TY - JOUR
T1 - Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion
AU - Johanning, Jason M.
AU - Franklin, David P.
AU - Han, David C.
AU - Carey, David J.
AU - Elmore, James R.
PY - 2001
Y1 - 2001
N2 - Purpose: Nitric oxide (NO), frequently cited for its protective role, can also generate toxic metabolites known to degrade elastin. Both abdominal aortic aneurysms (AAAs) and inducible nitric oxide synthase (iNOS) are associated with inflammatory states, yet the relationship between NO production by iNOS and AAA development is unknown. The current study examines iNOS expression, NO production, and the effects of selective inhibition of iNOS by aminoguanidine in experimental AAA. Methods: An intra-aortic elastase infusion model was used. Control rats received intra-aortic saline infusion and postoperative intraperitoneal saline injections (Group 1). In the remaining groups, intra-aortic elastase infusion was used to induce aneurysm formation. These rats were treated with intraperitoneal injections of saline postoperatively (Group 2), aminoguanidine postoperatively (Group 3), or aminoguanidine preoperatively and postoperatively (Group 4). Aortic diameter and plasma nitrite/nitrate levels were measured on the day of surgery and postoperative day 7. Aortas were harvested for biochemical and histologic analysis on postoperative day 7. Results: Infusion of elastase produced AAAs (P < .001) with significant production of iNOS (P < .05) and nitrite/nitrate (P < .003) compared with controls. Selective inhibition of iNOS with aminoguanidine in elastase-infused aortas significantly reduced aneurysm size (P < .01) compared with elastase infusion alone. Aminoguanidine-treated rats displayed suppression of iNOS expression and plasma nitrite/nitrate production not significantly different from the control group. Histologic evaluation revealed equivalent inflammatory infiltrates in elastase-infused groups. Conclusion: Expression of iNOS is induced and plasma nitrite/nitrate levels are increased in experimental AAA. Inhibition of iNOS limits NO production and iNOS expression, resulting in smaller aneurysm size. NO production by iNOS plays an important role with detrimental effects during experimental aneurysm development.
AB - Purpose: Nitric oxide (NO), frequently cited for its protective role, can also generate toxic metabolites known to degrade elastin. Both abdominal aortic aneurysms (AAAs) and inducible nitric oxide synthase (iNOS) are associated with inflammatory states, yet the relationship between NO production by iNOS and AAA development is unknown. The current study examines iNOS expression, NO production, and the effects of selective inhibition of iNOS by aminoguanidine in experimental AAA. Methods: An intra-aortic elastase infusion model was used. Control rats received intra-aortic saline infusion and postoperative intraperitoneal saline injections (Group 1). In the remaining groups, intra-aortic elastase infusion was used to induce aneurysm formation. These rats were treated with intraperitoneal injections of saline postoperatively (Group 2), aminoguanidine postoperatively (Group 3), or aminoguanidine preoperatively and postoperatively (Group 4). Aortic diameter and plasma nitrite/nitrate levels were measured on the day of surgery and postoperative day 7. Aortas were harvested for biochemical and histologic analysis on postoperative day 7. Results: Infusion of elastase produced AAAs (P < .001) with significant production of iNOS (P < .05) and nitrite/nitrate (P < .003) compared with controls. Selective inhibition of iNOS with aminoguanidine in elastase-infused aortas significantly reduced aneurysm size (P < .01) compared with elastase infusion alone. Aminoguanidine-treated rats displayed suppression of iNOS expression and plasma nitrite/nitrate production not significantly different from the control group. Histologic evaluation revealed equivalent inflammatory infiltrates in elastase-infused groups. Conclusion: Expression of iNOS is induced and plasma nitrite/nitrate levels are increased in experimental AAA. Inhibition of iNOS limits NO production and iNOS expression, resulting in smaller aneurysm size. NO production by iNOS plays an important role with detrimental effects during experimental aneurysm development.
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U2 - 10.1067/mva.2001.111805
DO - 10.1067/mva.2001.111805
M3 - Article
C2 - 11241130
AN - SCOPUS:0035099471
SN - 0741-5214
VL - 33
SP - 579
EP - 586
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
IS - 3
ER -