Converting enzyme inhibition and its withdrawal in spontaneously hypertensive rats.
When spontaneously hypertensive rats (SHR) treated at a young age with an inhibitor of angiotensin-converting enzyme (ACE) are withdrawn from treatment, their blood pressure (BP) remains below that of untreated rats. We examined the effects of ACE inhibitor treatment and its withdrawal on angiotensin-(1-7) [Ang-(1-7)], angiotensin II (Ang II) and angiotensin I (Ang I) in plasma, kidney, adrenal, heart, aorta, brown adipose tissue, lung, and brain of male SHR and normotensive Donryu rats. Rats were administered either vehicle or perindopril (3 mg/kg/day) from 6 to 10 weeks, from 6 to 20 weeks, and from 6 to 10 weeks, followed by perindopril withdrawal from 10 to 20 weeks. Angiotensin peptides and plasma levels of renin, angiotensinogen, ACE, and aldosterone were measured at 10 and 20 weeks of age. Perindopril reduced BP of both SHR and Donryu rats, although only SHR showed a reduction of BP of 19 mm Hg after perindopril withdrawal, associated with a reduction of 5% in heart weight/body weight ratio. Perindopril reduced the angiotensin II/angiotensin I ratio in all tissues by > 50%, with strain- and tissue-specific differences in the effects of perindopril on the levels of individual angiotensin peptides. None of the changes in Ang II levels persisted after perindopril withdrawal. In contrast to those of Donryu rats, plasma angiotensinogen levels of perindopril-withdrawn SHR were 14% lower than those of vehicle-treated SHR (p = 0.0356). Although the lower BP of perindopril-withdrawn SHR was not associated with an alteration in Ang II levels, the suppressed plasma angiotensinogen levels may have contributed to the lower BP of these rats. Alternatively, another action of perindopril, such as a change in cardiovascular structure, may have been responsible for the reduced BP of perindopril-withdrawn SHR.
Campbell
D J
DJ
St. Vincent's Institute of Medical Research, Fitzroy, Australia.
Duncan
A M
AM
Kladis
A
A
Harrap
S B
SB
D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D020913:Perindopril; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D010446:Peptide Fragments; D000808:Angiotensinogen; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7); D020913:Perindopril