Mechanism of cerebral arteriolar abnormalities after acute hypertension

Abstract

Acute severe hypertension induced by intravenous norepinephrine or angiotensin in anesthetized cats equipped with a cranial window caused prolonged arteriolar vasodilation associated with reduced responsiveness to arterial hypercapnia or hypocapnia and passive response to changes in arterial blood pressure. Scanning and transmission electron microscopy of such pial arterioles showed discrete destructive endothelial lesions the density of which correlated with the degree of vasodilation. Abnormalities of the vascular smooth muscle were seen in all dilated arterioles but affected only a small number of smooth muscle cells. The oxygen consumption of pial arterioles from cats subjected to hypertension was significantly reduced in comparison to that of vessels from normal animals. The arteriolar abnormalities induced by hypertension were inhibited by pretreatment with inhibitors of cyclooxygenase (indomethacin or AHR-5850) or by topical application on the brain surface of scavengers of free oxygen radicals (mannitol or superoxide dismutase). The results suggest that the mechanism of the arteriolar abnormalities from acute hypertension involves a sudden increase in prostaglandin synthesis that leads to generation of free oxygen radicals.

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.…”

“…Although the pathogenesis of free radicals in hypertension is incompletely understood, many sources are possible, including free radical generation by polymorphonuclear leukocytes and enhanced production of radical species and oxidants by endothelium and smooth muscle cells. 5,11,41 Cellular oxidative modification of cholesterol is thought to involve endothelial-and macrophagederived reactive oxygen species. 36,42,43 Hypertension, which increases arterial wall thickness and oxygen diffusion, produces medial hypoxia and steep oxygen tension gradients within the wall.…”

“…[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.…”

Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo.

“…En-dothelial damage ranged from discrete endothelial lesions in pial arterioles 4 and intestinal arterioles 5 to disruption of cellular junctions and increases in vascular permeability in mesenteric vessels 6 and focal areas of endothelial denudation and platelet adherence in mesenteric arterioles. 7 In the cerebral circulation, acute hypertension not only damaged pial artery endothelium but also abolished dilation to acetylcholine and resulted in constriction of pial arteries to acetylcholine.…”

Superoxide dismutase decreases mortality, blood pressure, and cerebral blood flow responses induced by acute hypertension in rats.

“…These abnormalities are known to be caused by cyclooxygenase-derived free radicals since they can be prevented by cyclooxygenase inhibitors and oxygen radical scavengers. 6 ' 7 Additionally, we have very recently shown that the increases in cerebrovascular permeability and brain water content caused by norepinephrine-induced hypertension can be prevented by the systemic administration of superoxide dismutase. 8 In recent years, investigators have become interested in the endothelium and its generation of relaxing factors.…”