Attenuated inhibition of adrenergic contraction by nitric oxide in injured guinea pig femoral artery.

The present study aimed to examine the altered modulation of adrenergic contraction by nitric oxide and sensory neuropeptides in balloon-injured muscular artery. A guinea pig femoral artery (GPFA) was injured by a newly developed silastic microballoon catheter. The contralateral GPFA served as the control. The studied GPFAs consisted of six groups; control (C) and injured (I) GPFA, isolated at 0 days, and 2 and 8 weeks after injury (C0, I0, C2, I2, C8, and I8). Isometric tension was measured in the presence of indomethacin (10(-5) M), to exclude effects of cyclooxygenase-generated eicosanoids. Endothelial removal with the catheter was confirmed by histological examination. In each group, except for 10, NG-nitro-I-arginine methyl ester (L-NAME, 10(-6) M) induced significant augmentation of perivascular nerve stimulation (PNS)-evoked adrenergic contraction, which was blocked by L-arginine (3 x 10(-4) M). The degree of L-NAME augmentation in I8 was significantly smaller than that in C8 and I2. Capsaicin (10(-6) M) did not significantly affect PNS-contraction in any group, indicating that there was no sensory neuropeptide involvement in this contraction. In I8, acetylcholine (10(-6) M)-induced relaxation after noradrenaline (10(-5) M)-precontraction was significantly smaller than that seen in the other groups, except for I0, which was lacking in acetylcholine-induced relaxation. Histologically, injured GPFAs showed progressive intimal thickening. The present findings thus showed attenuated nitric oxide-mediated inhibition of adrenergic contraction, accompanying intimal thickening, in balloon-injured muscular artery, 8 weeks after injury.