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 F-2 alpha (PGF(2 alpha), 10 mu M) and K+ (120 mM) in rat middle cerebral artery (MCA) segments was analysed. 2 PGF(2 alpha) induced a stable contraction of 0.35 +/- 0.06 mN mm(-1); the subsequent addition of bradykinin (BK, 1 mu M) produced a relaxation of 42 +/- 9% of the PGF(2 alpha)-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 PGF(2 alpha) 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 PGF(2 alpha)- and K+-induced contractions was completely reversed by the NOS inhibitor, N-G-monomethyl-L-arginine (L-NMMA, 0.1 mM). 5 Pre-incubation of segments with dexamethasone (1 mu M), to inhibit inducible NOS (iNOS), or with the antibiotic polymyxin B (10 mu g 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 PGF(2 alpha)- and K+-induced contractions in rat MCA is the result of NO synthesis by iNOS stimulation.