| ObjectiveArterial hypertension is the most common cardiovascular disease. Animal models have been used to identify the mechanisms involved in the development of hypertension. Hyperthyroidism is a pathological syndrome in which tissues are exposed to excessive amounts of circulating thyroid hormone. Thyroid hormone has many effects on the heart and vascular system, and it could cause several cadiaovascular diseases including hypertension, arrhythmia, cardiac hypertrophy, fibrosis and heart failure. This study was to designed to evaluate the changes in parameters in relation with thyroxine-induced hypertension, and also to define the changes in cardiovascular function and the mechanisms involved. The study is expected to provide a rationale for the clinical treatment of thyroxine-induced hypertension.Methods①New Zealand White rabbit were used. Rabbits were subcutaneously injected with L-thyroxine (0.5 mg/kg daily) or vehicle. Parameters including cardiac mass index, body temperature, systolic blood pressure, heart rate and the levels of plasma atrial natriuretic peptide (ANP) were observed.②Isolated perfused beating atrial model:Experiments were performed in the isolated perfused beating atria. The atria were perfused for 60 min to stabilize ANP secretion. [3H]Inulin was introduced to the pericardial fluid 20 min before the start of the sample collection. The perfusate was collected at 2-min intervals at 4℃for analyses. The control period (48 min) was followed by an infusion of acetylcholine (ACh) in order to observe the effect of ACh alone. The control period (12 min) was followed by an infusion of endothelin-1 (ET-1) for 36 min, and ET-] was followed by an infusion of ACh for 36 min. The immunoreactive ANP in perfusate and pericardium was measured by radioimmunoassay (RIA).③Hyperthyroidism was induced by administering L-thyroxine (T4,0.5 mg·kg-1,subcutaneously) daily for 16 days. Sham-treated euthyroid control rats were received only vehicle saline for 16 days. SNAP, an NO donor, was used to define the differential relaxation in the thoracic aorta from euthyroid and hyperthyroid rats. To determine the mechanisms involved changes in NO-cGMP signal pathway in the regulation of aortic relaxation from hyperthyroid rats, BAY 41-2272 (BAY) was used to activate soluble guanylate cyclase (sGC), ODQ was used to inhibit sGC, and 8-Br-cGMP was used to activate protein kinase G (PKG).Results①Thyroid hormone excess for 3 days shows characteristic changes in parameters. Cardiac mass index, body temperature, systolic blood pressure, heart rate and the levels of plasma ANP were significantly increased by 15.0%, 1.5%,33.5%,11.9%, and 37.5%, respectively, compared with the sham group. Thyroid hormone excess for 12 days shows stable phase of dynamic changes in the parameters. Cardiac mass index, body temperature, systolic blood pressure, heart rate and the levels of plasma ANP were significantly increased by 63.2%, 3.3%,58.3%,29.3%, and 365.9%, respectively, compared with the sham group. A univariate linear regression analysis showed that cardiac mass index, heart rate and the levels of plasma ANP were positively correlated with systolic blood pressure (cardiac mass index vs systolic blood pressure:r= 0.984, P<0.01; heart rate vs systolic blood pressure:r=0.989, P<0.01; the levels of plasma ANP vs systolic blood pressure:r=0.888, P< 0.01).②ACh-induced increase in atrial ANP release was attenuated in hyperthyroid hearts. The effect of ET-1 on the ACh -induced increase in atrial ANP release was attenuated in hyperthyroid hearts.③Thyroid hormone excess for 16 days showed character-istic changes in body weight,heart rate and systolic blood pressure in rats. The body weight was significantly decreased, while heart rate, pulse pressure and systolic blood pressure were increased in T4-treated rats. SNAP caused relaxation in the aorta in both euthyroid and hyperthyroid rats. However, SNAP-induced relaxation was significantly attennuated in hyperthyroid rats compared with euthyroid rats. In the presence of ODQ, SNAP-induced aortic relaxation was blocked in both euthyroid and hyperthyroid rats. BAY and 8-Br-cGMP-induced relaxation of aorta was significantly attennuated in hyperthyroid rats.ConclusionsThe effect of ET-1 accentuated the ACh -induced increase in atrial ANP release was attenuated in the pathophysiology of hyperthyroid heart. The present data also found that the attenuated effect of NO-cGMP signaling is involved in the regulation of aortic relaxation in the pathophysiology of hyperthyroidism, which may be related to the downregulation of sGC and PKG. These findings indicate that cardiac endocrine function and thoracic aortic relaxation were alterted in thyroxine-induced hypertensive experimental models.
|
PDF Full Text Request