title: Enhancement of glomerular platelet-derived growth factor beta-receptor tyrosine phosphorylation in hypertensive rats and its inhibition by calcium channel blocker.
abstract: 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 beta-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 beta-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 beta-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 beta-receptor tyrosine phosphorylation, reduction of urinary protein and albumin excretion. These results suggest that the enhanced activation of glomerular PDGF beta-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.
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhan
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kawano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000419:Albuminuria; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D020521:Stroke / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014443:Tyrosine; C061004:benidipine; D020797:Receptor, Platelet-Derived Growth Factor beta