Enhancement of Glomerular Platelet-Derived Growth Factor β-Receptor Tyrosine Phosphorylation in Hypertensive Rats and Its Inhibition by Calcium Channel Blocker

• Published in: Hypertension Research Vol. 25; no. 2; pp. 295 - 301
• Main Authors: ZHAN, Yumei, KIM, Shokei, KAWANO, Hitomi, IWAO, Hiroshi
• Format: Journal Article
• Language: English
• Published: England The Japanese Society of Hypertension 2002
• Subjects: Albuminuria; Animals; Blood Pressure - drug effects; Calcium Channel Blockers - pharmacology; Dihydropyridines - pharmacology; Genetic Predisposition to Disease; glomerulosclerosis; hypertension; Hypertension - metabolism; Hypertension - physiopathology; Kidney Glomerulus - metabolism; Male; PDGF receptor; Phosphorylation - drug effects; Proteinuria - urine; Rats; Rats, Inbred Dahl; Rats, Inbred SHR - genetics; Rats, Inbred WKY; Receptor, Platelet-Derived Growth Factor beta - metabolism; salt sensitivity; Stroke - genetics; Tyrosine - metabolism; tyrosine phosphorylation
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1291/hypres.25.295

The molecular mechanism of glomerular injury in hypertension remains to be clarified. In this study, to examine the possible role of platelet-derived growth factor (PDGF) receptors in hypertensive glomerular injury, we specifically measured glomerular PDGF receptor tyrosine phosphorylation in various models of hypertensive rats using immunoprecipitation and Western blot analysis. A high-salt diet significantly enhanced glomerular PDGF β-receptor tyrosine phosphorylation of Dahl-salt sensitive rats (DS-rats) without an increase in its protein levels, and this enhancement was associated with an elevation of blood pressure and glomerular injury. Stroke-prone spontaneously hypertensive rats (SHRSP) at hypertensive phase also had higher glomerular PDGF β-receptor tyrosine phosphorylation levels than control Wistar-Kyoto rats (WKY), while SHR did not. Thus, DS-rats and SHRSP, which are well known to represent severe glomerular injury, had the enhanced PDGF β-receptor tyrosine phosphorylation, while SHR, a hypertensive model without significant glomerular injury had no increased tyrosine phosphorylation. Treatment of DS-rats or SHRSP with benidipine, a calcium channel blocker, significantly lessened the increase in glomerular PDGF β-receptor tyrosine phosphorylation, reduction of urinary protein and albumin excretion. These results suggest that the enhanced activation of glomerular PDGF β-receptors may be responsible for the development of hypertensive glomerular injury and that the suppression of this receptor activation by a calcium channel blocker may contribute to its renal protective effects. (Hypertens Res 2002; 25: 295-301)