ISSN:
1432-1912
Keywords:
Key words Calcium handling
;
α1-adrenoceptors
;
Hyperthyroidism
;
Hypothyroidism
;
Tissue
;
catecholamines
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract We investigated the influence of hyper- and hypothyroidism on basal parameters of isolated perfused hearts of rats. In addition the effects of different extracellular calcium concentrations ([Ca2+]o), the calcium entry promoter Bay K8644 and the α1-adrenoceptor agonist methoxamine were investigated. Since alterations in α-adrenoceptor density could explain the increased sensitivity to methoxamine in hearts from hypothyroid rats, α1-adrenoceptor density in the left ventricle was also established. Different time-schedules of exposure to hyper- and hypothyroidism were used to investigate whether the influence of chronic dysthyroid states on α1-adrenoceptor density is transient and time-dependent. Simultaneously myocardial noradrenaline and adrenaline tissue concentrations were determined, since they might correlate with the observed changes. Hyperthyroidism was induced by feeding rats for 1, 4 and 8 weeks with 5 mg/kg L-thyroxine (T4)- containing rat chow. Hypothyroid rats were obtained by adding 0.05% propylthiouracil (PTU) to the drinking water during 1, 4 and 8 weeks. For the functional experiments animals were treated during 4 weeks, to mimic the clinical situation of a chronic endocrine disease. Langendorff hearts from hyperthyroid hearts showed an increased maximally developed relaxation velocity, whereas Langendorff hearts from hypothyroid rats showed an increased left ventricular pressure (LVP). We observed an increased maximal inotropic response to [Ca2+]o in hearts from both hyperthyroid and hypothyroid rats, indicating that both dysthyroid states interfere with the handling of calcium ions by the contractile apparatus. Unchanged responses to Bay K8644 in hearts from hyperthyroid and depressed responses in hearts from hypothyroid rats suggest that the involvement of L-type calcium channels is rather unlikely. Furthermore, the reflex increase in coronary flow in response to enhanced contractile force appeared to fail in hearts from hypothyroid rats. Sensitivity of the response to methoxamine was increased in hearts from hypothyroid rats, which was accompanied by a decrease in the number of myocardial α1-adrenoceptors. Both T4 and PTU treatment resulted in a non-transient decrease of α1-adrenoceptor density in left ventricular tissue. Furthermore, hypothyroidism increased the percentage of α1A-binding sites, whereas in hyperthyroidism the distribution of the α1-adrenoceptor subtypes was not affected. Myocardial tissue concencentrations of noradrenaline and adrenaline were unchanged in hyperthyroid rats and decreased in hypothyroid rats. The present study indicates that thyroid hormones have a direct rather than a sympathetically mediated effect on α1-adrenoceptor mediated myocardial functions.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00166902
