Evidence for inducible nitric oxide synthase in spontaneously hypertensive rats.
This study investigates the mechanism of the production of nitric oxide (NO) caused by lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats. The injection of LPS (5 mg/ kg, i.v.) caused a mild hypotension in WKY rats, while it induced a more severe hypotensive effect in SHR. The basal level of plasma nitrite was slightly higher in SHR than in WKY rats. At 3 h after injection of LPS, the increment in plasma nitrite was more significant in SHR. Prior to the treatment of rats with LPS, the plasma level of tumor necrosis factor-alpha (TNF alpha) was also higher in SHR than in WKY rats, and LPS induced a more significant increase of TNF alpha level (at 1 h) in SHR. In rats treated with LPS, acetylcholine-induced relaxation was significantly impaired in thoracic aortic rings obtained from WKY rats, but not in those from SHR. By contrast, L-arginine (1 mM) did not cause any relaxations in rings without the endothelium obtained from WKY rats while it slightly relaxed those from SHR, and this difference was further augmented by treatment of rats with LPS for 3 h. In addition, the basal cGMP level was higher in SHR, which was inhibited by aminoguanidine (AG, 1 mM). The treatment of rats with LPS further increased the formation of cGMP in both strains and this increment was greater in SHR than in WKY rats, which was also attenuated by AG to a similar level between both strains. Interestingly, an expression of inducible NO synthase (NOS II) protein was only observed in SHR, and further enhanced by treated rats with LPS. We conclude that an increased production of NO in SHR, which was further enhanced by LPS, is attributed to a basal expression of NOS II.
Wu
C C
CC
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Repbulic of China.
Hong
H J
HJ
Chou
T C
TC
Ding
Y A
YA
Yen
M H
MH
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004790:Enzyme Induction; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006146:Guanidines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000109:Acetylcholine; C004479:pimagedine; D015056:1-Methyl-3-isobutylxanthine