Angiotensin II in the Elderly

Abstract

Abstract-Exercise hyperemia is attenuated in the elderly, which may be attributed to local vasoregulatory pathways within the skeletal muscle vasculature. Therefore, we sought to determine whether healthy aging is associated with changes in angiotensin II (Ang II) receptor sensitivity through measurements of leg blood flow in resting and exercising skeletal muscle. In 12 (nϭ6 young, 24Ϯ1 years; nϭ6 older, 68Ϯ3 years) healthy volunteers, we determined changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of Ang II (0.8 ng/mL of leg blood flow per minute). Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20% and 40% of the maximal work rate (WR max ). At rest, Ang II infusion decreased leg blood flow to a greater extent in older (Ϫ61Ϯ8%) subjects compared with younger subjects (Ϫ31Ϯ5%). Compared with rest, Ang II-mediated vasoconstriction (leg blood flow) during exercise was diminished in both older and younger subjects at 20% (older: Ϫ7Ϯ5%; younger: Ϫ21Ϯ2%) and 40% WR max (older: Ϫ5Ϯ4%; younger: Ϫ9Ϯ3%). These data identify a clear age-related hypersensitivity to Ang II in the resting leg, which may contribute to the recognized decrement in leg blood flow in this cohort. However, the diminished vasoconstriction to Ang II during exercise suggests that the elevation in Ang II type 1 receptor sensitivity documented at rest does not contribute significantly to the blunted exercise hyperemia experienced with advancing age. Key Words: basic science Ⅲ elderly Ⅲ blood flow regulation Ⅲ exercise Ⅲ angiotensin receptors A ngiotensin II (Ang II) acts as a potent endogenous vasoconstrictor through binding to the Ang II type 1 (AT 1 ) receptor on arteriolar vascular smooth muscle. With advancing age, there is a notable decline in plasma renin activity 1 accompanied by small decrements in circulating Ang II 2 and an increase in AT 1 receptor density. 3,4 However, the functional consequence of this age-related adaptation of the renin-angiotensin system on the peripheral circulation is not well understood. Although the pressor response to systemic Ang II infusion is elevated with age, 5 no age-specific adaptation in AT 1 receptor sensitivity has been observed with local, intra-arterial Ang II infusion in the arm. 6 Together, these studies indicate a general decline in renin-angiotensin system function with age but with uncertainty as to the impact of these changes on end-organ function and skeletal muscle hemodynamics.AT 1 receptor sensitivity to Ang II in the elderly may be especially important in the context of underlying changes in autonomic function. It is well established that elevated vasoconstrictor tone as a consequence of high sympathetic nerve activity is present in healthy, older adults, 7-9 despite a reduction in the sensitivity of postjunctional adrenergic vascular receptors. 10 This capacity for sustained sympathetic vasoconstriction in the face of reduced adrenergic responsivenes...

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