Cardiac actions of thyroid hormone occur through two pathways: genomic and nongenomic. The genomic route involves the interaction of thyroxine (T3) with nuclear receptors that regulate the transcription of T3-responsive genes. In hyperthyroidism, the messenger mRNA for cardiac myocyte proteins involved in regulating intracellular [Ca++] (e.g., sarcoplasmic endoplasmic reticulum calcium-ATPase [SERCA], ryanodine channel) is increased, as are amounts of contractile proteins (e.g., myosin heavy chain, actin, troponin I). This leads to an increase in contraction and relaxation rates as ATP hydrolysis and O2 consumption increase. In the hyperthyroid state, ATP utilization is less efficient and the fractional loss of heat is greater. If left untreated, severe hyperthyroidism can result in heart failure.

Patients with inadequate thyroid function (hypothyroidism) experience depressed cardiac activity. Conversely, patients with overactive thyroid glands (hyperthyroidism) exhibit tachycardia, high cardiac output, and arrhythmias such as atrial fibrillation. In such patients, sympathetic neural activity may be increased or the sensitivity of the heart to such activity may be enhanced. Thyroid hormone has been shown to increase the density of β-adrenergic receptors in cardiac tissue. In experimental animals, the cardiovascular manifestations of hyperthyroidism can be simulated by the administration of excess thyroxine.

The body's metabolic rate is increased by thyroid hormone, resulting in arteriolar vasodilation. This causes a reduction in total peripheral resistance and an increase in cardiac output. Insulin has a positive inotropic effect on the heart, which is evident even when hypoglycemia is prevented and β-adrenergic receptors are blocked. The positive inotropic effect of insulin is potentiated by β-adrenergic receptor antagonists, and glucose transport into myocardial cells does not fully explain the enhanced contractility.

Glucagon has potent positive inotropic and chronotropic effects on the heart. While not significant in normal regulation of the cardiovascular system, glucagon has been used clinically to enhance cardiac performance. Its effects on the heart and certain metabolic effects are similar to those of catecholamines. Both glucagon and catecholamines activate adenylate cyclase to increase myocardial levels of cAMP. Glucagon activates adenylate cyclase through a different mechanism than catecholamines, but the rise in cAMP increases calcium influx through calcium channels and facilitates release and reuptake of calcium by the sarcoplasmic reticulum.

Cardiovascular abnormalities in hypopituitarism primarily relate to deficiencies in adrenocortical and thyroid function. Growth hormone, in combination with thyroxine, affects the myocardium. