title: The production of vasoconstriction-induced residual NO modulates perfusion pressure in rat mesenteric vascular bed.
abstract: In the presence of nitric oxide synthase (NOS) inhibitors, the contribution of residual NO to endothelium-dependent relaxation induced by chemical agonists acetylcholine and bradykinin has been documented in resistance vessels. However, the contribution of residual NO to the vasodilatation in response to pressure and fluid shear stress is not well understood. In this study, to demonstrate the activity of residual NO, we applied a NO scavenger, hydroxocobalamin (HCX), on the phenylephrine-induced increase in perfusion pressure in the presence of NOS inhibitors, Nω-nitro-L-arginine (L-NA) or Nω-nitro-L-arginine methyl ester (L-NAME) in the rat perfused mesenteric bed. The perfusion pressure was increased by phenylephrine (1-2 µM), an α1-adrenoceptor agonist. This increase was augmented by the addition of L-NA or L-NAME. In the presence of any NOS inhibitors, the application of hydroxocobalamin (100 µM) further increased the perfusion pressure. The removal of endothelium by saponin (50 mg/L) and the use of a non-selective protein kinase inhibitor, staurosporine (5 nM), and a tyrosine kinase inhibitor, erbstatin A (30 µM), but not a calmodulin inhibitor, calmidazolium (0.5 µM), inhibited the additional pressor responses induced by L-NA or L-NAME and a combination of either of them with hydroxocobalamine. These findings show that there could be a NOS inhibitor-resistant residual NO production in response to pressure in the rat mesenteric vascular bed. This residual NO production may be associated with the activation of tyrosine kinase and protein kinases, but not calmodulin. Finally, this pressure-induced residual NO exerts a modulatory role against vasoconstriction induced by phenylephrine.
authors.affiliation: Department of Pharmacology, Çukurova University, Medical School, Adana, Turkey asecilmis@cu.edu.tr.
authors.forename: M A
authors.initials: MA
authors.lastname: Seçilmiş
authors.affiliation: Department of Pharmacology, Çukurova University, Medical School, Adana, Turkey.
authors.forename: Ö Y
authors.initials: ÖY
authors.lastname: Özü
authors.affiliation: Department of Pharmacology, Çukurova University, Medical School, Adana, Turkey.
authors.forename: O E
authors.initials: OE
authors.lastname: Kıroğlu
authors.affiliation: Department of Pharmacology, Çukurova University, Medical School, Adana, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Şingirik
authors.affiliation: Department of Pharmacology, Medical Faculty Mersin University, Campus Yenişehir, Mersin, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Büyükafşar
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006873:Hydroquinones / Q000494:pharmacology; D006879:Hydroxocobalamin / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000494:pharmacology; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007093:Imidazoles; D014803:Vitamin B Complex; D010656:Phenylephrine; D009569:Nitric Oxide; C031938:calmidazolium; D019311:Staurosporine; D006879:Hydroxocobalamin; D019331:NG-Nitroarginine Methyl Ester; C048212:erbstatin
keywords: mesenteric artery; perfusion pressure; residual NO