angiotensin-i and Hyperthyroidism

This study was conducted to evaluate the effect of eplerenone on the RAAS and kidney function in rats with thyroid hormone disorders.. This study involved 30 male Wistar albino rats, divided into three groups. The first group (N = 6) served as a control. The second group involved 12 rats with experimentally induced hypothyroidism through receiving propylthiouracil (0.05% w/v) in drinking water for one month, which was divided into two subgroups of six rats each. The first subgroup served as a positive hypothyroid control, and the second subgroup received oral daily dose of eplerenone (100 mg/kg) for 14 days. The third group included 12 rats with induced hyperthyroidism with L-thyroxin (0.0012% w/v) in drinking water, and rats in this group were also divided into two subgroups. The first subgroup served as a positive hyperthyroid control, and the second subgroup received oral eplerenone 100 mg/kg.. Eplerenone indicated a significant increase in renin and angiotensin I from 184.09 pg/ml and 178.66 pg/ml to 603.31 pg/ml and 250.88 pg/ml, respectively, meanwhile, aldosterone indicated no significant changes after inducing hypothyroidism and eplerenone administration. The induction of hyperthyroidism led to a significant increase in angiotensin I from 248.84 pg/ml to 292.22 pg/ml. Oral administration of eplerenone for 14 days caused a significant increase aldosterone from 364.23 pg/ml to 497.02 pg/ml.. Eplerenone significantly increased the serum renin and angiotensin I in hypothyroid and aldosterone and angiotensin I in hyperthyroid rats. Aldosterone in hypothyroid rats was not changed by eplerenone.

Topics: Aldosterone; Angiotensin I; Animals; Antihypertensive Agents; Eplerenone; Hyperthyroidism; Hypothyroidism; Male; Rats; Rats, Wistar; Renin; Renin-Angiotensin System

Patients with hyperthyroidism exhibit increased risk of development and progression of cardiac diseases. The activation of the renin-angiotensin system (RAS) has been indirectly implicated in these cardiac effects observed in hyperthyroidism. Angiotensin-(1-7) (Ang-(1-7)) has previously been shown to counterbalance pathological effects of angiotensin II (Ang II). The aim of the present study was to investigate the effects of elevated circulating Ang-(1-7) levels on cardiac effects promoted by hyperthyroidism in a transgenic rat (TG) model that constitutively overexpresses an Ang-(1-7)-producing fusion protein [TGR(A1-7)3292]. TG and wild-type (WT) rats received daily injections (i.p.) of triiodothyronine (T3; 7 µg/100 g of body weight (BW)) or vehicle for 14 days. In contrast with WT rats, the TG rats did not develop cardiac hypertrophy after T3 treatment. Indeed, TG rats displayed reduced systolic blood pressure (SBP) and cardiac hyperdynamic condition induced by hyperthyroidism. Moreover, increased plasma levels of Ang II observed in hyperthyroid WT rats were prevented in TG rats. TG rats were protected from glycogen synthase kinase 3β (GSK3β) inactivation and nuclear factor of activated T cells (NFAT) nuclear accumulation induced by T3.

Topics: Angiotensin I; Animals; Cardiomegaly; Cells, Cultured; Echocardiography; Glycogen Synthase Kinase 3 beta; Hyperthyroidism; Male; Myocytes, Cardiac; NFATC Transcription Factors; Peptide Fragments; Rats, Sprague-Dawley; Rats, Transgenic; Rats, Wistar; Renin-Angiotensin System; Signal Transduction; Triiodothyronine

Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin-angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1-7 (Ang 1-7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1-7, ACE2 and Mas receptor levels.. Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days.. Although plasma Ang 1-7 levels were unchanged by hyperthyroidism, cardiac Ang 1-7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1-7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1-7 levels were accompanied by increased Mas receptor protein levels.. The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH.

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Cardiomegaly; Hyperthyroidism; Male; Myocardium; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Renin-Angiotensin System

Suboptimal intrauterine conditions as changed hormone levels during critical periods of the development are considered an insult and implicate in physiological adaptations which may result in pathological outcomes in later life. This study evaluated the effect of maternal hyperthyroidism (hyper) on cardiac function in adult offspring and the possible involvement of cardiac Renin-Angiotensin System (RAS) in this process. Wistar dams received orally thyroxin (12 mg/L) from gestational day 9 (GD9) until GD18. Adult offspring at postnatal day 90 (PND90) from hyper dams presented increased SBP evaluated by plethysmography and worse recovery after ischemia-reperfusion (I/R), as evidenced by decreased LVDP, +dP/dT and -dP/dT at 25 min of reperfusion and by increased infarct size. Increased cardiac Angiotensin I/II levels and AT1R in hyper offspring were verified. Herein, we provide evidences that maternal hyperthyroidism leads to altered expression of RAS components in adult offspring, which may be correlated with worse recovery of the cardiac performance after ischemic insults and hypertension.

