Durable improvement of renal function after perindopril withdrawal in Lyon hypertensive rats.
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.
Faculté de Pharmacie, Centre National de la Recherche Scientifique FRE 3075, Université de Lyon 1, Lyon, France.
Gaëlle
G
Naelten
Kiao-Ling
KL
Liu
Ming
M
Lo
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D020913:Perindopril / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats
D020913:Perindopril