Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients.
Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to test whether antihypertensive treatment with the calcium antagonist lacidipine can improve endothelium-dependent vasodilation in essential hypertensive patients. In 12 normotensive subjects (mean age, 47.8+/-8.6 years; blood pressure, 118.6+/-4.2/76.7+/-3.9 mm Hg) and 19 hypertensive patients (mean age, 49.4+/-10.2 years; blood pressure; 153.5+/-13.3/101.3+/-6.4 mm Hg), we studied forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute) and bradykinin (5, 15, and 50 ng/100 mL per minute), two endothelium-dependent vasodilators that act through different receptors and signal transduction pathways, and sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. In essential hypertensive patients, vascular reactivity was repeated during prolonged (8 weeks of oral treatment at 6 mg/d) lacidipine administration and 2 weeks after withdrawal of chronic (32-week) treatment. Hypertensive patients showed significantly (P<.01) blunted vasodilation in response to acetylcholine (vascular resistance, 31.5+/-4.9 to 7.6+/-2.4 SU) and bradykinin (vascular resistance, 32.3+/-5.8 to 8.5+/-3.0 SU) compared with control subjects (vascular resistance: acetylcholine, 24.3+/-3.9 to 3.7+/-1.2 SU; bradykinin, 24.7+/-0.4 to 4.1+/-1.3 SU), whereas the response to sodium nitroprusside was similar. After either 8 or 32 weeks of lacidipine treatment, the vasodilation in response to acetylcholine (30.6+/-7.7 to 5.7+/-1.5 and 34.3+/-6.6 to 5.9+/-1.9 SU, respectively) and bradykinin (31.3+/-7.2 to 6.4+/-1.6 and 33.7+/-5.4 to 6.1+/-1.5 SU, respectively), but not to sodium nitroprusside, proved to be significantly (P<.05) increased compared with baseline. In essential hypertensive patients, oral treatment with lacidipine increased forearm vasodilation in response to acetylcholine and bradykinin, suggesting that this drug can improve endothelial function in patients with essential hypertension.
Taddei
S
S
I Clinica Medica, University of Pisa, Italy.
Virdis
A
A
Ghiadoni
L
L
Uleri
S
S
Magagna
A
A
Salvetti
A
A
D000109:Acetylcholine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009599:Nitroprusside; C060285:lacidipine; D000109:Acetylcholine; D001920:Bradykinin