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We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor N-nitro-l-arginine methylester or the antioxidant tempol. Structure was evaluated by media-lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by N-nitro-l-arginine methylester on ACh was inversely related to age in both groups (P<0.0001) and blunted in HT versus NT for each age range. In NT, tempol enhanced endothelial function in the oldest subgroup; in HT, the potentiating effect started earlier. HT showed an increased M/L (P<0.001) versus control. In both groups, M/L was directly related to age (P<0.0001). M/L was greater in HT, starting from 31 to 45 years range. A significant age-hypertension interaction occurred (P=0.0009). In NT, intravascular superoxide emerged in the oldest subgroup, whereas it appeared earlier among HT. Among NT, aged group displayed an increment of collagen fibers versus young group. In HT, collagen deposition was already evident in youngest, with a further enhancement in the aged group. In small arteries, ageing shows a eutrophic vascular remodeling and a reduced nitric oxide availability. Oxidative stress and fibrosis emerge in advanced age. In HT, nitric oxide availability is early reduced, but the progression rate with age is similar. Structural alterations include wide collagen deposition and intravascular reactive oxygen species, and the progression rate with age is steeper. [ABSTRACT FROM AUTHOR]

Essential hypertensive patients show a reduced nitric oxide availability secondary to oxidative stress generation in peripheral microcirculation. Cyclooxygenase (COX) contributes to reduce nitric oxide availability We assessed the possible vascular sources of oxidative stress, including COX-l, COX-2, and nicotinamide adenine dinucleotide phosphate oxidase, as determinants of endothelial dysfunction in small arteries isolated from essential hypertensive patients or normotensive controls. Small arteries were dissected after subcutaneous fat biopsies and evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation was assessed by acetylcholine, repeated under NG-nitro-L-arginine methyl ester, SC-560 (COX-1 inhibitor), DuP-697 (COX-2 inhibitor), ascor acid, or the nicotinamide adenine dinucleotide phosphate oxidase inhibitors apocynin or diphenylene iodonium. Vascular oxidative stress generation (fluorescent dihydroethidium), COX-1 and COX-2 expression (Western blot), and localization (immunohistochemistry) were also assessed. In controls, response to acetylcboline was blunted by NG-nitro-L-arginine methyl ester (P<0.001) and unmodified by SC-560, DuP-697, or ascorbic acid. In hypertensi patients, relaxation to acetylcholine was blunted, resistant to NG-nitro-L-arginine methyl ester or SC-560, an enhanced (P<0.01) by DuP-697, apocynin, or diphenylene iodonium (P<0.05). Furthermore, in hypertensiv patients, response to acetylcholine was normalized by ascorbic acid or apocynin+DuP-697. Intravascular oxidative stress generation was enhanced in hypertensive patients, decreased (P<0.01) by DuP-697, partly attenuated by apocynin or diphenylene iodonium, and prevented by ascorbic acid. Enhanced COX-2 expression and localization in the vascular media of hypertensive patients were also detected. In small resistance arteries of essential hypertensive patients, COX-2 is overexpressed and reduces nitric oxide availability. COX-2 represent a major source of oxidative stress generation, whereas nicotinamide adenine dinucleotide phosphate oxidase plays a minor, but significant, role in promoting superoxide generation. [ABSTRACT FROM AUTHOR]

This article determines whether cyclooxygenase (COX)-1 or COX-2 participate in the angiotensin II-induced endothelial dysfunction in murine mesenteric small arteries. To induce endothelial dysfunction, nitric oxide availability should be minimized and reactive oxygen species must increase. A comparison of the two COX isoenzymes is discussed. While COX-1 is expressed to produce physiologically relevant prostanoids, COX-2 is regarded as an inducible isoform.