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Anemia ameliorates progressive renal injury in experimental DOCA-salt hypertension
H M Lafferty1, D L Garcia, H G Rennke
1Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Insights
Reducing hematocrit levels in rats with desoxycorticosterone-salt hypertension significantly lessened kidney damage and high blood pressure. Lowering hematocrit offers a potential strategy to slow the progression of hypertensive renal disease.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Endocrinology
Background:
- Desoxycorticosterone-acetate (DOCA)-salt hypertension is a model for salt-sensitive hypertensive renal disease.
- Systemic hematocrit is implicated in vascular adaptations during hypertension.
- The specific role of hematocrit in glomerular injury within this model requires further elucidation.
Purpose of the Study:
- To investigate the impact of systemic hematocrit levels on vascular adaptations and glomerular injury in a rat model of desoxycorticosterone-salt hypertension.
- To determine if modulating hematocrit influences the progression of hypertensive renal disease.
Main Methods:
- Three groups of rats were studied: control, those receiving erythropoietin to increase hematocrit, and those made anemic via phlebotomy and a low-iron diet.
- All groups underwent uninephrectomy, desoxycorticosterone administration, and received 1% saline in drinking water.
- Systemic and glomerular capillary pressures, proteinuria, and glomerular sclerosis were assessed at 8 weeks.
Main Results:
- Control rats developed systemic and glomerular hypertension, proteinuria, and sclerosis.
- Erythropoietin administration modestly increased hematocrit and blood pressure, but significantly worsened glomerular injury.
- Hematocrit reduction through anemia significantly attenuated systemic and glomerular hypertension, proteinuria, and sclerosis.
Conclusions:
- Chronic reduction of hematocrit can limit the progression of glomerular injury in desoxycorticosterone-salt hypertension.
- Lowering hematocrit effectively ameliorates both systemic and glomerular hypertension in this model.
- Hematocrit modulation presents a potential therapeutic avenue for salt-sensitive hypertensive renal disease.
Abstract:
To explore the role of systemic hematocrit in the vascular adaptations which characterize desoxycorticosterone-salt hypertension, studies were performed in three groups of rats with uninephrectomy, desoxycorticosterone administration, and 1% saline in the drinking water. One group received recombinant human erythropoietin to increase hematocrit, and another group was subjected to phlebotomy and fed a low-iron diet to induce anemia. Control rats exhibited systemic and glomerular capillary hypertension, proteinuria, and substantial glomerular sclerosis at 8 wk. Erythropoietin modestly increased hematocrit and blood pressure and substantially aggravated glomerular capillary pressure, proteinuria, and glomerular sclerosis. In contrast, reduction of hematocrit with a low-iron diet significantly attenuated systemic and glomerular hypertension, proteinuria, and sclerosis. It was concluded that the pace of progression of glomerular injury can be limited by chronic reduction in hematocrit, which effectively ameliorates both systemic and glomerular hypertension in this model of salt-sensitive hypertensive renal disease.