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ArticleTitle | Inhibition of Inducible Nitric Oxide Synthase Attenuates Interleukin-1β Induced Vascular Hyporeactivity in the Rabbit |
AuthorList | Toru Shimizu, Atsuhiro Sakamoto and Ryo Ogawa |
Affiliation | Department of Anesthesiology, Nippon Medical School |
Language | EN |
Volume | 69 |
Issue | 2 |
Year | 2002 |
Page | 149-153 |
Received | July 19, 2001 |
Accepted | August 28, 2001 |
Keywords | nitric oxide, interluekin-1β, vascular reactivity, L-canavanine |
Abstract | Inhibition of nitric oxide (NO) synthesis has been indicated to improve vasopressor-responsiveness and to increase blood pressure in most septic models. However, numerous adverse effects of non-selective NO synthase (NOS) inhibition have been reported, and the effect of NOS inhibition on vascular responsiveness to vasodilators has not been well studied. Using an isometric tension measurement system of vascular rings, we evaluated the effects of an inducible NOS (iNOS) inhibitor, L-canavanine (L-CAN) and a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on interleukin-1β(IL-1β) -induced vascular hyporeactivity in the four different rabbit arteries. Pretreatment of IL-1βinhibited phenylephrine (Phe) -induced vascular constriction in the carotid artery (CA, 49% of control), pulmonary artery (PA, 66%), femoral artery (FA, 71%) and in the renal artery (RA, 83%). A combination of NOS inhibitors attenuated the vascular hyporeactivity to Phe in all arteries. Pretreatment of IL-1βalso inhibited acetylcholine (Ach) -induced vascular relaxation in FA, RA and CA. In PA, the rings were inversely constricted after Ach administration. The combination of IL-1βwith L-CAN, but not with L-NAME, attenuated the Ach-induced vasorelaxation to the control level in all arteries. These data suggest that the selective inhibition of iNOS attenuates the direct endothelial damage induced by IL-1βin vitro. |
Correspondence to | Toru Shimizu, Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan hopno-1@nms.ac.jp |
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