The blood pressure reduction produced by an early ACE inhibition in LH rats persists long after treatment withdrawal and is associated with an improvement in renal function. The combination of low doses of perindopril and losartan reveals a long-term effect similar to that of a monotherapy with a higher dose of perindopril.
The aims of the present work were to determine whether a brief renin-angiotensin system blockade with AT1 receptor antagonist or angiotensin-converting enzyme inhibitor may provide long-lasting protection against hypertension and proteinuria in both young and adult Lyon hypertensive (LH) rats. Young pre-hypertensive Lyon hypertensive rats were orally treated with 5, 10, or 20 mg/kg/d of losartan, or with 0.4 mg/kg/d of perindopril from 3 to 12 weeks of age. Adult Lyon hypertensive rats were treated with 10 mg/kg/d of losartan, 0.4 mg/kg/d of perindopril, or a combination of both from 12 to 20 weeks of age. Telemetric blood pressure (BP) and urinary protein excretion were evaluated during and after treatment cessation. In young prehypertensive Lyon hypertensive rats, losartan fully prevented the hypertension and proteinuria; these effects were dose dependent and persisted long after treatment withdrawal. When renin-angiotensin system blockade was initiated in adult Lyon hypertensive rats with established hypertension, 10 mg/kg/d of losartan or 0.4 mg/kg/d of perindopril induced a significant regression in both blood pressure (15%-20%) and proteinuria (40%-50%) as did in young Lyon hypertensive rats; the combination treatment produced an additional effect only on blood pressure. After treatment cessation, a reduction in blood pressure persisted in all the pretreated adult Lyon hypertensive rats whereas the effect on proteinuria was less marked. In conclusion, whatever the blocker used, an early renin-angiotensin system blockade in prehypertensive Lyon hypertensive rats induces a durable prevention of hypertension and associated renal alterations. The similar renin-angiotensin system blockade in adult Lyon hypertensive rats provides a regression of hypertension and proteinuria, but the persistence of these beneficial effects is less pronounced than in young Lyon hypertensive rats, thus suggesting that the treatment with renin-angiotensin system blockers should be initiated as early as possible before the full expression of hypertension, to achieve the maximal long-lasting effects in mature stage.
To determine whether the persistent antihypertensive effect observed after withdrawal of angiotensin-converting enzyme inhibition was specific and whether it was associated with durable improvement of renal function. Lyon hypertensive (LH) rats were treated from 3 and 12 weeks of age with perindopril at the dose of 0.4 (P0.4) or 1.5 (P1.5) mg·kg(-1)·d(-1), with double (hydralazine 75 mg·kg(-1)·d(-1) and hydrochlorothiazide 15 mg·kg(-1)·d(-1)), or triple antihypertensive therapy (reserpine 0.75 mg·kg(-1)·d(-1) was added). Blood pressure (BP) was recorded by telemetry, and renal functions were evaluated in freely moving rats. Despite similar BP reduction after perindopril withdrawal in P0.4 and P1.5 groups, greater decrease in proteinuria was observed in P1.5 group. Double or triple therapy prevented the hypertension of LH rats, but without any persistent antihypertensive or antiproteinuric effect after its withdrawal. Salt load elicited an increase in BP that was similar in untreated LH and both perindopril-pretreated groups (+30 mm Hg), but more pronounced in double therapy–pretreated or triple therapy–pretreated groups (+50 mm Hg). The pressure–natriuresis curve shifted to lower BP levels in P0.4 and P1.5 groups, whereas it was blunted in double and triple therapy groups. Angiotensin-converting enzyme inhibition has a durable renoprotection after treatment withdrawal that is independent of BP lowing.
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