title: Changes in guanylate cyclase activity in arteriolar smooth muscle cells and hemodynamics after ischemia-reperfusion in rats.
abstract: Participation of nitric oxide (NO) and hydroxyl radicals in the pathogenesis of hemodynamic alterations after postischemic recirculation were examined by measuring cerebral blood flow (CBF) and estimating guanylate cyclase activities in arteriolar smooth muscle cells using a reversible 2-h thread occlusion model in rats and an electron microhistochemical technique. In the reversible 2-h ischemia model, guanylate cyclase activity in the arteriolar smooth muscle cells increased at the peak of hyperemia and decreased during postischemic hypoperfusion. Administration of N(omega)-nitro-l-arginine (L-NNA), a NO synthase inhibitor, in this model decreased infarct volume and completely inhibited both hyperemia and guanylate cyclase activation at hyperemia. Administration of 1,2-bis(nicotinamido)-propane (AVS), a free radical scavenger, affected neither CBF nor guanylate cyclase activity during hyperemia despite a significant reduction in infarct volume. Administration of L-NNA and AVS significantly suppressed the decrease in CBF during postischemic hypoperfusion and the effect of AVS was greater than that of L-NNA. Although continuous infusion of sodium nitroprusside (SNP) following postischemic hypoperfusion in the reversible 2-h ischemia rats without treatment with L-NNA and AVS did not alter either CBF or guanylate cyclase activity, it significantly elevated both CBF and guanylate cyclase activities in rats administered L-NNA and AVS. The responses of CBF and guanylate cyclase to SNP were also greater in AVS- than L-NNA-treated rats. These results suggest that a physiological vasodilative mechanism is involved in the induction of postischemic hyperemia through the NO-guanylate cyclase pathway in arteriolar smooth muscle cells. Both NO-related and non-related radicals are involved in the pathogenesis of postischemic delayed hypoperfusion through the loss of arteriolar smooth muscle relaxation capability.
authors.affiliation: Department of Neurological Surgery, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, 791-0295, Japan. hisaki@m.ehime-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: H
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Y
authors.initials: Y
authors.lastname: Kumon
authors.forename: S
authors.initials: S
authors.lastname: Sakaki
authors.forename: S
authors.initials: S
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Sakanaka
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009536:Niacinamide; D009569:Nitric Oxide; D012965:Sodium Chloride; D006162:Guanylate Cyclase; C042625:nicaraven