Furosemide treatment, angiotensin II, and renal growth and development in the rat

Diuretics are commonly used to treat a variety of conditions, including progressive nephropathies, cardiovascular, and pulmonary diseases. Such treatment stimulates the production of angiotensin II, an important mediator of renal growth which may accelerate progressive glomerulosclerosis. To further study the effects of diuretic treatment on normal renal growth and development, weanling male Munich-Wistar rats received no drug, enalapril, furosemide, or both drugs for 6 wk; morphometric studies were then performed using standard light and electron microscopic techniques. Plasma renin activity was elevated by furosemide treatment. Cortical tubular growth was stimulated in rats receiving furosemide or both drugs; enalapril did not affect cortical tubular growth when compared with untreated animals. Glomerular volume was increased in furosemide-treated animals, primarily due to an increase in the proportion of mesangial cells, whereas enalapril decreased glomerular volume. Furosemide also increased the filtration surface area per glomerulus whereas enalapril decreased it. Concurrent enalapril treatment blocked the furosemide-induced changes in filtration surface area as well as attenuating overall glomerular and mesangial growth. Glomerular changes correlated with plasma renin activity. Furosemide stimulated glomerular growth, especially of mesangial cells, probably via stimulation of AngII production. Given the relationship of mesangial cell growth and progressive renal disease, diuretic therapy could thus accelerate glomerulosclerosis. Cortical tubular growth also increased with furosemide; however, enalapril had no effect, so factors besides angiotensin II appeared to modulate tubulointerstitial growth in these animals.