Transplantation studies of the role of the kidney in long-term blood pressure reduction following brief ACE inhibitor treatment in young spontaneously hypertensive rats.
1. Brief treatment with angiotensin-converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure associated with a relatively selective reduction in renal vascular resistance. 2. To study the possible role of the kidney in this long-term hypotensive effect, we transplanted kidneys from untreated SHR into SHR that had been treated with perindopril (3 mg/kg per day) between 6 and 10 weeks of age and also transplanted kidneys from perindopril-pretreated SHR into untreated SHR. After transplantation, the remaining native kidney was removed so that only donor kidneys remained. 3. Untreated SHR that received kidneys from perindopril-pretreated SHR showed an initial fall in blood pressure followed by a rapid increase in pressure, weight loss and early death. 4. The transplantation of kidneys from control SHR into perindopril-pretreated SHR resulted in a rise in blood pressure that obviated the long-term reduction seen normally in these animals. 5. Kidneys from perindopril-pretreated SHR may be susceptible to the high blood pressure in untreated SHR. 6. The blood pressure increase in perindopril-pretreated SHR that accompanies substitution of the native kidneys by kidneys from untreated SHR further supports the hypothesis that the kidney is responsible for the long-term pressure effects following ACE inhibition in young SHR.
Harrap
S B
SB
Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Wang
B Z
BZ
MacLellan
D G
DG
D000375:Aging / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril