Increased Renal Vascular Endothelial Growth Factor and Angiopoietins by Angiotensin II Infusion Is Mediated by Both AT1 and AT2 Receptors

Abstract

Abstract.A link between angiotensin II and cell proliferation has previously been reported. However, there remains controversy as to the role of the individual angiotensin II receptor subtypes in mediating these effects and their link to angiogenic cytokines and their receptors. Male Sprague-Dawley rats were infused with either angiotensin II or vehicle for 14 d at a dose of 58.3 ng/min. Angiotensin II-infused rats received no treatment, an AT 1 receptor antagonist valsartan (30 mg/kg per d), or an AT 2 receptor antagonist PD123319 (830 ng/min).

Targeted Deletion of Angiotensin II Type 1A Receptor Does not Protect Mice from Progressive Nephropathy of Overload Proteinuria

“…The similarity of the beneficial effect of ACE inhibitors and AT 1 receptor antagonists in experimental models and clinical studies would further support the notion that AT 2 receptor stimulation does not contribute to the pathogenesis of renal disease. Other recent studies have challenged the view of AT 2 as a "protective" receptor (40) and provided evidence that the growth stimulatory and proinflammatory effects of Ang II also may be transduced by AT 2 , which induces glomerular cell proliferation and monocyte/macrophage infiltration, albeit to a lower extent than AT 1 receptor (41,42). This observation together with the evidence of AT 2 upregulation in protein-overload proteinuria (43) would offer the rationale for studies with specific AT 2 antagonists.…”

Redox Control of Renal Function and Hypertension

“…Ang II-induced hypertrophy of cultured murine proximal tubular cells was shown to be mediated by endogenous TGF-␤ (368). Ang II also stimulates VEGF expression and PTC modulation, both via transcriptional and translational mechanisms (65,272). The translational increase in VEGF expression is brief (detected at 5 min and lasts 45 min) and is mediated by activation of PI3-kinase and its downstream target Akt.…”

From the Periphery of the Glomerular Capillary Wall Toward the Center of Disease

“…In cultured podocytes, VEGF expression can be stimulated by high glucose concentrations (91), by TGF-␤1 (91,92), and by ANG II acting via AT 1 and AT 2 receptors (93,94). The gene expression of VEGF is also stimulated by a transcription factor called hypoxia-inducible factor-1 (95).…”