Nitric oxide in the potassium-induced response of the rat middle cerebral artery: a possible permissive role

In the middle cerebral artery (MCA), the presence of nitric oxide (NO) is responsible for maintaining a more dilated state than in its absence during increases in extracellular K+ and osmolality. The purpose of the present study was to determine whether the involvement of NO was due to (a) a direct effect of the K+/osmolality (K-hyper) on the endothelium or (b) a 'permissive' role of NO. MCAs (approximately 210 mum o.d.) were isolated, cannulated with glass micropipettes, and pressurized to 85 mmHg. When K+ (KCl) in the extraluminal bath was increased to 21 mM, the diameter increased by 15-20% with the magnitude of dilation diminishing with further increases in K-hyper. The addition of N-G-nitro-L-arginine methyl ester (L-NAME, 10(-5) mM), an inhibitor of nitric oxide synthase, had no significant effect on dilations at lower K-hyper concentrations but constricted the arteries relative to the control at 51, 66, and 81 mM K-hyper In the presence of L-NAME, the addition of an exogenous NO donor, S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) M) or an analog of cCMP, 8-bromo-cGMP (6X10(-5) M), tended to restore the response of K-hyper to near the original response. We conclude that the basal release of NO from the endothelium plays a permissive role in the K-hyper-induced response. (C) 2001 Elsevier Science B.V. All rights reserved.