Multivessel Analysis of Progressive Vascular Aging in the Rat: Asynchronous Vulnerability Among Vascular Territories

Aging induces vascular dysfunction, representing the major risk factor for cardiovascular disease. Our aim was to ascertain specific vulnerability of vascular territories to aging by evaluating the progressive impact of aging on vascular function in four different vascular beds: aorta, mesenteric artery (MA), coronary artery (CA), and penile corpus cavernosum (CC) from 3, 6, 9, 12, 20 or 24 months-old male rats. Contractile/relaxant responses were evaluated in organ chambers (A/CC) and wire myographs (MA/CA). Relationships of systemic biomarkers with endothelial function impairment were also determined. Although all vessels manifested aging-related impairment in endothelial vasodilation, CA was the most impacted by aging considering the onset (at 6 months) and magnitude of endothelial dysfunction (reduction by 1.5 log units in the concentration required for 50% of maximal relaxation for acetylcholine). HO-induced vasodilations were progressively reduced by aging in aorta, CC and CA while NO-donor-induced vasodilation was impaired by aging only in CA. Serum asymmetric dimethylarginine significantly correlated to endothelial decline in aorta, MA, and CC, while HOMA-IR was significantly associated with endothelial dysfunction in CA and MA. CA are especially vulnerable to aging-related vascular dysfunction. Correlations of vascular dysfunction with systemic biomarkers differ among vessels, further suggesting heterogeneity in aging-induced vascular impact.