Hypertension Causes Premature Aging of Endothelial Function in Humans

Abstract

We designed the present study to evaluate whether in normotensive subjects and hypertensive patients aging causes endothelial dysfunction by a defect in the L-arginine–nitric oxide pathway or production of cyclooxygenase-dependent vasoconstrictors. In 43 normotensive subjects and 47 essential hypertensive patients, we evaluated forearm blood flow (strain-gauge plethysmography) modifications evoked by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL per minute), an endothelium-dependent vasodilator, in the presence of saline, l -arginine (1 μmol/100 mL per minute), or indomethacin (50 μg/100 mL per minute), a cyclooxygenase inhibitor, and by sodium nitroprusside (1, 2, and 4 μg/100 mL per minute), an endothelium-independent vasodilator. Vasodilation to acetylcholine was lower ( P <.01) in essential hypertensive patients than normotensive control subjects, and in both groups, it declined with advancing age. In normotensive subjects older than 30 years, l -arginine potentiated the response to acetylcholine in parallel with increasing age, whereas indomethacin increased the vasodilation to acetylcholine only in the oldest group (>60 years). In younger hypertensive patients (<30 years), l -arginine but not indomethacin potentiated the response to acetylcholine. In adult patients (31 to 45 years), l -arginine still potentiated the vasodilation to acetylcholine, and indomethacin began to show some effect. In the oldest patients (46 to 60 and >60 years), l -arginine was no longer effective, and indomethacin exerted a potentiating action that was positively related to advancing age. In normotensive and hypertensive humans, similar mechanisms, including dysfunction of the nitric oxide pathway and production of cyclooxygenase-dependent vasoconstrictors, cause age-related impairment of endothelium-dependent vasodilation, and only their earlier appearance characterizes hypertensive disease. Thus, the endothelial dysfunction that occurs in hypertension seems to represent an accelerated form of dysfunction that occurs in aging.