HYPERLIPIDEMIA IS SECONDARY TO PROTEINURIA AND IS COMPLETELY NORMALIZED BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN HYPERTENSIVE FAWN-HOODED RATS

Two substrains of the fawn-hooded (FH) rat have been developed, one of which develops progressive hypertension and proteinuria, the FHH, and one which shows little increase in blood pressure and no renal damage , the FHL. Other hypertensive rodent models show primary metabolic dis turbances before the development of renal damage, notably hypertriglyc eridemia, which may also contribute to progression of renal disease. I n this study we evaluated whether hyperlipidemia is a primary disturba nce in FHH, or only occurs secondary to proteinuria. Lipid levels were determined before and after development of proteinuria, and compared to those found in age-matched FHL. We also determined whether reducing proteinuria with lisinopril would normalize lipid levels in aging FHH . At 4 weeks of age, proteinuria was very low (2-3 mg/day) in both FHH and FHL. While proteinuria increased steadily in aging FHH, reaching 350 +/- 62 mg/day at 40 weeks, much less increase was observed in FHL over the same period (32 +/- 5 mg/day at 40 weeks). Blood pressure was markedly higher in adult FHH than in FHL (158 +/- 2 vs. 129 +/- 2 mm Hg, p < 0.01). In 4-week-old FHL and FHH, plasma cholesterol levels we re similar. Subsequently, cholesterol increased in FHH, reaching 3.4 /- 0.9 mmol/l at 40 weeks, whereas cholesterol was barely affected by aging in FHL (2.1 +/- 0.2 mmol/l at 40 weeks). At 4 weeks, triglycerid e levels were lowest in FHH. Subsequently, triglycerides increased in FHH, reaching 3.5 +/- 1.5 mmol/l at 40 weeks, as compared to 1.3 +/- 0 .2 mmol/l in FHL. Besides a transient increase in triglyerides in lisi nopril-treated FHH at 11 weeks, increments in blood pressure, proteinu ria, cholesterol, triglyocerides and apolipoproteins A-I, B and E agin g FHH were effectively prevented by lisinopril. These data strongly su ggest that there is no primary difference in lipid metabolism between FHH and FHL and that changes in plasma lipids in FHH as compared to FH L are all secondary to proteinuria.