Brief treatment of SHR with an ace inhibitor fails to cause long-term normotension but markedly increases mortality.
1. We examined the effect of three doses (0.03, 0.3 and 3 mg/kg per day) of the angiotensin converting enzyme (ACE) inhibitor, perindopril, on the long-term blood pressure of spontaneously hypertensive rats (SHR) of the Okamoto strain after treatment during the developmental stage of hypertension development. 2. While the 0.03 mg/kg per day dose, given between the ages of 4-10 weeks of age, failed to lower blood pressure, the two higher doses resulted in normotension over this treatment period as did the highest dose given between the ages of 4-20 weeks of age. 3. Only the 0.3 mg/kg per day dose resulted in a moderate (17%) long-term fall in blood pressure upon cessation of treatment when compared to untreated SHR controls. The highest dose, given over the 4-20 week period resulted in a significant rebound hypertension above the blood pressure level of untreated, control SHR. 4. The 3 mg/kg per day dose, whether given over the 4-10 or 4-20 week treatment period, resulted in 100% mortality in these groups by 52 weeks of age. There were no deaths in the groups receiving the two lower doses. 5. We conclude that treatment of SHR with perindopril during the developmental phase of hypertension development results in only a modest fall in long-term blood pressure upon cessation of treatment and that the relationship between the dose of this ACE inhibitor and long-term blood pressure is not linear. The 100% mortality in the two groups receiving the highest dose of perindopril may be due to either a toxic action of this drug or vascular rupture due to insufficient hypertrophy for the rapid rise in blood pressure upon cessation of treatment.
Lan
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Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Di Nicolantonio
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Bramich
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Morgan
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D000375:Aging / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008136:Longevity; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril