Angiotensin II infusion ameliorates the early phase of a mesangioproliferative glomerulonephritis1 (original) (raw)

2002, Kidney International

Angiotensin II infusion ameliorates the early phase of a mesanexperimental and clinical studies have documented a gioproliferative glomerulonephritis. strong nephroprotective effect of antihypertensive ther-Background. Inhibition of the renin-angiotensin system slows apy using angiotensin-converting enzyme (ACE) inhibithe progression of chronic renal disease. tors [1, 2]. Furthermore, there is clear evidence that ACE Methods. To test whether angiotensin II (Ang II) infusion aggravates or ameliorates an acute glomerulonephritis, the inhibitors show beneficial effects that go beyond their peptide was infused (200 ng/min by osmotic minipump) in rats blood pressure lowering effect. However, the mechawith an anti-thymocyte antibody-induced glomerulonephritis nisms of action of ACE inhibitors remain incompletely (ATS). understood. Both experimental and clinical studies re-Results. Ang II significantly increased blood pressure. Following injection of the antibody, similar glomerular binding of vealed that angiotensin II (Ang II) plays a central role rabbit IgG and rat complement C3 was detected in ATS and in the progression of renal disease [3]. The mechanisms Ang IIϩATS rats, indicating no differences in delivery and of Ang II-induced kidney damage are generally attribbinding of the antibody. Ang II infusion, however, induced a uted to direct vasoconstriction, growth promoting and significant reduction in glomerular monocyte infiltration, cell proliferation and matrix expansion in nephritic rats compared profibrotic effects. We and others have characterized the to rats with nephritis without Ang II. The antiproliferative model of anti-Thy-1 induced glomerulonephritis [4-6]. effect of Ang II was inhibited by the Ang II type 1 (AT1) re-The injection of a rabbit anti-rat thymocyte serum inceptor blocker irbesartan, but not by the AT2 receptor blocker duces mesangiolysis, followed by monocyte infiltration PD 123319, indicating that this effect was likely transduced by AT1 receptors. Norepinephrine infusion (600 ng/min) pro-as well as proliferation and matrix expansion. It has been duced a similar degree of hypertension, but did not affect demonstrated that blockade of the renin-angiotensin sysglomerular proliferation in nephritic rats. Ang II induced the tem with ACE inhibitors or Ang II type 1 (AT1) receptor glomerular expression of the cell cycle inhibitor p27 KIP1 and of blockers ameliorates the pathologic changes of the early transforming growth factor-␤ (TGF-␤) and inhibited expression of monocyte chemotactic protein 1 (MCP-1). phase of the anti-thymocyte antibody-induced glomeru-Conclusion. Ang II surprisingly ameliorates glomerular monolonephritis (ATS) [7, 8]. In addition, we recently found cyte infiltration, proliferation and matrix expansion in ATS that induction of ATS in rats with renovascular hypertennephritis. Ang II-mediated induction of cyclin kinase inhibitors sion aggravated the glomerular damage of ATS in the and TGF-␤ may contribute to the protection of the glomerulus from inflammatory injury by inducing cell cycle arrest and nonclipped kidney [9]. Therefore, we were interested in attenuating activation of local and recruited cells. Alternafurther dissecting the obviously deleterious effects of tively, Ang II might protect the kidney at least in part by less Ang II on the course of ATS. Surprisingly, we discovered inflow of disease activators due to reduction of renal blood that infusion of Ang II led to a marked suppression flow. Therefore, activation of the renin-angiotensin system may have protective effects in certain pathophysiological situations.