Interactions of the endothelium and mesangium in glomerular injury

Glomerular mesangial and endothelial cells have key roles in the regulation of glomerular blood flow, both under normal circumstances and in pathologic states. The anatomic structure of the glomerulus is such that the endothelial and mesangial cells are in close proximity to each other and consequently may communicate through a number of cellular mediators. Vasodilatory substances, such as prostacyclin and endothelium-derived relaxing factor, and vasoconstrictive substances, such as endothelin, are released by endothelial cells and can interact with mesangial cells to affect glomerular blood flow. The ability of plasma macromolecules to enter and circulate through the mesangium may play an important role in the development of glomerular injury. Angiotensin II has been shown to increase the uptake and decrease the rate of disappearance of certain macromolecules in the mesangium; this action is blocked, at least partially, by angiotensin II receptor antagonists and by calcium channel blockers. Experimental studies have suggested that angiotensin converting enzyme inhibitors and calcium channel blockers may prevent or arrest progression of renal injury. Angiotensin converting enzyme inhibitors may have a beneficial effect by decreasing intraglomerular pressure through inhibition of angiotensin II predominant constriction of the glomerular efferent arteriole and possibly by decreasing mesangial trafficking of macromolecules. Calcium channel blockers may have beneficial effects on intracellular events that occur because of injury of either endothelial or mesangial cells.