Hypertension causes premature aging of endothelial function in humans.
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 microg/100 mL per minute), an endothelium-dependent vasodilator, in the presence of saline, L-arginine (1 micromol/100 mL per minute), or indomethacin (50 microg/100 mL per minute), a cyclooxygenase inhibitor, and by sodium nitroprusside (1, 2, and 4 microg/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.
Taddei
S
S
I Clinica Medica, Universiy of Pisa, Italy.
Virdis
A
A
Mattei
P
P
Ghiadoni
L
L
Fasolo
C B
CB
Sudano
I
I
Salvetti
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology; D001775:Blood Circulation / Q000187:drug effects; D004347:Drug Interactions; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D001120:Arginine; D000109:Acetylcholine