Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat.

Abstract

To determine if oxygen-derived free radicals are mediators of endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats (SHR), the mechanism of contraction to xanthine plus xanthine oxidase was studied. Rings, with and without endothelium, of thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and SHR were suspended in organ chambers for isometric tension recording. Oxygen-derived free radicals caused concentration-dependent contractions; these contractions were twice as large in the aortas of SHR than in WKY rats. Deferoxamine reversed the response to xanthine oxidase to a small relaxation. Either allopurinol, superoxide dismutase, or catalase, or the combination of superoxide dismutase plus catalase reduced the contractions. Diltiazem inhibited the response to xanthine oxidase; in contrast, phentolamine plus propranolol did not affect it. Indomethacin and meclofenamate, but not tranylcypromine or dazoxiben blocked the contractions. Endotheliumdependent contractions to acetylcholine in aortas from the SHR were not affected by deferoxamine or superoxide dismutase plus catalase. These data suggest that hydroxyl radicals cause contractions in the rat aorta, which are dependent on extracellular calcium and mediated by activation of the cyclooxygenase in the vascular smooth muscle. The augmented contractions in the hypertensive strain are due to an increased reactivity of the smooth muscle to oxygenderived free radicals. However, the lack of effect of the scavengers on endothelium-dependent contractions to acetylcholine suggests that the endothelium-derived contracting factor is chemically different from oxygen-derived free radicals. (Hypertension 1989;13:859-864)

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

“…This observation resembles the findings obtained in the aorta of the spontaneously hypertensive rat (Auch-Schwelk et al, 1989;Yang et al, 2002). These observations support the concept that the superoxide anions inside endothelial cells are the primary oxidative contributor to endothelium-dependent contractions.…”

“…Ferrous ions catalyse interactions between hydrogen peroxide and superoxide anions, producing hydroxyl radicals. Deferoxamine, an iron chelator that scavenges hydroxyl radicals (for example, Auch-Schwelk et al, 1989), reduced the response to A23187, indicating that hydroxyl radicals are also involved in endothelium-dependent contractions in the femoral artery of rats with STZ-induced diabetes. Taken together, the findings of the present study strongly suggest that an increase in intracellular concentration of Ca 2 þ leads to the generation of superoxide anions, which are converted by SOD to hydrogen peroxide that is further transformed to hydroxyl radicals, responsible in part for the endothelium-dependent contractions observed in arteries of the diabetic rats.…”

“…The hyperresponsiveness of the femoral artery from the diabetic rat can be explained in part by the hyper-responsiveness of the thromboxane prostanoid receptors of its vascular smooth muscle (Shi et al, 2007). The fact that indomethacin, the inhibitor of cyclooxygenase, inhibited the response suggests that the hydroxyl radicals activate the production of vasoconstrictor metabolites of arachidonic acid, presumably endoperoxides or thromboxane A 2 , in vascular smooth muscle (Auch-Schwelk et al, 1989;Yang et al, 2002Yang et al, , 2003bWolin, 2004). These data reached in functional studies with exogenous hydrogen peroxide suggest that this peroxide, at least, could be the precursor of endothelium-derived contracting factor in the femoral artery of rats with diabetes.…”

Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats

“…However, this can not explain the present ®ndings given that impaired relaxation in response to ACh in aortas from SHR fed the high salt diet could not be restored by pretreatment with superoxide dismutase plus catalase. Similar data have been reported for the aorta of SHR (Auch-Schwelk et al, 1989) and the forearm vasculature of patients with essential hypertension (Garcia et al, 1995). Furthermore, it is possible that sGC expression may be inhibited by overproduction of NO, namely the presence of a negative autoregulatory mechanism (Scott & Nakayama, 1998;Filippov et al, 1997;Papapetropoulos et al, 1996).…”

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

“…33 Elevated SUA levels were also associated with the increased generation of free radicals 34 and oxidative stress, which could abolish endothelium-dependent vasodilatation, leading to hypertension. 35 However, other studies have suggested that UA was an effective antioxidant, 36,37 and the exact role of UA in oxidation (pro-oxidant or antioxidant) remains to be elucidated. Further studies are needed to clarify the role of UA in the context of hypertension and MetS.…”