Table 1.
Studies ascertaining effects of V2 and/or V1a agonism or antagonism on CKD progression
| Study * | Drug | Class | Animal model | Treatment duration | Outcome |
|---|---|---|---|---|---|
| Okada 1994 | OPC-21268 or OPC-31260 or both | V1aRA, V2RA | DOCA-salt and adryamycin treated rats | 2–6 wks | All reduced BP rise, V1aRA/V2RA ameliorated histology |
| Okada 1995 | OPC-21268 or OPC-31260 or both | V1aRA, V2RA | Uninephrectomized DOCA-salt hypertensive rats | 6–10 wks (starting at surgery or 4 wks later) | V2RA or V1aRA/V2RA reduced BP rise |
| Okada 1995 | OPC-21268 or OPC-31260 or both | V1aRA, V2RA | 5/6 nephrectomized spontaneously hypertensive rats | V1aRA or V1aRA/V2RA reduced BP rise, proteinuria and arteriolosclerosis | |
| Okada 1996 | OPC-21268 or OPC-31260 or both | V1aRA, V2RA | Adryamycin treated rats | 5–7 wks | All reduced proteinuria and histological alterations |
| Kurihara 1996 | OPC-21268 | V1aRA | Uninephrectomized spontaneously hypercholesterolemic rats | 9 wks | V1aRA reduced BP and glomerular sclerosis, and improved renal function |
| Bouby 1999 | DDAVP | V2R agonist | Brattleboro 5/6 nephrectomized rats | 13 weeks | DDAVP increased proteinuria and worsened renal function |
| Naito 2001 | DDAVP and VP-343 | V2R agonist, V2RA | Sprague-Dawley rats | 15 days (VP-343 given only on days 5– 15) | DDAVP induced and VP- 343 prevented hypertrophy, tubular dilatation, interstitial infiltration |
| Fernandes 2002 | DDAVP or SR- 121463 | V2R agonist, V2RA | Uninephrectomized DOCA-salt hypertensive rats | 8 weeks | DDAVP worsened hypertension, albuminuria and histology |
| Bardoux 2003 | SR-121463 | V2RA | Streptozotocin-induced diabetes mellitus | 9 wks | V2RA prevented rise in albuminuria |
| Windt 2006 | YM-218 | V1aRA | 5/6 nephrectomized rats | 8 wks (starting 2 wks post surgery) | V1RA reduced proteinuria and glomerular sclerosis |
| Windt 2006 | YM-218 | V1aRA | 5/6 nephrectomized rats | 4 wks (starting 6 wks post surgery) | No effect |
| Okada 2009 | Tolvaptan | V2RA | Puromycin aminonucleoside nephrosis | 10 days | V2RA reduced proteinuria and kidney weight and improved renal function |
| Perico 2009 | RWJ-676070 | V1a/V2 RA | 5/6 nephrectomized rats | 39 days (starting 3 wks after surgery) | V1a/V2 RA reduced BP rise, proteinuria and glomerular sclerosis |
*
References available on request