Vasodilatory responsiveness to adenosine triphosphate in ageing humans

Abstract

Endothelium-dependent vasodilatation is reduced with advancing age in humans, as evidenced by blunted vasodilator responsiveness to acetylcholine (ACh). Circulating adenosine triphosphate (ATP) has been implicated in the control of skeletal muscle vascular tone during mismatches in oxygen delivery and demand (e.g. exercise) via binding to purinergic receptors (P 2Y ) on the endothelium evoking subsequent vasodilatation, and ageing is typically associated with reductions in muscle blood flow under such conditions. Therefore, we tested the hypothesis that ATP-mediated vasodilatation is impaired with age in healthy humans. We measured forearm blood flow (venous occlusion plethysmography) and calculated vascular conductance (FVC) responses to local intra-arterial infusions of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA) infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was significantly impaired in older compared with young adults (262 ± 71% vs. 618 ± 97%; P < 0.05), and this difference was abolished during AA infusion (510 ± 82% vs. 556 ± 71%; not significant, NS). In contrast, peak FVC responses were not different between older and young adults to either ATP (675 ± 105% vs. 734 ± 126%) or SNP (1116 ± 111% vs. 1138 ± 148%) and AA infusion did not alter these responses in either age group (both NS). In another group of six young and six older adults, we determined whether vasodilator responses to adenosine and ATP were influenced by P 1 -receptor blockade via aminophylline. The peak FVC responses to adenosine were not different in young (350 ± 65%) versus older adults (360 ± 80%), and aminophylline blunted these responses by ∼50% in both groups. The peak FVC responses to ATP were again not different in young and older adults, and aminophylline did not impact the vasodilatation in either group. Thus, in contrast to the observed impairments in ACh responses, the vasodilatory response to exogenous ATP is not reduced with age in healthy humans. Further, our data also indicate that adenosine mediated vasodilatation is not reduced with age, and that ATP-mediated vasodilatation is independent of P 1 -receptor stimulation in both young and older adults.

Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress

“…Ϫ1 followed by a 2.5 mg/min maintenance infusion) was used as a potent antioxidant (5,18,19,39,40). All drug infusions were infused locally and adjusted for FAV to 1) directly assess changes within the microvasculature of the resting forearm, 2) minimize systemic blood pressure changes and activation of counterregulatory systems, and 3) normalize the concentrations of each drug across conditions and control for differences in forearm size between groups.…”

Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins

“…ATP was confirmed sterile and free of fungus/endotoxin with a standard microbiology report (JCB-Analytical Research Labs, Wichita, KS) before use (19,20).…”

“…Forearm blood flow (FBF) was measured via venous occlusion plethysmography using mercury-in-salistic strain gauges (17,19). A pediatric blood pressure cuff was placed around the wrist of the experimental arm and inflated to suprasystolic pressure (ϳ200 mmHg) to arrest the hand circulation.…”

“…In protocol 1, the P 2Y-receptor agonist ATP (Sigma A7699) was infused at 1.25, 2.5, and 5 g·dl FAV Ϫ1 ·min Ϫ1 for 4 min each (19,20). ATP was confirmed sterile and free of fungus/endotoxin with a standard microbiology report (JCB-Analytical Research Labs, Wichita, KS) before use (19,20).…”

“…Total FAV was calculated from regional analysis of the experimental forearm (from the proximal to distal radioulnar joint) from whole body DEXA scans with QDR series software for normalization of the dose of ATP (19). Body mass index was calculated as body weight (kg) divided by height (meters) squared.…”