Vascular smooth muscle nitric oxide synthase anomalies in Dahl/Rapp salt-sensitive rats.
Salt-sensitive hypertension in the Dahl/Rapp rat (S strain) is prevented by L-arginine. Based on the observations that dexamethasone prevented the antihypertensive effect of L-arginine in these animals and the suggestion that a locus in or near an inducible nitric oxide synthase (NOS) gene on chromosome 10 cosegregated with hypertension in some F2 crosses that utilized the S rat, the present study explored the hypothesis that the vascular smooth muscle isoform of inducible NOS (NOS2) was abnormal in S rats. Primary cultures of aortic smooth muscle cells from S rats demonstrated impaired inducible NO production, which improved with increased L-arginine in the medium. Sequence analysis identified a single T-->C transversion that produced an amino acid substitution (S714P) between the FAD and FMN binding sites and a restriction fragment length polymorphism. This restriction fragment length polymorphism was present only in S rats. The mutation of NOS2 and the role of this enzyme in the pathogenesis of salt-sensitive hypertension in the Dahl/Rapp rat require further investigation.
Chen
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PY
Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, and Department of Veterans Affairs Medical Center, 35294-0007, USA.
Gladish
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RD
Sanders
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D017931:DNA Primers; D005838:Genotype; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009154:Mutation; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000009:adverse effects
D017931:DNA Primers; D012333:RNA, Messenger; D012982:Sodium, Dietary; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat