Hypothyroidism and the Development of Hypertension

Low thyroid hormone (TH) in adulthood is associated with increased risk of cardiovascular disease, including risk of hypertension. The Spontaneously Hypertensive Rat (SHR), exhibits alterations in thyroid function when compared to normotensive controls. Interestingly, inhibiting thyroid gland function before 4 weeks of age prevented hypertension in the SHR, indicating that TH is involved in the etiology of SHR hypertension. However, these studies utilized tail-cuff photoplethysmography (PPG), which is known to have stress-induced artifacts, and did not compare effects in the normotensive parent strain Wistar Kyoto (WKY) rat. Therefore, it is uncertain whether TH is responsible for an elevation in baseline blood pressure or whether hypertension in the SHR is caused by abnormal TH action in the cardiovascular system. Considering this, the purpose of the present study was to investigate the effect of hypothyroidism on the SHR and its parent strain, WKY on blood pressure. To study the effect of thyroid hormone on blood pressure, we inhibited thyroid hormone production in WKY and SHR male rats with 1% KClO4 and 0.05% MMI in drinking water from 4-14 weeks-of-age. Rats were allowed to recover from treatment weeks 14-17. Blood pressure was monitored weekly by tail-cuff PPG from 4-15 weeks and by implantable remote transmitters from 11-17 weeks. Pressure natriuresis was evaluated using flame photometry. Data was consistent with previous literature that indicated hypothyroidism prevented hypertension in the SHR, but remote transmitter data indicated a comparable reduction in systolic (SAP) and mean arterial pressure (MAP) between strains. The observed difference in PPG can be explained by an exaggerated response of SAP to stress in SHRs which is normalized by hypothyroid treatment. Strain differences were observed in the effect of treatment on diastolic arterial pressure (DAP), pulse pressure (PP), heart rate, and pressure natriuresis. Endothelial dysfunction and increased arterial stiffness in the SHR provide potential explanations for differences in DAP, PP, and pressure natriuresis