Experimental gestational hypothyroidism evokes hypertension in adult offspring rats

Abstract

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n=13) or water-treated dams (OWTD, n=13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 ± 2.0 vs 108.8 ± 3.0 mmHg, p<0.001), SAP (157.3 ± 2.9 vs 135.7 ± 4.5mm Hg, p<0.001) and DAP (109.7 ± 1.9 vs 88.4 ± 2.6 mmHg, p<0.001) when compared to OWTD, and had lower HR (355.1 ± 8.9 vs 386.8 ± 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 ± 0.8 vs 4.0 ± 0.6 mmHg(2), p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems.

Hemodynamic properties and arterial structure in male rat offspring with fetal hypothyroidism

“…All values are means ± SEM; n = 10; repeated measure ANOVA followed by Bonferroni test was used for comparing between groups; all * p < 0.05, † p < 0.01, ‡ p < 0.001 vs. control. Contrary to the above mentioned results, Santos et al (2012) report that FH induces hypertension. Although the reason for this discrepancy is not exactly clear, explanations include difference in types of antithyroid drugs used (PTU vs. methimazole), time of drug administration during pregnancy (first day of conception until delivery vs. day 9 until delivery), and age of rats at time of BP measurement (~ 95 days vs. 60 days).…”

“…The sex-associated differences in blood pressure, observed in humans, have also been documented in animal models (Reckelhoff 2001). Finally, outcomes of impaired intrauterine growth may vary according to age of offspring ( Roland et al 2010;Karbalaei et al 2013), results that justify both ours and those of Santos et al (2012).…”

“…The fetal thyroid gland is inactive until birth (Galton et al 1999) and maternal THs are the only source of THs during fetal life (Santos et al 2012). Adverse effects of TH deficiency during fetal development have been evaluated on various systems (Chattergoon et al 2012;Karbalaei et al 2013).…”

Maternal thyroid hormones during pregnancy, childhood adiposity and cardiovascular risk factors: the Generation R Study

“…Experimental studies have shown that an adequate maternal thyroid function during gestation was necessary for the proper expression of both structural and regulatory genes in cardiomyocytes of foetal rats . Also, experimental gestational hypothyroidism in rats increased systolic and diastolic blood pressure in adult offspring . Maternal hyperthyroidism was associated with altered expression of renin‐angiotensin system components in rat pups .…”

“…Small size for gestational age children have higher risks of infant catch‐up growth and an adverse cardiovascular profile in later life . Thus far, it is not known whether first‐trimester maternal thyroid hormone levels affect childhood growth and cardiovascular development . Experimental studies have shown that an adequate maternal thyroid function during gestation was necessary for the proper expression of both structural and regulatory genes in cardiomyocytes of foetal rats .…”