Copyright © 2004, European Society of Cardiology
Aging decreases vasoconstrictor responses of coronary resistance arterioles through endothelium-dependent mechanisms
Department of Health and Kinesiology, Texas A & M University, College Station, Texas 77843, USA
* Corresponding author. Tel.: +1 979 458 3502; fax: +1 979 847 8987. Email address: jmd{at}hlkn.tamu.edu
Objective: Aging decreases coronary blood flow and maximal reserve capacity. Impaired blood flow capacity may be related to an increased vasoconstrictor capacity of coronary resistance vessels. This study tested the hypothesis that aging increases the vasoconstrictor responsiveness of coronary arterioles isolated from myocardium of young (4 months) and old (24 months) Fischer 344 rats.
Methods: Isolated coronary arterioles were cannulated and pressurized (60 cm H2O) via hydrostatic pressure reservoirs.
Results: Contrary to our hypothesis, aging decreased responsiveness of coronary arterioles to endothelin (ET, 1 x 10–11–3 x 10–8 M), potassium chloride (KCl, 10–100 mM), and pressure-induced myogenic responses (0–140 cm H2O). Removal of the endothelium from coronary arterioles increased vasoconstriction to all agonists; however, age-related KCl vasoconstrictor response differences remained, suggesting that K+ channel activity and/or the relative contribution of specific K+ channels to maintenance of vascular smooth muscle membrane potential may change with age. Removal of the endothelium, in addition to increasing responsiveness, eliminated aging-induced differences in ET- and pressure-induced vasoconstriction. L-NAME (10–5) incubation resulted in a greater enhancement of spontaneous tone in arterioles from old rats compared to those of young rats. ETB (BQ-788, 3 x 10–8) receptor blockade eliminated the age-associated differences.
Conclusion: Collectively, these data suggest an age-associated increase in endothelial modulation of coronary resistance vessel constriction. This enhanced endothelial attenuation of coronary arteriolar constriction appears to result from increased basal release of nitric oxide. These alterations of coronary vascular reactivity may contribute to age-induced redistribution of coronary blood flow and diminished cardiac function.
KEYWORDS Aging; Coronary circulation; Microcirculation; Endothelins; Nitric oxide; Endothelial function
Time for primary review 23 days
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