Topics: Angiotensin I; Angiotensin II; Animals; Animals, Newborn; Disease Models, Animal; Disease Susceptibility; Female; Hypertension; Hyperthyroidism; Male; Myocardial Reperfusion Injury; Plethysmography; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Thyroxine

Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against Ischemia/Reperfusion (I/R) injury. Type 2 Angiotensin II receptors (AT2R) are shown to be upregulated in cardiac hypertrophy observed in hyperthyroidism and this receptor has been reported to mediate cardioprotection against ischemic injury.. The aim of the present study was to evaluate the role of AT2R in the recovery of myocardium after I/R in isolated hearts from T3 treated rats. Male Wistar rats were treated with triiodothyronine (T3; 7 μg/100 g BW/day, i.p.) in the presence or not of a specific AT2R blocker (PD123,319; 10 mg/Kg) for 14 days, while normal rats served as control. After treatment, isolated hearts were perfused in Langendorff mode; after 30 min of stabilization, hearts were subjected to 20 min of zero-flow global ischemia followed by 25 min, 35 min and 45 min of reperfusion.. T3 treatment induced cardiac hypertrophy, which was not changed by PD treatment. Post-ischemic recovery of cardiac function was increased in T3-treated hearts after 35 min and 45 min of reperfusion as compared to control and the ischemic contracture was accelerated and intensified. AT2R blockade was able to return the evaluated functional parameters of cardiac performance (LVDP, +dP/dt(máx) and -dP/dt(min)) to the control condition. Furthermore, AT2R blockade prevented the increase in AMPK expression levels induced by T3, suggesting its possible involvement in this process.. AT2R plays a significant role in T3-induced cardioprotection.

Topics: AMP-Activated Protein Kinases; Angiotensin I; Angiotensin II; Angiotensin II Type 2 Receptor Blockers; Animals; Cardiomegaly; Hyperthyroidism; Imidazoles; Male; Myocardial Reperfusion Injury; Myocardium; Pyridines; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Thyroxine; Triiodothyronine; Ventricular Pressure

To produce a chronical thyrotoxicosis model in rat, and to evaluate, using spectral analysis, the involvement of the renin-angiotensin system (RAS) in short-term variability of blood pressure (BP) in experimental hyperthyroidism.. Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (T4: 0.1 mg/kg for 15 days) in Wistar rats. Control (euthyroid) rats received i.p. daily injection of the thyroxine solvent. Two series of experiments were performed in conscious and unrestrained rats. In the first series, 10 euthyroid and 14 hyperthyroid rats were surgically prepared with a femoral artery catheter to measure BP and heart rate (HR) and to collect blood samples on the last day of treatment. In the second series of experiments (n = 12 in each group), on the fifteenth day of treatment, BP and HR were recorded by telemetry in control conditions and after a specific blockade of the RAS by the angiotensin type I receptors antagonist: valsartan (10 mg/kg, i.p.). BP recordings were analysed by the Fast Fourier Transform on consecutive 204.8-s stationary periods.. The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including: tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a 3 fold-increase of plasma renin activity. Hyperthyroidism modified systolic BP (SBP) variability profiles. An amplification of low frequency (LF) oscillations (2.37 +/- 0.12 mmHg vs 1.78 +/- 0.11 mmHg, p < 0.01) was observed after T4 treatment. In hyperthyroid rats, valsartan diminished the slow fluctuations of SBP (p < 0.001) and increased the mid-frequency oscillations (2.44 +/- 0.20 mmHg vs 1.32 +/- 0.18 mmHg, p < 0.001).. The cardiovascular alterations of hyperthyroidism are reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased SBP variability in the LF range. Using the angiotensin type I receptors antagonist, valsartan, we demonstrated that the RAS impinged on the LF oscillations of the SBP in our experimental hyperthyroidism model.

Topics: Angiotensin I; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Cardiomegaly; Chronic Disease; Disease Models, Animal; Fever; Fourier Analysis; Heart Rate; Hypertension; Hyperthyroidism; Injections, Intraperitoneal; Male; Rats; Rats, Wistar; Renin; Renin-Angiotensin System; Signal Processing, Computer-Assisted; Tachycardia; Tetrazoles; Thyroid Hormones; Thyrotoxicosis; Thyroxine; Valine; Valsartan; Weight Loss

The basal levels of angiotensin I (A. I), plasma renin activity (PRA), plasma renin substrate (PRS) and plasma renin concentration (PRC) were estimated in hyperthyroid rats before and after propranolol treatment. Serum levels of triiodothyronine (T3), thyroxine (T4), angiotensin I both basal and generated by incubation of plasma samples were measured by radioimmunoassay, while, PRC and PRS were evaluated by triiodothyronine or thyroxine treatment induced a decrease in PRS and an increase in PRC whereas triiodothyronine alone produced an increase in the basal levels of angiotensin I and PRA. The propranolol in euthyroid animals not only decreased the basal levels of angiotensin I and PRA, but also prevented the PRC increase in hyperthyroid rats, while restoring at the same time the basal levels of angiotensin I and PRA.

Topics: Angiotensin I; Animals; Hyperthyroidism; Kinetics; Male; Propranolol; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System; Thyroxine; Triiodothyronine

The basal levels of angiotensin I and kinetic parameters of renin-angiotensin system were studied under control, hyper- and hypothyroidism conditions. The serum levels of triiodothyronine (T3) and thyroxine (T4) and plasma angiotensin II have been measured radioimmunoassay. Hyperthyroidism was induced by 5.5 micrograms/200 g of T3 or 100 micrograms/200 g of T4 administration for 12 days, and hypothyroidism by propylthiouracil (PTU) administration of 1 mg/200 g for 12 days. Basal levels of angiotensin I and plasma renin activity (PRA) increased after T3 injection, were not altered by T4 and decreased after PTU administration. T3 and T4 induced an increase in plasma renin concentration (PRC), while PTU induced a decrease in PRC. Plasma renin substrate (PRS) decreased in hyperthyroid rats and was unchanged by experimentally induced hypothyroidism. A good correlation between T3 serum levels and PRA was found, but there was no such correlation between T4 serum levels and PRA.

Topics: Angiotensin I; Angiotensins; Animals; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Thyroxine; Triiodothyronine