Disfunção endotelial e nitrérgica: prevenção e/ou reversão por antioxidantes naturais e componetes do mediador putativo da insulina

Abstract

The endothelium is a very active endocrine organ regulating many important vascular functions related to haemodynamics and blood pressure control. For instance it actively regulates the vessel tonus, the thrombotic status of blood, atherogenesis and angiogenesis, only to mention a few. This organ as anyone is subject to dysfuction and even failure. Among the major risk factors for endothelial dysfunction (ED) are diabetes and senescence."* The endothelial-dependent relaxant response to acetylcholine (ACh) compared to the endothelial-independent relaxation induced by a nitrovasodilatador was used as a method to measure endothelial function in resistance (mesenteric, cavernous and renal) and conductance (aorta) vessels. Wc find that both diabetes and senescence strongly blunts the endothelial-dependent response in either resistance or conductance vessels. The administration of rutin (50 mg/kg/12h; p.o) or lipoic acid (LA; 20 mg/Kg/12h; p.o) to both diabetic (Db) and senescent rats was shown to be effective in the prevention of ED in aorta and arteriolar mesenteric bed (AMB). The calculated ED for aorta was 51.9 ± 4.6% compared with 14.1 ± 2.4% (p<0.05) in the rutin-treated group and 44.7±3.7% in the LA- treated group. The calculated ED for diabetic AMB was 44.6±5.8% compared with 21.4 ± 2.8% (p<0.05) in the rutin group and 24.8±3.7% (p<0.05) in the AL group. The same pattern was observed in the renal vascular bed (RVB) and rabbit corpus envernosus (RbCC). In this tissue 1-hour incubation with 1 pM de rutin or AL reversed ED. In RVB the maximal relaxant response to ACh was 16.0±2.0% compared with 42.0±3.4% (p<0.05) obtained in rutin-treated tissues and 31.0±3.9% (p<0.05) in AL. The maximal nitrergic response of RbCC to electrical ficld stimulation (20 V; 0,5 ms e 16 Hz) was 89.6±6.0% in control euglycemic animais compared to 37.0±4.0% (p<0.05) in diabetic RbCC. Previous incubation with rutin restored this relaxation to 63.8±4.8% (p<0.05 Db+vchicle vs. Db+ rutin). The endothelial-dependent relaxation to ACh in RbCC was also blunted in diabetic tissues (euglycemic= 87.0±8.0% vs. Db=27.8±3.8%) and was also restored towards normal (74,0±7,0%) leveis in rutin-treated tissues. In addition, the other antioxidant agents used, i.e., catechin and glutathione (GSH) also partially reversed ED in diabetic and senescent vascular tissues. Similarly, in senescent vascular tissues rutin and AL significantly reversed ED. The calculated ED for aorta was 55.0±5.2% compared with 13.5±1.3% (p<0.05) in the rutin-treated group and 29.3±3.4% (p<0.05) in AL-treated tissues. The same profile was shown in the AMB with 53.4±4.2% ED compared with 6.1±1.3% in rutin-treated tissues and 27.9±3.7% in the AL-treated group. The administration of the putativc insulin- mediators (20 mg/Kg/12h, v.o) partially prevented or reversed ED in diabetic and senescent vascular tissues. Similarly, in senescent vascular tissues rutin and AL significantly reversed ED. The calculated ED for aorta was 55.0±5.2% compared with 13.5±1.3% (p<0.05) in the rutin-treated group and 29.3±3.4% (p<0.05) in AL-treated tissues. The same profile was shown in the AMB with 53.4±4.2% ED compared with 6.1±1.3% in rutin-treated tissues and 27.9±3.7% in the AL-treated group. The administration of the putativc insulin- mediators (20 mg/Kg/12h, v.o) partially prevented or reversed ED in diabetic tissues of rats and rabbits. They were also shown to have superoxide scavenger activity in vitro and potentiate the relaxant response of senescent aortas to exogenous nitric oxide administration. These compounds may have a beneficiai outeome as adjuvants in-preventive or curative protocols for endothelial dysfunction associated with diabetes or senescence.