CIRCULATING AND CELLULAR MARKERS OF ENDOTHELIAL DYSFUNCTION WITH AGING IN RATS

xThe influence of age on endothelial functional markers was investigat ed in rats. Angiotensin I converting enzyme (ACE) activity and nitric oxide synthase (NOS) mRNA expressions were examined in the lung and ao rta of 10-, 20-, and 30-mo-old normotensive rats. These data were exte nded by the measurement of circulating endothelial cells. ACE activity was significantly decreased in plasma (P < 0.01) and lungs (P < 0.01) at 30 mo, whereas it was significantly increased in the aorta (P < 0. 001) at this age. Conversely, ACE mRNA levels decreased with age in th e lung (P < 0.05). The level of constitutive endothelial NOS (eNOS) mR NA was significantly reduced in the aorta of 30-mo-old rats (P < 0.05) , but no changes were observed in the lungs. The level of inducible NO S (iNOS) mRNA in the aorta was significantly decreased in 20-and 30-mo -old rats (P < 0.01), whereas it was significantly increased in the lu ng at 30 mo (P < 0.01). Interestingly, eNOS was expressed similar to 3 0 times more (P < 0.001) in the aorta than iNOS, whereas in the lung i t was only slightly higher than iNOS (35%; P < 0.001). Neuronal NOS mR NA expression was not modified with aging. In the aorta, guanosine 3', 5'-cyclic monophosphate concentration followed NOS expressions and sho wed a significant decrease at 30 mo (P < 0.001). An increase in the nu mber of circulating endothelial cells was observed in the oldest rats, possibly reflecting an increase in endothelial cell turnover with agi ng. The present results demonstrate that aging modifies the expression of endothelial markers implicated in the regulation of vasomotor tone . This age-dependent impairment of endothelial functions could contrib ute to the increased risk of pathological processes within the arteria l wall associated with aging.