BACKGROUND: In the present study, we employed an elastase infusion-dependent abdominal aortic aneurysm (AAA) model to examine inducible nitric oxide synthase (iNOS) expression in relation to cellular proliferation and apoptosis in this pathologic condition. Furthermore, we employed N-(3-(aminomethyl)benzyl)acetamidine (1400 W), a previously shown selective iNOS inhibitor, to further explore this relationship. METHODS: Adult male Wistar rats were randomized into separate groups. Group A served as a control and received an intra-aortic saline infusion, while groups B, C, and D received an intra-aortic elastase infusion according to standard protocols. The animals in group C were administered postoperatively the highly selective iNOS inhibitor, 1400 W, while rats in group D received regularly the same compound preoperatively and postoperatively. The animals were killed at postoperative days 7 and 14. Aorta diameter and nitric oxide (NO), nitrite/nitrate, and MDA levels were measured. iNOS expression was assessed by immunohistochemistry and Western blot analysis, while Ki-67 immunohistochemistry and TUNEL assay were used to evaluate cellular proliferation and apoptosis, respectively. RESULTS: Increased iNOS and NO levels accompanied aneurysm development in groups B, C, and D, but these levels were significantly lower in groups C and D, compared with group B. Interestingly, very low but detectable levels of iNOS were found in the control group, indicating a basal constitutive level. Cell growth parameters were augmented in group B compared with group A. In contrast, groups C and D exhibited a significant decrease of the cellular growth parameters but did not attain normal values. CONCLUSIONS: iNOS-derived NO is associated with the cellular growth parameters of the vessel cells, predominantly smooth muscle cells. Selective iNOS blockage ameliorates the cellular remodeling in AAAs.
BACKGROUND: In the present study, we employed an elastase infusion-dependent abdominal aortic aneurysm (AAA) model to examine inducible nitric oxide synthase (iNOS) expression in relation to cellular proliferation and apoptosis in this pathologic condition. Furthermore, we employed N-(3-(aminomethyl)benzyl)acetamidine (1400 W), a previously shown selective iNOS inhibitor, to further explore this relationship. METHODS: Adult male Wistar rats were randomized into separate groups. Group A served as a control and received an intra-aortic saline infusion, while groups B, C, and D received an intra-aortic elastase infusion according to standard protocols. The animals in group C were administered postoperatively the highly selective iNOS inhibitor, 1400 W, while rats in group D received regularly the same compound preoperatively and postoperatively. The animals were killed at postoperative days 7 and 14. Aorta diameter and nitric oxide (NO), nitrite/nitrate, and MDA levels were measured. iNOS expression was assessed by immunohistochemistry and Western blot analysis, while Ki-67 immunohistochemistry and TUNEL assay were used to evaluate cellular proliferation and apoptosis, respectively. RESULTS: Increased iNOS and NO levels accompanied aneurysm development in groups B, C, and D, but these levels were significantly lower in groups C and D, compared with group B. Interestingly, very low but detectable levels of iNOS were found in the control group, indicating a basal constitutive level. Cell growth parameters were augmented in group B compared with group A. In contrast, groups C and D exhibited a significant decrease of the cellular growth parameters but did not attain normal values. CONCLUSIONS:iNOS-derived NO is associated with the cellular growth parameters of the vessel cells, predominantly smooth muscle cells. Selective iNOS blockage ameliorates the cellular remodeling in AAAs.
Authors: Karlijn B Rombouts; Tara A R van Merrienboer; Johannes C F Ket; Natalija Bogunovic; Jolanda van der Velden; Kak Khee Yeung Journal: Eur J Clin Invest Date: 2021-11-21 Impact factor: 5.722