The L-arginine inhibition of rat middle cerebral artery contractile responses is mediated by inducible nitric oxide synthase.
1. The effect of L-arginine (L-Arg), the nitric oxide synthase (NOS) substrate, on the responses to prostaglandin F2alpha (PGF2alpha, 10 microM) and K+ (120 mM) in rat middle cerebral artery (MCA) segments was analysed. 2. PGF2alpha induced a stable contraction of 0.35+/-0.06 mN mm(-1); the subsequent addition of bradykinin (BK, 1 microM) produced a relaxation of 42+/-9% of the PGF2alpha-induced tone. K+ induced a response consisting of a rapid basal tone increase (1.42+/-0.16 mN mm(-1)) followed by a decrease to a stable phase (1.24+/-0.15 mN mm(-1)). 3. L-Arg (0.1 mM), but not D-Arg, decreased the basal tone and reduced the contraction to PGF2alpha in segments with and without endothelium. The contractile response to K+ was also reduced and not maintained in the presence of L-Arg. 4. The inhibitory effect of L-Arg on the PGF2alpha- and K+-induced contractions was completely reversed by the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA, 0.1 mM). 5. Pre-incubation of segments with dexamethasone (1 microM), to inhibit inducible NOS (iNOS), or with the antibiotic polymyxin B (10 microg ml(-1)) reduced the L-Arg inhibition, whereas it was increased by lipopolysaccharide (LPS, 100 ng ml(-1)), an inductor of iNOS. L-NMMA antagonized the effects of dexamethasone and LPS. 6. The present results suggest that L-Arg inhibition of the PGF2alpha- and K+-induced contractions in rat MCA is the result of NO synthesis by iNOS stimulation.
Alonso
M J
MJ
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Rodríguez-Martínez
M A
MA
Martínez-Orgado
J
J
Marín
J
J
Salaices
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011188:Potassium / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D008070:Lipopolysaccharides; D003907:Dexamethasone; D001120:Arginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D011188:Potassium