Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension.

Abstract

The appearance of superoxide anion radical in cerebral extracellular space during and after acute hypertension induced by intravenous norepinephrine was investigated in anesthetized cats equipped with cranial windows. Superoxide was detected by demonstrating the presence of superoxide dismutase-inhibitable reduction of nitroblue tetrazolium. The superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 4.1 +/- 1.61 nM/min per cm2 during hypertension and 4.55 +/- 0.62 nM/min per cm2 one hour after hypertension had subsided. During norepinephrine administration in the absence of hypertension, the superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 0.44 +/- 0.17 nM/min per cm2. The reduction of nitroblue tetrazolium during hypertension was also inhibited by prior treatment of the brain surface with phenylglyoxal at pH 10, to induce irreversible inhibition of the anion channel. The results show that acute hypertension is associated with the generation of superoxide which enters the extracellular space of the brain via the anion channel. Following hypertension, the sustained vasodilation caused by acute hypertension was inhibited significantly by topical application of superoxide dismutase and catalase, showing that it was due in part to superoxide and other radicals derived from it. The vasodilator response of cerebral arterioles to topical acetylcholine was converted to vasoconstriction following acute hypertension, and restored to vasodilation following topical application of superoxide dismutase and catalase. The results show that superoxide and other radicals generated after acute hypertension interfere with acetylcholine-induced endothelium-dependent vasodilation, probably because they destroy the endothelium-derived relaxant factor.

Probucol Reduces Oxysterol Formation in Hypertensive Rabbits

“…However, oxygen-derived free radicals have been suggested to participate in the pathogenesis of hypertensive vascular disease by increasing vascular permeability and contractility as well as by inducing cellular injury, the interpretation of which is based on the inhibitory effects of free radical scavengers. [11][12][13]40 The biological effects seen with oxygen-derived free radicals noted above also occur with ChOx.…”

“…[7][8][9][10] However, only limited information concerning peroxidative processes in hypertension and their modification by antioxidants is available. [11][12][13][14][15][16] Because cholesterol oxides (ChOx) have been ubiquitously identified in human plasma and atheromatous lesions, their involvement in the atherogenic process is receiving increasing scrutiny. [17][18][19][20][21] ChOx may influence the atherogenic process in several ways, since they are cytotoxic toward the cellular components of the arterial wall, [22][23][24] increase vascular permeability, 25 promote cholesterol ester formation and accumulation, 26 -28 inhibit prostaglandin I 2 synthesis by endothelial cells, 29 and perturb cholesterol biosynthesis.…”

Revascularization After Myocardial Infarction

“…Moreover, they would have found extensive evidence to support the hypothesis that vitamin C exerts certain effects because it is an antioxidant, as illustrated in my review on the possible role of oxidative stress in hypertension, published in 1993. 11 In fact, my studies showed that the same effect observed with vitamin C can be reproduced with 2 other antioxidants, thiopronine and glutathione, respectively. 9,10 The question of missing citations is surely an important one, and particularly so when the paternity of a finding or concept of some value is to be attributed.…”

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

“…We used cerebral pial arteries that have BBB properties [1,26] to investigate changes in permeability in response to ovariectomy and estrogen replacement in vitro. In cerebral endothelium that comprised the BBB, transcellular transport is low under normal conditions, but increases substantially under pathologic conditions in which barrier permeability is enhanced leading to vasogenic edema [19,34,50]. One of the earliest microscopic findings in an experimental animal model of acute hypertension (i.e., hypertensive encephalopathy) is an increased rate of pinocytosis in the cerebrovascular endothelium of arteries and arterioles, which allows significant passage of fluid and molecules into the brain [19,34].…”

“…Estrogen is a known antioxidant [15,32,33] and has been reported to inhibit membrane lipid peroxidation [2], thereby possibly attenuating the increased BBB permeability caused by free radical generation that is known to occur during acute hypertension and other brain injuries [41,50]. However, given that the level of estrogen in the OVX+E group was greater than CTL, estrogen replacement would be expected in this case to have a greater antioxidant effect and restore permeability to control levels.…”