Promotion of nitric oxide formation by heparin in cultured aortic endothelial cells from spontaneously hypertensive rats.
1. The present study examined the effect of heparin on nitric oxide (NO) formation and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in cultured aortic endothelial cells (EC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Bradykinin (BK), adenosine diphosphate (ADP), Ca2+ ionophore A23187 (Io) and endothelin-3 (ET-3) stimulated the production of NO and cGMP. No significant difference was observed in both NO and cGMP production in EC between WKY and SHR. 3. Heparin enhanced BK-, ADP-, Io- and ET-3-stimulated NO and cGMP production. These enhancements by heparin in EC were significantly greater in SHR than in WKY. 4. Both NO formation and cGMP production stimulated by the agonists and/or heparin were blocked in the presence of NG-monomethyl-L-arginine (LNMMA, 10(-5) mol/L). 5. Increased sulphur level was observed on heparin-treated SHR EC surface compared with that on control SHR EC or on heparin-treated WKY EC surface. 6. These results suggest that heparin promotes agonist-induced NO-cGMP response in cultured EC from SHR.
Minami
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Yokokawa
K
K
Kohno
M
M
Ikeda
M
M
Horio
T
T
Kano
H
H
Hanehira
T
T
Yasunari
K
K
Takeda
T
T
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D006493:Heparin; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP