Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS)‎ in Rats with Thyroid Dysfunction

Abstract EN

Background and Objectives.

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.

Method.

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, T3, and T4.

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.

Results.

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.

Conclusion.

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.