Changes in vascular reactivity of coronary resistance arterioles with aging.

摘要

Aging decreases maximal coronary blood flow and coronary reserve capacity. Because the resistance vasculature contributes importantly to control of coronary blood flow, the purpose of this study was to determine the effects of age on vasoreactivity of coronary resistance arterioles. Coronary arterioles (150μm) from young (4 months) and old (24 months) Fischer 344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Diameter changes were determined in response to graded increases in intraluminal flow, ACh (10 −9 to 10−4M), sodium nitroprusside (SNP, 10−10–10−4 M), endothelin (ET, 1 × 10−11M–3 × 10−8 M), potassium chloride (KCl, 10mM–100mM), and pressure (0–140cm H₂O). Aging substantially decreased flow-induced dilation and reduced sensitivity to ACh. NG-nitro-L-arginine methyl ester (L-NAME, 10−5) abolished flow- and ACh-induced dilations of arterioles from young and old rats. Inhibition of COX-1 with indomethacin had no effect on the flow-induced dilation seen in arterioles from young rats, but partially inhibited the response in aged rats. Indomethacin eliminated ACh-induced dilation in arterioles from young rats, and partially inhibited the vasodilation in arterioles from old rats. These results suggest that age reduces NO-dependent dilation, and alters the balance between NOS and COX-1 mechanisms of endothelial-dependent function.; Aging decreased responsiveness of coronary arterioles to endothelin (ET, 1 × 10−11M–3 × 10 −8M), potassium chloride (KCl, 10mM–100mM), and pressure (0–140cm H₂O). Removal of the endothelium from coronary arterioles increased vasoconstriction to KCl, ET, and pressure changes, and eliminated aging-induced differences in ET- and pressure-induced vasoconstriction. Although endothelial removal augmented constriction to KCl, age-related KCl vasoconstrictor response differences remained, suggesting that K+ channel activity and/or contribution of K+ channels to maintenance of vascular smooth muscle membrane potential may change with age. L-NAME produced greater enhancement of spontaneous tone and constriction to ET in arterioles from aged rats compared to those of young rats. 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.