Farhadi Susan A S, Dizaye Kawa F
Department of Basic Sciences/ Pharmacology Unit, College of Medicine, Hawler Medical University, Erbil, Iraq.
Int J Endocrinol. 2019 Jul 18;2019:5960563. doi: 10.1155/2019/5960563. eCollection 2019.
Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions.
Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T, and T. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates.
In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na excretion, and K excretion rates. Aliskiren was better at reducing the high blood pressure.
Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats.
甲状腺激素在包括肾脏在内的各种组织的生长和发育中起着重要作用，肾脏是肾素释放以及随后血管紧张素和醛固酮形成的主要部位。因此，甲状腺功能的任何紊乱都可能导致肾素 - 血管紧张素 - 醛固酮系统功能异常。本研究旨在探讨使用直接肾素抑制剂（阿利吉仑）和血管紧张素转换酶抑制剂（福辛普利）对甲状腺功能异常大鼠肾素 - 血管紧张素 - 醛固酮系统（RAAS）各组分的影响。
42只雄性白化大鼠分为三个亚组。第一组（6只大鼠）作为对照组。第二组（18只大鼠）作为甲状腺功能亢进组（6只大鼠为阳性对照，6只大鼠给予阿利吉仑，6只大鼠给予福辛普利）。第三组（18只大鼠）作为甲状腺功能减退组（6只大鼠为阳性对照，6只大鼠给予阿利吉仑，6只大鼠给予福辛普利）。分别通过每日口服L - 甲状腺素和丙硫氧嘧啶诱导甲状腺功能亢进和减退。在研究的第40天，处死大鼠并采集血液以测定肾素、血管紧张素I、血管紧张素II、醛固酮、促甲状腺激素、T₃和T₄。采集的血液样本还用于测定血尿素、血清肌酐、肝酶和血清电解质水平。在第1天和第40天测量血压并收集尿液。收集的尿液用于测定尿流量、钠排泄率和钾排泄率。
在甲状腺功能减退诱导的大鼠中，血清肾素水平如预期下降，而在这些甲状腺功能减退大鼠中使用阿利吉仑和福辛普利由于反馈机制使肾素水平升高。与醛固酮水平高于正常水平不同，甲状腺功能减退大鼠的血管紧张素I和II均显著低于正常水平（P <0.05）。甲状腺功能减退大鼠的血压（收缩压、舒张压和平均血压）有不显著下降。与甲状腺功能减退组相比，用阿利吉仑和福辛普利治疗这些大鼠并没有使血压降低到正常水平以下。甲状腺功能减退大鼠的血清肌酐水平也有所下降。在甲状腺功能亢进大鼠中，血清肾素、血管紧张素II和醛固酮水平升高；然而，血管紧张素I水平的升高是显著的。使用阿利吉仑和福辛普利使肾素水平无显著升高（血管紧张素I显著降低）。甲状腺功能亢进大鼠的收缩压、舒张压和平均血压显著升高。阿利吉仑和福辛普利均增加了尿流量、钠排泄率和钾排泄率。阿利吉仑在降低高血压方面效果更好。
阿利吉仑和福辛普利可降低甲状腺功能亢进大鼠的血清血管紧张素I、血管紧张素II和醛固酮水平。阻断肾素和抑制血管紧张素转换酶均导致甲状腺功能减退大鼠肾素水平反弹升高。阿利吉仑在控制甲状腺功能亢进大鼠血压方面效果更好。阿利吉仑和福辛普利可改善甲状腺功能亢进大鼠的尿流量、钠排泄率和钾排泄率。
