Endotoxin Decreases the Contractile Responses of the Porcine Basilar Artery to Vasoactive Substances

The effects of endotoxin (lipopolysaccharide; LPS) on the reactivity of isolated porcine basilar artery were examined using in vitro tissue bath techniques. The active muscle tone of the basilar arterial rings with or without endothelial cells induced by U46619 (1 microM) reached a plateau in 15 min, which was stable for the first hour and gradually decreased during the next 5 h. This time-dependent decrease in tone was significantly potentiated in the presence of LPS (20 micrograms/ml). The potentiation by LPS was blocked by Nw-nitro-L-arginine (L-NNA; 60 microM), methylene blue (10 microM), and dexamethasone (1 microM) but not by hemoglobin (1 microM). The effect of L-NNA was readily reversed by L-arginine but not by D-arginine. Furthermore, the contractile responses of porcine basilar arterial rings with or without intact endothelium to U46619 and KCl were decreased following incubation with LPS (20 micrograms/ml) for 4 h. Similar hyporeactivity was observed in cold storage-denervated cerebral arteries incubated with LPS for 4 h. This decrease in contractile responses in LPS-treated rings was reversed by 60 microM L-NNA and 1 microM dexamethasone. These results indicate that LPS treatment renders the porcine basilar arteries hyporesponsive to vasoconstrictors. Since effects of LPS were not modified by the presence of endothelial cells and perivascular neurons, the alteration in cerebral arterial reactivity may be due in part to an enhanced formation of nitric oxide from L-arginine in the vascular smooth muscle cells.