Renal cortical vasoconstriction contributes to development of salt-sensitive hypertension after angiotensin II exposure

Rats that are administered angiotensin II (AngII) for 2 wk develop persiste nt salt-sensitive hypertension, which can be prevented by the immunosuppres sor mycophenolate mofetil (MMF) given during the AngII infusion. This study examined the contribution of glomerular hemodynamics (GFR dynamics) in the post-AngII hypertensive response to a high-salt diet (HSD) and the effect of MMF treatment. During AngII administration, rats developed severe hypert ension (systolic BP [SBP], 185 +/- 3.9 mmHg), proteinuria, afferent and eff erent vasoconstriction, and glomerular hypertension. Rats that received Ang II+MMF showed similar responses to AngII; however, they developed lower pro teinuria (P < 0.05). At 2 wk, AngII was withdrawn and SBP returned toward n ormal. Rats were then placed on an HSD (4% NaCl), resulting in a progressiv e increase in SBP (155 <plus/minus> .2 mmHg at week 1 and 163 +/- 4.5 mmHg at week 5). GFR dynamic alterations persisted after AngII was stopped, i.e. , afferent and efferent vasoconstriction, decreased glomerular plasma flow and single-nephron GFR, and lower ultrafiltration coefficient. These change s correlated with the thickening of the afferent arteriole and with focal t ubulointerstitial injury. In the AngII+MMF group, SBP remained unchanged th roughout the HSD period (146 +/- 2.3 mmHg at week 1 and 148 +/- 4.4 mmHg at week 5) in association with less afferent arteriolar thickening and tubulo interstitial injury. Single-nephron GFR, glomerular plasma flow, efferent r esistance, and ultrafiltration coefficient returned to normal with a signif icant reduction in afferent resistance. These results suggest a critical ro le of cortical vasoconstriction in salt-sensitive hypertension. The MMF-ind uced prevention of these changes suggests that immune mechanisms are involv ed in the vasoconstrictive response.