Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Figures

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  Figure 1. Insulin–mediated vasorelaxation. Insulin (3 × 10−8 to 3 × 10−6 mol/L)–mediated vasorelaxation at cumulative concentration–response curves in (a) endothelium–intact rings and (b) endothelium–denuded rings in the 24wk-WKY, 48wk-WKY, 24wk-SHR, and 48wk-SHR groups. The vasorelaxing responses were expressed as the percentages of the 0.1 μmol/L PE–induced precontractile force. Abbreviation: PE, phenylephrine. * p < 0.05, significant differences from 24wk-WKY; # p < 0.05, significant differences from 48wk-WKY; † p < 0.05, significant differences from 24wk-SHR; n = 8 in each group.

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  Figure 2. IGF-1–mediated vasorelaxation. IGF-1 (10−9 to 10−7 mol/L)–mediated vasorelaxation at cumulative concentration–response curves in (a) endothelium–intact rings and (b) endothelium–denuded rings in the 24wk-WKY, 48wk-WKY, 24wk-SHR, and 48wk-SHR groups. The vasorelaxing responses were expressed as the percentages of the 0.1 μmol/L PE–induced precontractile force. Abbreviation: PE, phenylephrine. * p < 0.05, significant differences from 24wk-WKY; # p < 0.05, significant differences from 48wk-WKY; † p < 0.05, significant differences from 24wk-SHR; n = 8 in each group.

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  Figure 3. Vasorelaxation after the pretreatment of nitro-L-arginine methyl ester (L-NAME) and wortmannin. (a) Insulin (10−6 mol/L)-mediated vasorelaxation and (b) IGF-1 (3 × 10−8 mol/L)-mediated vasorelaxation after the pretreatment of L-NAME and wortmannin in the 24wk-WKY, 48wk-WKY, 24wk-SHR, and 48wk-SHR groups. The vasorelaxing responses were expressed as the percentages of the 0.1 μmol/L PE-induced precontractile force. Abbreviation: PE, phenylephrine.* p < 0.05, significant differences from 24wk-WKY; # p < 0.05, significant differences from 48wk-WKY; † p < 0.05, significant differences from 24wk-SHR; 𝛼 p < 0.05, significant differences from no inhibitors; n = 8 in each group.

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  Figure 4. Serum nitrate/nitrite concentration in the 24wk-WKY, 48wk-WKY, 24wk-SHR, and 48wk-SHR groups. a p < 0.05, significant differences from 24wk-WKY; b p < 0.05, significant differences from 48wk-WKY; c p < 0.05, significant differences from 24wk-SHR; n = 8 in each group.

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  Figure 5. Serum levels of malondialdehyde (MDA), catalase activity, and total antioxidant capacity (TAC). (a) Serum MDA concentration, (b) catalase activity, and (c) TAC in the 24wk-WKY, 48wk-WKY, 24wk-SHR, and 48wk-SHR groups. a p < 0.05, significant differences from 24wk-WKY; b p < 0.05, significant differences from 48wk-WKY; c p < 0.05, significant differences from 24wk-SHR; n = 8 in each group.

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  Figure 6. The proposed scheme demonstrating potential mechanisms involved in the impaired insulin- and IGF-1-mediated vascular relaxation in age-related hypertension. The excessive production of ROS and antioxidant deficiency in either aging or hypertension reduced NO production and consequently impaired insulin- and IGF-1-mediated vascular relaxation. Furthermore, our finding indicated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in aging-related hypertension, which was partly attributed to the reduced NO production and imbalance of oxidative and antioxidant activities in hypertension. Ins, insulin; IGF-1, insulin-like growth factor-1; R, receptors; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; eNOS, endothelial nitric oxide synthase; MDA, malondialdehyde; CAT, catalase activity; TAC, total antioxidant capacity; ↑, increasing; ↑↑, more increasing; ↓, decreasing; ↓↓, more decreasing.