.
abstract: In human and experimental hypertension, flow (shear stress)-induced dilation in large arteries is attenuated and resistant to nitric oxide blockade. We tested the hypothesis that a defect in nitric oxide-and/or prostaglandin-dependent flow-induced dilation might occur in mesenteric resistance arteries from spontaneously hypertensive rats (SHR). We measured resistance mesenteric artery diameter in situ by intravital microscopy and simultaneously measured mesenteric arterial pressure in a collateral artery. The flow-diameter-pressure relationship was established in normotensive Wistar-Kyoto rats (WKY) and in SHR under control conditions and after endothelium removal, inhibition of nitric oxide synthesis with N omega-nitro-L-arginine methyl ester (10 micromol/L), or inhibition of prostaglandin synthesis with indomethacin (10 micromol/L). Production of prostaglandins was determined in the perfusate. Endothelium removal decreased artery diameter by 14 +/- 1.6% in WKY and 5 +/- 0.5% (P<.01 versus WKY) in SHR at a flow rate of 400 microL/min. In WKY, N omega-nitro-L-arginine methyl ester and indomethacin decreased resistance artery diameter by 12 +/- 3% (P<.001) and 5 +/- 2% (P<.01), respectively, at a flow rate of 400 microL/min; neither substance had any significant effect in SHR. In both strains, flow induced the production of 6-keto-prostaglandin F1alpha, the metabolite of prostacyclin; prostaglandin F2alpha; and thromboxane B2, the stable metabolite of thromboxane A2. Production of 6-keto-prostaglandin F1alpha and prostaglandin F2alpha was significantly lower in SHR than WKY, and TxB2 production was significantly higher in SHR than WKY. The present findings suggest that in SHR mesenteric resistance arteries, dilation in response to increases in flow was resistant to nitric oxide and prostaglandin synthesis blockade. A modification of the ratio of vasodilator to vasoconstrictor prostaglandins might be at least partly responsible for the decreased dilator response to flow in SHR.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U141, IFR Circulation Lariboisière, Université Paris VII, France.
authors.forename: K
authors.initials: K
authors.lastname: Matrougui
authors.forename: J
authors.initials: J
authors.lastname: Maclouf
authors.forename: B I
authors.initials: BI
authors.lastname: Lévy
authors.forename: D
authors.initials: D
authors.lastname: Henrion
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000502:physiology; D013929:Thromboxane B2 / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D011460:Prostaglandins F; D009569:Nitric Oxide; D013929:Thromboxane B2; D015237:Dinoprost; C100006:prostaglandin F1