Renal injury and salt-sensitive hypertension after exposure to catecholamines

We investigated whether chronic infusion of phenylephrine could induce stru ctural and functional changes in the kidney of rats with the subsequent dev elopment of salt-sensitive hypertension. Rats were infused with phenylephri ne (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP v ariability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a n ephrectomy was performed for histological studies. Glomeruli were largely s pared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast " accumulation, and focal increases in mRNA for transforming growth factor beta by in situ hybridization, Peritubular capillaries at sites of injury h ad distorted morphology with shrinkage, rounding, and focal rarefaction, an d endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt di et. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet deve loped marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt d iet, Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r(2)=0.99) and the degree of BP lability (r(2)=0.99) duri ng the phenylephrine infusion, the amount of osteopontin expressed in the i nitial biopsy/nephrectomy (r(2)=0.74), and the final glomerular filtration rate (r(2)=0.58). These studies provide a mechanism by which a markedly ele vated sympathetic nervous system can induce salt-dependent hypertension eve n when the hyperactive sympathetic state is no longer engaged.