Background and Objection: Peroxynitrite (ONOO-) has been demonstrated to have cytotoxic effects on vasculature. However, there is still a lack of direct evidence for the vasorelaxation dysfunction by ONOO- in aging resistance arteries, and the mechanism is unknown. Method: Young (3-4 months olds) and aging (20 months olds) male SD rats were randomly randomized to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger; 3mg/kg/3 days) via intraperitoneal injection for 2 weeks. Animals were euthanized after anaesthesia (chloral hydrate via i.p., 30mg/kg). In the present study, the vasorelaxation of resistance arteries in young or aging rats was determined in vitro; NO content was determined by a colorimetric assay; the expression of tyrosine nitration (NT), soluble Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP) and phosphorylated VASP (P-VASP) in resistance arteries were detected by immunohistochemical staining. Result: Endothelium-dependent dilation in aging resistance arteries was lower than young rats (aging vs. young: 50.4%±2.9% vs. 68.0%±4.5%, P<0.01, analyzed by t-test; n>4). And the endothelium-independent dilation in aging resistance arteries remained constant (P>0.05, analyzed by t-test; n> 4). FeTMPyP treatment normalized endothelial-dependent vasorelaxation in aging resistance arteries (aging+FeTMPyP vs. aging: 61.5%±3.5% vs. 50.4%±2.9%, P<0.05, analyzed by t-test; n>4). NO content was increased in serum from aging rats compare with young rats (nmol NOx/ ml plasma; young vs. aging: 3.3±1.4 vs. 5.3±1.0, P<0.05, analyzed by t-test; n>5). NT (biomarker of ONOO-) expression was elected in resistance arteries from aging rats (P<0.05, analyzed by t-test; n>3). And NT expression was suppressed by FeTMPyP treatment (P<0.05, analyzed by t-test; n>3). The expression of sGC was not significantly different between aging and young resistance arteries (P>0.05, analyzed by t-test; n>3), but the P-VASP/VASP ratio (biochemical marker of NO-sGC-cGK signaling) decreased in aging resistance arteries, which was reversed by FeTMPyP treatment in vivo (P<0.05, analyzed by t-test; n>3). Conclusion: The present study suggested that ONOO- is responsible for the decline of endothelial-dependent vasorelaxation in aged resistance arteries, and this effect likely involves the dysfunction of the NO-sGC-cGK pathway. Key word: Aging; Peroxynitrite; Resistance arteries; Vasorelaxation function
Epithelia and Smooth Muscle Interactions in Health and Disease (Dublin) (2013) Proc Physiol Soc 30, PC25
Poster Communications: Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in aging rats: involvement with NO-sGC-cGK pathway
L. Ma1, K. Wang1, J. Shang1, C. Cao2, P. Zhen3, X. Liu1, W. Wang1, H. Zhang1, Y. Du1, H. Liu1
1. Department of Physiology and Pathophysiology, Capital Medical University, Beijing, China. 2. Department of Chest Surgery, First Hospital of Longyan, Fujian Medical University, Longyan, China. 3. Department of Pathology, Luhe Hospital, Capital Medical University, Beijing, China.
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