title: Impaired effect of salt loading on nitric oxide-mediated relaxation in aortas from stroke-prone spontaneously hypertensive rats.
abstract: 1. The present study was designed to characterize the effects of salt on vasorelaxation via the nitric oxide (NO)/cGMP pathway in stroke-prone spontaneously hypertensive rats (SHRSP), which are highly salt sensitive. 2. Male 8-week-old SHRSP were given 1% NaCl solution as drinking water for 4 weeks, whereas control animals were given water only. 3. In aortic rings from salt-loaded SHRSP, relaxations in response to acetylcholine and sodium nitroprusside were significantly impaired compared with those in the control. In the presence of zaprinast, a cGMP-specific cyclic nucleotide phosphodiesterase (PDE)-5 inhibitor, the cGMP levels induced by these drugs were significantly reduced by salt loading, but remained unchanged in the absence of zaprinast. The protein levels of endothelial NO synthase, soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG) remained unchanged with salt loading, but those of PDE-5 decreased significantly and those of phosphorylated PKG tended to decrease, although the change was not statistically significant. Salt loading significantly impaired the relaxation in response to 8-bromo-cGMP. 4. These results indicate that, in aortas from SHRSP, salt loading causes impairment of relaxation in response to NO, which may be due to a decrease in cGMP production by sGC and impairment of the relaxation pathway downstream of cGMP, which, in turn, probably causes a decrease in PKG activity. Reduced PDE-5 protein expression may act, in part, as a compensatory response to impairment of cGMP-mediated relaxation.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. skagota@mukogawa-u.ac.jp
authors.forename: Satomi
authors.initials: S
authors.lastname: Kagota
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Namie
authors.initials: N
authors.lastname: Nejime
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Masaru
authors.initials: M
authors.lastname: Kunitomo
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shinozuka
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006162:Guanylate Cyclase / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009566:Nitrates; D017673:Sodium Chloride, Dietary; D017392:Thiobarbituric Acid Reactive Substances; D013873:Thionucleotides; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D000244:Adenosine Diphosphate; D052250:Nitric Oxide Synthase Type III; D017869:Cyclic GMP-Dependent Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP; D000109:Acetylcholine