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Title: Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.
Austin Authors: Fabris, Bruno;Jackson, B ;Johnston, Colin I
Affiliation: University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Apr-1991
Publication information: Hypertension; 17(4): 497-503
Abstract: To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.
Gov't Doc #: 1826492
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology
Bicyclo Compounds.antagonists & inhibitors.pharmacology
Blood Glucose.analysis
Blood Pressure.drug effects
Diabetes Mellitus, Experimental.physiopathology
Diabetic Nephropathies.physiopathology.prevention & control
Glomerular Filtration Rate.drug effects
Sodium, Dietary.pharmacology
Appears in Collections:Journal articles

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