Overview of Physiology, Vascular Biology, and Mechanisms of Hypertension

BACKGROUND: Our understanding of the process leading to hypertension is allowing us to adopt principles of therapy that may be more beneficial for patients. OBJECTIVES: To review the physiology, vascular biology, and mechanisms of hypertension. SUMMARY: Hypertension, particularly in high-risk patients, is a result of loss of balance and the absence of the ability to vasodilate normally. The interaction between the endothelial cell and the smooth muscle cell is very important in this process. The endothelium is a group of cells that produce compounds that are important in regulating vascular homeostasis by elaborating factors such as angiotensin II, nitric oxide (NO), endothelin, and prostaglandins. Specifically, NO is found in endothelial cells responsible for smooth muscle relaxation. Gaseous NO diffuses across the endothelial cell and into the underlying smooth muscle cell, where it stimulates the pathway of guanylate cyclase to produce vasorelaxation. Normal endothelium maintains vascular tone and blood viscosity, prevents abnormal blood clotting and bleeding, limits inflammation of the vasculature, and suppresses smooth muscle cell proliferation. Abnormal endothelium causes increased inflammation and hypertrophy of the smooth muscle cells, promotes thrombosis and vasoconstriction, and creates a situation ripe for establishment and rapid growth of atherosclerotic plaques. Endothelial dysfunction also predicts poor outcome in patients with non insulin-dependent diabetes mellitus and may worsen insulin resistance, increase vascular reactivity, and encourage macrovascular disease. CONCLUSIONS: Understanding endothelial vasculature will be imperative as researchers develop newer compounds that may enhance NO formation within the vasculature.