Characteristics of contractile responses of aorta to norepinephrine in db/db mice.

In the isolated mouse aorta with endothelium, although norepinephrine (NE) showed only a slight increase in tension in control mice, the NE-induced dose-dependent contraction was markedly increased in spontaneously diabetic mice. NE-induced contractile responses were significantly enhanced by pretreatment with 10(-4) NG-monomethyl-L-arginine (L-NMMA), 5 micrograms/ml lysophosphatidylcholine (LPC), and the combined treatment with L-NMMA and LPC. When the aortic ring was precontracted with 3 x 10(-6) M PGF2 alpha, NE (10(-8) to 3 x 10(-5) M) caused dose-dependent relaxation. The NE-induced relaxation was significantly inhibited by 10(-4) L-NMMA or 5 micrograms/ml LPC in the normal mice. These results suggest that insensitivity of the mouse aorta to NE is due to the release of nitric oxide from the endothelium, and that an increased contraction induced by NE in spontaneously diabetic mice is due to an impairment of the endothelium.