Ageing affects nitric oxide synthase, cyclooxygenase and oxidative stress enzymes expression differently in mesenteric resistance arteries

Abstract

1 Our aim was to study the role of nitric oxide (NO) and arachidonic acid pathways in the alpha(1)-adrenoceptor-mediated vasoconstriction in mesenteric resistance arteries from 3--4 and 22 to 23-month-old Sprague-Dawley rats. 2 The expression of NO synthase (NOS), cyclooxygenase (COX) isoforms, soluble guanylate cyclase, superoxide dismutase and the NAD(P)H oxidase subunits p22(phox) and p 47(phox) were determined. 3 The N(G)-nitro-l-arginine methyl ester, a non-selective NOS inhibitor, shifted to the left but indomethacin and NS 398, non-selective and selective COX-2 inhibitors, shifted to the right the concentration-response curve for the vasoconstriction by phenylephrine in both age groups. 4 Ageing up-regulated endothelial NOS and p22(phox) expression but did not modify COX, soluble guanylate cyclase, superoxide dismutase and p 47(phox) expression. 5 These data suggest that the observed enhancement of eNOS protein expression could constitute a compensatory mechanism to counter-regulate a chronic loss of NO possibly through increased superoxide anion production from NAD(P)H oxidase induced by age.

Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice

“…Besides NO, vasoconstrictor prostaglandins have also been implicated in the phatophysiology of vascular dysfunction during aging (Briones et al, 2005;Vanhoutte, 2009) and estrogen withdrawn (Dantas et al, 1999;Dantas et al, 2004). In our studies…”

“…V asoconstrictor prostanoids, such as thromboxane A 2 (TXA2), have also been implicated in the phatophysiology of vascular dysfunction during estrogen withdrawn (Dantas et al, 1999;Dantas et al, 2004) and aging (Briones et al, 2005;Vanhoutte, 2009) and play an important role in the regulation of vascular tone in the normal systemic female vasculature (Fulton and Stallone, 2002) , which involves the TXA2 receptor (TXA2R) (Li et al, 2008) .…”

Antioxidants Reverse Age-Related Collateral Growth Impairment

“…Although functional and structural changes are known to occur in the vasculature with age, the mechanisms responsible for impaired collateral growth are unclear. Increased oxidant stress, due to elevated reactive oxygen species (ROS) production or to decreased function of natural antioxidant pathways, has been shown to increase with age [5, 7, 8] and may be a factor in inhibiting compensatory remodeling. Nitric oxide (NO) is required for both normal vascular function and collateral growth [9, 10], and its bioavailability may be negatively impacted by oxidative stress via scavenging by superoxide [11] or by other related mechanisms, such as endothelial NO synthase (eNOS) uncoupling [12].…”

Female Vascular Senescence

“…Dysfunction of both endothelial and smooth muscle molecular signaling appear to occur during aging process and favors vasospasm, thrombosis, inflammation and abnormal cell migration and proliferation (Lakatta, 2003;Briones et al, 2005;Barton, 2010;Herrera et al, 2010). The presence of endothelial dysfunction in the elder has been largely associated with malfunctioning of vascular tissue resulting, in turn, into cardiovascular disease (including atherosclerosis, hypertension or coronary artery disease) (Lakatta, 2003;Herrera et al, 2010), as well as renal dysfunction (Schmidt et al, 2001;Erdely et al, 2003), Alzheimer (Price et al, 2004) and erectile dysfunction (Burnett, 2006).…”

“…Several mechanisms to explain a reduction on NO production have been pointed out and include: 1) a decrease on the expression of endothelial NO synthase (eNOS) (Briones et al, 2005;Yoon et al, 2010); 2) a deficiency on NO precursor (Larginine) (Santhanam et al, 2008) and eNOS cofactor (tetrahydrobiopterin -BH 4 ) (Yoshida et al, 2000;Eskurza et al, 2005); or 3) an increase of endogenous eNOS inhibitors (asymmetric dimethylarginine -ADMA) (Xiong et al, 2001;Kielstein et al, 2003). On the other hand, strong evidences support the hypothesis that age-associated increase in oxidative stress, and consequent production of superoxide anion (O 2 -) is a potent contributor to lowering NO bioavailability and increasing endothelial dysfunction (Jacobson et al, 2007;RodriguezManas et al, 2009).…”