Poly(ADP-ribose) polymerase inhibition improves endothelin-1-induced endothelial dysfunction in rat thoracic aorta.

AIM: The aim of this study was to investigate whether poly(ADP-ribose) polymerase (PARP) inhibition improves endothelin-1 (ET-1)-induced endothelial dysfunction (ED). METHODS: Isolated rat thoracic aorta rings were incubated with ET-1 (10 nmol/L) in the presence or absence of either polyethylene glycol-superoxide dismutase (PEG-SOD; a cell-permeable superoxide radical scavenger, 41 U/mL) plus apocynin (a NADPH oxidase inhibitor, 300 µmol/L) or PJ34 (an inhibitor of polyADP-ribose polymerase, 3 µmol/L) for 18 h. Isometric tension studies were performed in response to acetylcholine (ACh; an endothelium-dependent vasodilator), sodium nitroprusside (SNP; an endothelium-independent vasodilator), and phenylephrine (Phe). PARP-1 and PAR (an end-product of PARP activity) expressions were evaluated by both Western blot and immunohistochemistry. RESULTS: Incubation of thoracic aorta rings with ET-1 resulted in a significant inhibition of the response to ACh, while SNP-induced relaxation was unaffected. The contractile response to Phe increased in arteries that were incubated with ET-1. PARP-1 and PAR expressions increased after ET-1 incubation. The diminished vasoreactivity as well as changes in expressions of PARP-1 and PAR in ET-1-incubated vessels were improved by both PEG-SOD plus apocynin and PJ34. CONCLUSION: Our studies demonstrate that ED induced by ET-1 seems to be effected via oxidative stress in the thoracic aorta endothelium with subsequent activation of the PARP pathway.

Ellagic acid-induced endothelium-dependent and endothelium-independent vasorelaxation in rat thoracic aortic rings and the underlying mechanism.

The present study first investigated the mechanisms of vasorelaxation induced by ellagic acid (EA), which is one of the major compounds extracted from the pomegranate in the rat thoracic aorta. Male Wistar rats aged 10 to12 weeks weighing 250-350 g were used for the present study. The animals were killed by decapitation, and thoracic aortas were immediately excised and placed in Krebs solutions, cleaned, and freed from surrounding connective tissue. The isolated arteries were cut into rings (4- to 5-mm long) and placed in 20-mL tissue chambers filled with Krebs solution. Initially, the aortic rings were equilibrated for 60 min until a resting tension of 1.0 gr. After the equilibration period, aortic rings were firstly contracted with phenylephrine to increase tone. Once a stable contraction was achieved, EA (10(-8) to 10(-4) M) was added cumulatively on aortic rings with or without endothelium into organ bath. To characterize the mechanisms involved in EA-induced vasorelaxant effect, the aortic rings were incubated with each inhibitor added to the bath for 30 min before phenylephrine was added to increase tone. The results of the present study have demonstrated in the rat thoracic aorta that EA causes vasorelaxations, which are partly modulated via endothelium-dependent mechanisms and through inhibition of calcium influx.