Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm.

摘要: Angiotensin-II and oxidative stress are involved in the genesis of aortic aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS) deletion or uncoupling. The purpose this work was to study function wild-type C57BL/6 (BL) transgenic mice expressing h-angiotensinogen h-renin genes (AR) subjected either control, high-salt diet plus treatment with NO-synthase inhibitor, N-ω-nitro-l-arginine-methyl-ester (l-NAME; BLSL ARSL). showed moderate increase blood pressure, while ARSL became severely hypertensive. Seventy-five percent developed characterized major histo-morphological changes associated an NADP(H) oxidase-2 (NOX2) expression. Contractile responses (KCl, norepinephrine, U-46619) were similar four groups mice, relaxations not affected AR. However, ARSL, endothelium-dependent (acetylcholine, UK-14304) significantly reduced, dysfunction aortae without aneurysms. impairment unaffected catalase, superoxide-dismutase mimetic, radical scavengers, cyclooxygenase inhibition, TP-receptor blockade could be attributed sGC oxidation. Thus, is severe hypertension model developing aneurysm. A vascular dysfunction, involving both (reduced role NO) smooth muscle cells, precedes aneurysms formation and, paradoxically, does appear involve stress.