title: Pulsatile flow enhances endothelium-derived nitric oxide release in the peripheral vasculature.
abstract: The effects of pulsatility in blood flow on endothelium-derived nitric oxide (EDNO) release in the peripheral vasculature were investigated. The basal and flow-stimulated EDNO release were compared between pulsatile and nonpulsatile systemic flows before and after the administration of NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Peripheral vascular resistance (PVR) was significantly lower in pulsatile flow than in nonpulsatile flow, but this difference disappeared after L-NMMA. The percent increase in PVR by L-NMMA was significantly larger in pulsatile flow. In reactive hyperemia in the hindlimb, the peak flow did not differ; however, both the repayment flow and the duration were significantly larger in pulsatile flow. Percent changes of these parameters by L-NMMA were significantly larger in pulsatile flow. These data indicated that pulsatility significantly enhances the basal and flow-stimulated EDNO release in the peripheral vasculature under in vivo conditions. We also studied the involvement of the Ca(2+)-dependent and Ca(2+)-independent pathways in flow-induced vasodilation using calmodulin inhibitor calmidazolium and tyrosine kinase inhibitor erbstatin A. PVR was significantly elevated by erbstatin A but not by calmidazolium, suggesting that flow-induced vasodilation was largely caused by tyrosine kinase inhibitor-sensitive activation of NO synthase.
authors.affiliation: Division of Cardiovascular Surgery, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.forename: R
authors.initials: R
authors.lastname: Tominaga
authors.forename: I
authors.initials: I
authors.lastname: Nagano
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: H
authors.initials: H
authors.lastname: Yasui
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000201:enzymology; D006614:Hindlimb / Q000098:blood supply; D006873:Hydroquinones / Q000494:pharmacology; D006940:Hyperemia / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011673:Pulsatile Flow / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D002395:Catecholamines; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007093:Imidazoles; D009566:Nitrates; D009573:Nitrites; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C031938:calmidazolium; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C048212:erbstatin