Cultured Glomerular Mesangial Cells Contain Renin

Abstract

Glomerular mesangial cells are contractile cells responsive to a variety of vasoactive substances. In addition, they are capable of synthesizing prostaglandins and renin-like enzyme(s) (RLE). We examined the identity of the RLE in cultured rat mesangial cells utilizing specific antibody raised to pure renal renin. Unlike cathepsin D, RLE is active at pH 7.4. One million mesangial cells contain 174 +/- 53 pg ANG I/h RLE intracellularly (ANG I, angiotensin I; n = 26). As evidenced by inhibition by renin-specific antibody, 52 +/- 3% RLE is due to immunoreactive renin. Mesangial immunoreactive renin activity is influenced by beta-adrenergic stimulation and increased extracellular calcium. Exposure to 1 microM isoproterenol at 37 degrees C for 1 h resulted in 103 +/- 53% increase in intracellular activity, i.e., 56 +/- 8 to 102 +/- 15 pg ANG I/h/10(6) cells (p less than 0.05, n = 7). Addition of calcium to culture media for 1 h resulted in an increase in intracellular renin activity. Addition of 1 mM (final concentration) calcium resulted in a ninefold increase in mesangial renin activity from 21 +/- 8 to 185 +/- 10 pg ANG I/h/10(5) cells (n = 4, p less than 0.001). Similarly, 4 mM calcium resulted in a sevenfold increase (n = 4, p less than 0.001). Thus, mesangial cells synthesize renin, which can be regulated by beta-adrenergic receptors and extracellular calcium. This intracellular renin may play an important role in the local regulation of contractile response and glomerular dynamics.