Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC344

Poster Communications

Reactive oxygen species potentiate vasodilator effect of nitric oxide donor with gold nanoparticles in aortas from renal hypertensive rats

B. R. Silva1, R. S. da Silva2, L. M. Bendhack2

1. Pharmacology, 1School of Medicine of Ribeir

Nitric Oxide (NO) plays important role in the control of the vascular tone, but it can be degraded by reactive oxygen species that are higher in renal hypertensive rat (2K1C) aorta and impair the vasodilation induced by NO donors such as Ru-4PySH.AIM: to investigate the relaxation induced by the complex AuNPs-{Ru-4PySH}n in aortic rings from normotensive (2K) and two kidney one clip 2K1C and the effects of superoxide anion (O2-) scavenger (Tiron) and catalase on hydrogen peroxide (H2O2) on the contractile response induced by phenylephrine (PE) and on the relaxation induced by the NO donor. METHODS: Male rats (180-200g) were anesthetized with tribromoethanol 0.5% (10ml Kg-1, ip) and the left renal artery was partially obstructed with a silver clip or sham surgery. After six weeks, rats with blood pressure>160mmHg were considered 2K1C. They were anesthetized with isoflurane by inhalation and killed to remove the aorta. Denuded aortic rings were placed in a system to measure the isometric tension. To evaluate the effects of Tiron (0.1mM, 1mM) and Catalase (30,90,150,300 UI/mL),cumulative concentration-effect curves (CCEC) were done for PE in 2K and 2K1C with or without Tiron/catalase. Then, CCEC for AuNPs-{Ru-4PySH}n were constructed in 2K and 2K1C aortas pre-contracted with PE. It was evaluated the efficacy (ME) and potency (pD2) of PE and AuNPs-{Ru-4PySH}n. The experimental procedures were approved by the Ethics Commitee of the University of São Paulo (N° 156/2009). RESULTS AND DISCUSSION: PE induced similar contraction in 2K (ME: 2.5±0.2g; pD2: 7.93±0.10; n=8) and 2K1C aortas (ME: 2.6±0.2g; pD2: 7.89±0.08; n=9), which was reduced by Tiron in 2K (Tiron 0.1mM ME: 2.4±0.2g; pD2: 7.60±0.06; n=8 and Tiron 1mM ME: 1.7±0.4g; pD2: 7.32±0.04; n=4; p<0.001), but it did not alter the contractile response to PE in 2K1C aorta. Catalase also reduced the contraction to PE in 2K-1C (ME: 1.5±0.2g; pD2: 7.58±0.07; n=4; p<0.001) with no effect in 2K aorta. AuNPs-{Ru-4PySH}n was more potent in 2K1C (ME:110.9±6.3%; pD2: 6.29±0.04; n=4; p<0.05) than in 2K (ME: 99.1±1.0%; pD2: 6.10±0.04; n=4). Tiron or catalase had no effect in the vasodilatation of 2K aorta induced by AuNPs-{Ru-4PySH}n, but they reduced its potency in 2K1C (Tiron ME: 109.3±5.5%; pD2: 5.22±1,00; n=3; and Catalase, ME: 107.1±7.1%; pD2: 5.60±0,17; n=4; p<0.001). Our results suggest that O2- positively modulates the contractile response to PE in normotensive, and H2O2 has this effect only in 2K1C aorta. Our results demonstrated that although PE induced similar contraction in 2K and 2K1C aorta, the vasodilatation induced by AuNPs-{Ru-4PySH}n was more potent in 2K1C than in 2K. It seems that ROS potentiate the vasodilatation induced by AuNPs-{Ru-4PySH}n.

Where applicable, experiments conform with Society ethical requirements