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Systemic and renovascular hypertension
B Jackson1, L Franze, M Whitty
1University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Abstract:
To ascertain the contribution of systemic hypertension in the progression of renal failure, we have studied the effects of pharmacological treatment of hypertension in rats with the remnant kidney model of renal insufficiency, streptozotocin diabetes, or nephrotoxic serum nephritis. Treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril lowered systemic blood pressure in the remnant kidney and diabetic animals, but did not lower blood pressure in rats with nephrotoxic serum nephritis. Proteinuria was reduced in all three models, and creatinine clearance improved in the remnant kidney and diabetic animals, when compared with untreated controls. In the remnant kidney and diabetic models systemic blood pressure was lowered to a similar degree by treatments with a calcium blocker, with no improvement in either proteinuria, or glomerular filtration rate. Further studies of the long-term effects of enalapril have been undertaken in rats with the two kidney one clip model of hypertension. Rats treated with enalapril had a lower blood pressure and improved survival over one year of treatment, compared with untreated rats. After 1 year of treatment however the clipped kidney was small and fibrotic, and non functional. Following withdrawal of enalapril therapy there was no functional improvement of the clipped kidney. The possibility that ACE inhibitors have a specific intra-renal effect reducing the rate of progression of renal disease now needs confirmation in human studies. In renovascular hypertension however, intra-renal changes induced by ACE inhibitors may cause irreversible renal damage.
Insights
Angiotensin converting enzyme (ACE) inhibitors like enalapril reduced blood pressure and improved kidney function in rat models of renal failure. However, long-term use may cause irreversible kidney damage in certain hypertension types.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Medicine
Background:
- Systemic hypertension is a significant factor in chronic kidney disease progression.
- Understanding the renal effects of antihypertensive treatments is crucial for managing kidney failure.
Purpose of the Study:
- To investigate the impact of angiotensin converting enzyme (ACE) inhibitor enalapril on renal failure progression in rat models.
- To compare the effects of ACE inhibitors with calcium channel blockers on renal function and proteinuria.
Main Methods:
- Utilized rat models: remnant kidney, streptozotocin-induced diabetes, nephrotoxic serum nephritis, and two-kidney one-clip hypertension.
- Administered enalapril (ACE inhibitor) and calcium channel blockers, monitoring blood pressure, proteinuria, and creatinine clearance.
- Assessed long-term effects of enalapril on renal morphology and function, including survival rates.
Main Results:
- Enalapril lowered blood pressure in remnant kidney and diabetic rats, reducing proteinuria and improving creatinine clearance.
- Calcium channel blockers lowered blood pressure similarly but did not improve proteinuria or glomerular filtration rate.
- Long-term enalapril treatment in renovascular hypertension models improved survival but led to fibrotic, non-functional kidneys, with no recovery after drug withdrawal.
Conclusions:
- ACE inhibitors demonstrate potential intra-renal benefits in slowing renal disease progression, warranting human studies.
- Irreversible renal damage may occur with ACE inhibitors in specific conditions like renovascular hypertension.