Interleukin-1beta causes different levels of nitric oxide-mediated depression of contractility in different positions of rat thoracic aorta.

Interleukin-1beta (IL-1beta) can be synthesized by macrophages, endothelial cells and vascular smooth muscle cells when stimulated by bacterial lipopolysaccharide (endotoxin) during septic shock. The IL-1beta levels in the blood vessel wall are also elevated in atherosclerosis. IL-1beta can cause induction of inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle cells and produce vasorelaxation, hypotension and ultimately tissue damage. We studied the depressions of vascular smooth muscle contractions at 3 hours after exposure to IL-1beta in different positions of rat thoracic aorta. The data show that the aortic rings from the cranial end of rat thoracic aorta had little response to IL-1beta (0.5 and 1.0 ng/ml) while those from the caudal end of thoracic aorta had larger depressant response. S-methylisothiourea sulfate (SMT), an iNOS inhibitor, completely blocked the depression of contraction caused by IL-1beta in intact aortic rings. If the endothelium was removed from the aortic rings before exposure to IL-1beta, all rings from different parts of the thoracic aorta showed an equal amount of vasodepression. Thus, the difference in the depressant response of IL-1beta in different portions of thoracic aorta is endothelium-dependent and involves induction of NOS.