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A rationale for treatment of endothelial dysfunction in hypertension.
- Source :
-
Journal of hypertension. Supplement : official journal of the International Society of Hypertension [J Hypertens Suppl] 1999 Feb; Vol. 17 (1), pp. S25-35. - Publication Year :
- 1999
-
Abstract
- Strategically located between the circulating blood and the vascular smooth muscle, endothelial cells release numerous vasoactive substances that regulate the function of vascular smooth muscle and circulating blood cells. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide (NO) and, independent of the former, endothelium-derived hyperpolarizing factor. In particular, NO inhibits cellular growth and migration. In concert with prostacyclin, NO exerts potent antiatherogenic and thromboresistant properties by preventing platelet aggregation and cell adhesion. These effects are counterbalanced by vasoconstrictors, angiotensin II and endothelin-1, both of which exert prothrombotic and growth-promoting properties. In hypertension, elevated blood pressure transmits into cardiovascular disease by causing endothelial dysfunction. Hence, modern therapeutic strategies in human hypertension focus on preserving or restoring endothelial integrity. Calcium antagonists counteract angiotensin II and endothelin-1 at the level of vascular smooth muscle by reducing the inflow of Ca2+ and facilitating the vasodilator effects of NO. Besides inhibiting the renin-angiotensin system, angiotensin-converting enzyme inhibitors diminish the inactivation of bradykinin, leading to an augmented release of NO. Newly developed vasopeptidase inhibitors induce potent antihypertensive effects in low-, normal-, and high-renin models of hypertension, not only because of the decreased breakdown of natriuretic peptides, but also because of the inhibition of endothelin-1 generation. Furthermore, experimental studies suggest that endothelin antagonists effectively lower blood pressure and prevent target-organ damage in salt-sensitive forms of hypertension. Further clinical studies are already underway to examine whether restoring endothelial dysfunction results in a clinical benefit in hypertension.
- Subjects :
- Blood Pressure drug effects
Cell Division drug effects
Drug Therapy, Combination
Endothelin-1 antagonists & inhibitors
Endothelin-1 metabolism
Endothelium, Vascular drug effects
Endothelium, Vascular pathology
Humans
Hypertension metabolism
Hypertension physiopathology
Nitric Oxide antagonists & inhibitors
Nitric Oxide metabolism
Vasodilation drug effects
Angiotensin-Converting Enzyme Inhibitors therapeutic use
Antihypertensive Agents therapeutic use
Calcium Channel Blockers therapeutic use
Endothelium, Vascular metabolism
Hypertension drug therapy
Vasodilator Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0952-1178
- Volume :
- 17
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hypertension. Supplement : official journal of the International Society of Hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 10340841