Working under pressure: the vascular endothelium in arterial hypertension.
The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyte-adhesion to the vascular wall. Besides its blood pressure rising effect also in man, ET induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by genetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both target and mediator of arterial hypertension. Oxidative stress plays an important role in the pathogenesis of hypertension. Superoxide anions, ie, oxygen radicals produced in part by angiotensin II-activated NAD(P)H oxidase, can scavenge NO to form peroxynitrite, which can nitrosylate membrane proteins and oxidize lipids. Another source of superoxide is cyclooxygenase. Paradoxically, dysfunctional endothelial NO synthase may also be a source of superoxide anions. Surprisingly and in contrast to animal experiments, not all antihypertensive treatments consistently restore endothelium-dependent vasodilation in patients with arterial hypertension. Endothelial dysfunction in hypertension is crucial both for the development of the disease process in the vasculature and an important therapeutic target.
Spieker
L E
LE
Cardiology, University Hospital, Zürich, Switzerland.
Noll
G
G
Ruschitzka
F T
FT
Maier
W
W
Lüscher
T F
TF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase