Enhancement of Glomerular Platelet-Derived Growth Factor β-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 ex-

Differential Induction of Protein Kinase C Isoforms at the Cardiac Hypertrophy Stage and Congestive Heart Failure Stage in Dahl Salt-Sensitive Rats

“…Salt loading (8%) significantly increased systolic blood pressure. Rats fed the lowsalt diet tended to show an increase in systolic blood pressure in a time-dependent manner, but the pressure did not reach the range of hypertension during the course of the study (24)(25)(26). Body weight was lower in rats fed the highsalt diet than in those fed the low-salt diet because rats fed the high-salt diet demonstrated appetite loss.…”

Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

“…Since hydralazine did not prevent progression to nephropathy, these effects are not attributable simply to the anti-hypertensive effects of the drugs. When Dahl salt-sensitive rats and SHRSP were treated with benidipine, glomerular platelet-derived growth factor (PDGF) β-receptor tyrosine phosphorylation was suppressed, and nephroprotective effects were observed (68). These results suggest that the effect of benidipine in suppressing factors other than glomerular pressure (e.g., TGF-β and PDGF) is also associated with its renoprotective effects.…”

“…Histopathologically, benidipine suppressed both the necrosis and apoptosis of tubules (65). In SHR with 5 / 6 nephrectomy (a model of chronic renal failure) and stroke-prone spontaneously hypertensive rats (SHRSP), benidipine suppressed the progression of renal dysfunction (67,68). In Dahl saltsensitive hypertensive rats, benidipine suppressed the progression of albuminuria and sclerotic changes in the glomeruli (50 -52, 54), and these effects of benidipine were more potent than those of amlodipine, known to exert a similar degree of anti-hypertensive activity (54, Fig.…”

Imatinib ameliorates renal morphological changes in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

“…Such elevated PDGF levels directly stimulated by the elevated arterial pressure may synergize with the elevated intrarenal ANG II levels to elicit renal functional and morphological derangements. In this regard, elevated arterial blood pressure increases PDGF expression as well as the expression of PDGF receptors in various tissues (8,9,19,26,28,36,42,43,50,68). PDGF is a 28-to 35-kDa peptide present in platelets and is secreted from vascular smooth muscle cells (VSMCs), endothelial cells, macrophages, and fibroblasts (17, 47).…”

“…MAPKs phosphorylate JNKs, which in turn results in the phosphorylation of many transcription factors, including the c-Jun component of the activator protein-1 transcription family (5). C-Jun is known to be required for PDGF-induced VSMC migration and proliferation, and JNK knockdown can attenuate cell migration and proliferation in PDGF-stimulated VSMCs (5).Although ANG II can directly activate PGDF receptors and induce PDGF expression (14,26,29,34,57), increases in arterial blood pressure directly induce PDGF expression and activate the PGDF receptor (8,19,36,37,42,43,50,54,68). Increased aortic steady-state mRNA levels of PDGF receptors were shown to be induced in DOCA salt-hypertensive rats (50).…”