Inhibition of inducible nitric oxide synthase attenuates interleukin-1 beta induced vascular hyporeactivity in the rabbit.
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-1 beta (IL-1 beta)-induced vascular hyporeactivity in the four different rabbit arteries. Pretreatment of IL-1 beta inhibited 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-1 beta also 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-1 beta with 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-1 beta in vitro.
Shimizu
Toru
T
Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. hopno-1@nms.ac.jp
Sakamoto
Atsuhiro
A
Ogawa
Ryo
R
D000818:Animals; D002172:Canavanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014666:Vasomotor System / Q000187:drug effects*
D006834:Hydrazines; D007375:Interleukin-1; C410363:canavanine phenylhydrazide; D010656:Phenylephrine; D002172:Canavanine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester