HYPERTENSION CAUSES PREMATURE AGING OF ENDOTHELIAL FUNCTION IN HUMANS

We designed the present study to evaluate whether in normotensive subj ects and hypertensive patients aging causes endothelial dysfunction by a defect in the L-arginine-nitric oxide pathway or production of cycl ooxygenase-dependent vasoconstrictors. In 43 normotensive subjects and 47 essential hypertensive patients, we evaluated forearm blood flow ( strain-gauge plethysmography) modifications evoked by intrabrachial ac etylcholine (0.15, 0.45, 1.5, 4.5, and 15 mu g/100 mL per minute), an endothelium-dependent vasodilator, in the presence of saline, L-argini ne (1 mu mol/100 mL per minute), or indomethacin (50 mu g/100 mt per m inute), a cyclooxygenase inhibitor, and by sodium nitroprusside (1, 2, and 4 mu g/100 mL per minute), an endothelium-independent vasodilator . Vasodilation to acetylcholine was lower (P<.01) in essential hyperte nsive patients than normotensive control subjects, and in both groups, it declined with advancing age. In normotensive subjects older than 3 0 years, L-arginine potentiated the response to acetylcholine in paral lel with increasing age, whereas indomethacin increased the vasodilati on to acetylcholine only in the oldest group (>60 years). In younger h ypertensive patients (<30 years), L-arginine but not indomethacin pote ntiated the response to acetylcholine. In adult patients (31 to 45 yea rs), L-arginine still potentiated the vasodilation to acetylcholine, a nd indomethacin began to show some effect. In the oldest patients (46 to 60 and >60 years), L-arginine was no longer effective, and indometh acin exerted a potentiating action that was positively related to adva ncing age. In normotensive and hypertensive humans, similar mechanisms , including dysfunction of the nitric oxide pathway and production of cyclooxygenase-dependent vasoconstrictors, cause age-related impairmen t of endothelium-dependent vasodilation, and only their earlier appear ance characterizes hypertensive disease. Thus, the endothelial dysfunc tion that occurs in hypertension seems to represent an accelerated for m of dysfunction that occurs in aging.