Constitutive activation of α‐adrenoreceptors with advanced age impairs rapid onset vasodilation: key role for feed arteries (674.6)

Abstract

Rapid onset vasodilation (ROV) is depressed in second‐order arterioles of the mouse gluteus maximus muscle (GM) during advanced age (PMC2911225). However the extent to which aging impairs ROV is unknown. Therefore, we tested the hypothesis that advanced age attenuates ROV throughout microvascular resistance networks. In Young and Old male C57BL/6 mice (4 and 24 mo; n=6/group), the inferior gluteal motor nerve was stimulated (0.1ms, 30V, 100 Hz) to evoke single tetanic contractions. Within 1 s following 500 ms contraction, ROV was manifested in first (1A)‐, second (2A)‐ and third (3A)‐order arterioles and ascended into feed arteries (FA); peak dilations occurred at ~ 4s in all branches. Thus ROV was coordinated both temporally and spatially. Relative to respective maximal diameters, peak dilation increased with vessel branch order (P<0.05) yet was attenuated consistently (P<0.05) in Old vs. Young: FA (25±3 vs. 34±5%) < 1A (46±7 vs. 64±4%) < 2A (61±7 vs. 72±5%) < 3A (63±4 vs. 77±6%). Inhibition of α‐adrenoreceptors (αAR) with phentolamine (1 µM) improved dilations in Old (P<0.05) an additional 20±5% in FA, 7±2% in 1A, 16±3% in 2A and 12±3% in 3A. Thus, constitutive activation of αAR with advanced age impairs ROV with relatively greatest effect in FA. This consequence of advanced age will restrict total muscle blood flow upon the onset of muscle contraction and can thereby impede transitioning from rest to physical activity.Grant Funding Source: Supported by NIH R01 HL086483