A nitric oxide synthesis inhibitor decreased prostaglandin production in rat mesenteric vasculature.
Endothelial cells synthesize and release nitric oxide (NO) and prostacyclin (PGI2) which are involved in the regulation of vascular tone and blood pressure. Our objective was to evaluate the effects of inhibiting NO synthesis on vascular prostaglandin (PG) and cyclic nucleotide production, as well as the pressor response to norepinephrine (NE). Isolated mesenteric arterial beds were perfused with Krebs-Henseleit solution containing 100 microM NG-monomethyl-L-arginine (L-NMMA), 100 microM L-arginine (LA), or vehicle. After a 30 min equilibration 0.1, 0.5, 1, or 5 microM NE was infused into the superior mesenteric artery and the perfusion pressure was monitored. The basal perfusion pressure did not differ significantly between groups. The pressure-response curve was shifted to the right in the L-NMMA group vs. the LA and control groups. Perfusion was similarly performed with a Krebs-Henseleit solution containing 100 microM L-NMMA, LA, D-arginine, or vehicle. Perfusates were collected before and after NE infusion for the measurement of PGE2, 6-keto-PGF1 alpha, TxB2, cAMP, and cGMP. In the L-NMMA group the release of PGE2 and 6-keto-PGF1 alpha was decreased, and the release of cGMP was prevented. Production of cAMP did not differ between the four groups before NE infusion, and NE increased cAMP release in the L-NMMA group and controls. The results indicate that inhibition of NO synthesis by L-NMMA enhanced the pressor response to NE, possibly mediated by the decreased cGMP and PGI2 production in resistance vessels.
Soma
M
M
Second Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Izumi
Y
Y
Watanabe
Y
Y
Kanmatsuse
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015777:Eicosanoids / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine
D015777:Eicosanoids; D004791:Enzyme Inhibitors; D009712:Nucleotides, Cyclic; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine