Reduced expressions of inducible nitric oxide synthase and cyclooxygenase-2 in vascular smooth muscle cells of stroke-prone spontaneously hypertensive rats.
Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are expressed in vascular smooth muscle cells stimulated with interleukin-1beta (IL-1beta), resulting in the production of nitric oxide (NO) and prostaglandins (PGs) such as PGI2. The iNOS and COX-2 proteins and their mRNA expressions in cultured vascular smooth muscle cells isolated from 6-7 week-old stroke-prone spontaneously hypertensive rats (SHRSP) were compared with those in the cells isolated from age-matched normotensive Wistar Kyoto rats (WKY). The IL-1beta-induced NO production and iNOS expression in vascular smooth muscle cells of SHRSP were significantly lower than those in cells of WKY. Similarly, PGI2 production and COX-2 expression were significantly lower in vascular smooth muscle cells of SHRSP than WKY, whereas there was no difference in the COX-1 expression. There were no significant differences in iNOS and COX-2 mRNA expressions between the two strains, suggesting that these protein expression may be reduced at the post-transcriptional level in cells of SHRSP. These results further suggest that the reduction of iNOS and COX-2 expressions in vascular smooth muscle cells may have relevance to the pathophysiology in SHRSP.
Hirafuji
Masahiko
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan. hirafuji@hoku-iryo-u.ac.jp
Tsunoda
Marito
M
Machida
Takuji
T
Hamaue
Naoya
N
Endo
Toru
T
Miyamoto
Atsushi
A
Minami
Masaru
M
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D011464:Epoprostenol / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology*; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007375:Interleukin-1; D007527:Isoenzymes; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases