399 VACCINATION AGAINST THE ANGIOTENSIN II TYPE 1 RECEPTOR PREVENTS L-NAME-INDUCED NEPHROPATHY IN SHR

Objectives: Previous studies have shown that renin–angiotensin (Ang) system vaccines may be effective for the treatment of hypertension, but their efficacy for the prevention of renal disease is unclear. The aim of this study was to examine the effects of an Ang II type 1 (AT1) receptor vaccine on blood pressure (BP) and renal injury in the L-NAME nephropathy model. Methods: Male spontaneously hypertensive rats (SHRs) were divided into six groups and treated transiently with three injections of vehicle or AT1 receptor vaccine (0.1 mg) at age 4, 6 and 8 weeks, or continuously with candesartan cilexetil (0.1 mg/kg/day) or hydralazine hydrochloride (5 mg/kg/day), then administered NG-nitro-Larginine methyl ester (L-NAME) from age 18 to 21 weeks to induce renal injury. Results: Vaccination against the AT1 receptor caused a significant increase in AT1 receptor titers, and a sustained decrease in BP. L-NAME treatment resulted in a marked increase in proteinuria in the control groups, which was markedly suppressed in the AT1 vaccine-treated group, and glomerular injury scores were also significantly decreased. Real-time RT-PCR and immunofluorescence studies revealed increased renin mRNA, and increased glomerular expression of nephrin. Comparable results were seen in rats treated continuously with the ARB candesartan, but not with hydralazine. The elevated titers and hypotensive effect continued for approximately 6 months after the final vaccination. Conclusion: These results suggest that transient AT1 vaccination is as effective as continuous treatment with ARB, not only for the attenuation of hypertension, but also for the prevention of L-NAME-induced nephropathy in SHR.