Campbell D J, Duncan A M, Kladis A, Harrap S B
St. Vincent's Institute of Medical Research, Fitzroy, Australia.
J Cardiovasc Pharmacol. 1995 Sep;26(3):426-36. doi: 10.1097/00005344-199509000-00013.
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hypertensive rats (SHR) treated at a young age with an inhibitor of angiotensin-converting enzyme (ACE) are withdrawn from treatment, their blood pressure (BP) remains below that of untreated rats.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 In contrast to those of Donryu rats, plasma angiotensinogen levels of perindopril-withdrawn SHR were 14% lower than those of vehicle-treated SHR (p = 0.0356). Although the lower BP of perindopril-withdrawn SHR was not associated with an alteration in Ang II levels, the suppressed plasma angiotensinogen levels may have contributed to the lower BP of these rats.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perindopril, such as a change in cardiovascular structure, may have been responsible for the reduced BP of perindopril-withdrawn SHR.
幼年时用血管紧张素转换酶（ACE）抑制剂治疗的自发性高血压大鼠（SHR）停止治疗后，其血压（BP）仍低于未治疗的大鼠。我们研究了ACE抑制剂治疗及其停药对雄性SHR和正常血压的东京大鼠血浆、肾脏、肾上腺、心脏、主动脉、棕色脂肪组织、肺和脑中血管紧张素 -（1 - 7）[Ang -（1 - 7）]、血管紧张素II（Ang II）和血管紧张素I（Ang I）的影响。大鼠在6至10周、6至20周以及6至10周期间给予赋形剂或培哚普利（3 mg/kg/天），然后在10至20周期间停止给予培哚普利。在10周和20周龄时测量血管紧张素肽以及肾素、血管紧张素原、ACE和醛固酮的血浆水平。培哚普利降低了SHR和东京大鼠的血压，尽管只有SHR在停止使用培哚普利后血压降低了19 mmHg，同时心脏重量/体重比降低了5%。培哚普利使所有组织中的血管紧张素II/血管紧张素I比值降低> 50%，培哚普利对各个血管紧张素肽水平的影响存在品系和组织特异性差异。停止使用培哚普利后，Ang II水平的变化均未持续存在。与东京大鼠相比，停止使用培哚普利的SHR的血浆血管紧张素原水平比给予赋形剂的SHR低14%（p = 0.0356）。尽管停止使用培哚普利的SHR血压较低与Ang II水平的改变无关，但血浆血管紧张素原水平的抑制可能导致了这些大鼠血压较低。或者，培哚普利的另一种作用，如心血管结构的改变，可能是停止使用培哚普利的SHR血压降低的原因。
