The vascular endothelium in hypertension.
The vascular endothelium plays a fundamental role in the basal and dynamic regulation of the circulation. Thus, it has a crucial role in the pathogenesis of hypertension. A spectrum of vasoactive substances is synthesised in the endothelium; of these, nitric oxide (NO), prostacyclin (PGI2) and endothelin (ET)-1 are the most important. There is a continuous basal release of NO determining the tone of peripheral blood vessels. Systemic inhibition of NO synthesis or scavenging of NO through oxidative stress causes an increase in arterial blood pressure. Also, the renin-angiotensin-aldosterone system has a major role in hypertension as it has a direct vasoconstrictor effect and important interactions with oxygen free radicals and NO. Prostacyclin, in contrast to NO, does not contribute to the maintenance of basal vascular tone of conduit arteries, but its effect on platelets is most important. ET acts as the natural counterpart to endothelium-derived NO and has an arterial blood pressure-raising effect in man. Anti-hypertensive therapy lowers blood pressure and may influence these different mediators, thus influencing endothelial function. In summary, due to its position between the blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both victim and offender in arterial hypertension. The delicate balance of endothelium-derived factors is disturbed in hypertension. Specific anti-hypertensive and anti-oxidant treatment is able to restore this balance.
Spieker
L E
LE
Cardiovascular Centre, Cardiology, Dep. of Internal Medicine, University Hospital, 8091 Zürich, Switzerland.
Flammer
A J
AJ
Lüscher
T F
TF
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011453:Prostaglandins / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001685:Biological Factors; D002121:Calcium Channel Blockers; D019332:Endothelin-1; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide