Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery.

Abstract

Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endothelial NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation.Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17 ␤ (E 2 ) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 mol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats ( P Ͻ 0.0006 vs. young rats, n ϭ 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10 Ϫ 10 -10 Ϫ 5 mol/liter) were also reduced in aortas from old as compared with young rats ( n ϭ 6, P Ͻ 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r ϭ 0.916, P Ͻ 0.0018 and r ϭ 0.961, P Ͻ 0.0001, respectively, n ϭ 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age ( n ϭ 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups ( n ϭ 6, NS).Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.

Age-Dependent Impairment of Angiogenesis

“…Angiogenesis is a complex process that includes activation, migration, and proliferation of endothelial cells. 19 Recent studies [21][22][23][24] have indicated that the integrity of endothelial cell function may be compromised as a function of advanced age. We confirmed that endothelial function was abnormal in old versus young rabbits by documenting impaired vasodilation in response to the endothelium-dependent vasodilator acetylcholine in vivo and reduced release of NO from isolated blood vessels studied ex Representative examples of collateral vessel formation in old rabbits (A), old VEGF-treated rabbits (B), young rabbits (C), and young VEGF-treated rabbits (D).…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…Endothelial dysfunction may be due to diminished bioavailability of nitric oxide (Taddei et al, 2001; Tschudi et al, 1996). Arterial stiffness results primarily from loss of elastic fibers and an increase in collagen (Fritze et al, 2012).…”

Superoxide as a Messenger of Endothelial Function

“…Direct in situ measurements of NO were carried out using a three-electrode system: a porphyrinic NO microsensor as the working electrode (anode), a platinum wire auxiliary electrode (cathode), and a standard calomel reference electrode (Azhar et al, 1995;Tschudi et al, 1996). Amperometric mode detection was used at a constant potential, equal to the peak potential for NO oxidation of the working electrode.…”

“…This enzyme is largely membrane associated as a result of NH 2 -terminal myristoylation (Pollock et al, 1991), a reaction which regulates enzymatic biological activity (Sessa et al, 1993;Busconi and Mitchel, 1993). Endothelium-dependent relaxation 8-2 declines with increasing age (Tschudi et al, 1996). The underlying cellular and molecular mechanisms associated with age-related endothelial dysfunction have not been elucidated, but might involve: (a) changes in expression and/or activity of eNOS (Cernadas et al, 1998), (b) increased breakdown of NO due to an augmented production of • O 2 - (Gryglewski et al, 1986), or (c) a gradual loss of antioxidant capacity (Azhar et al, 1995), which normally provides cellular protection against reactive oxygen species.…”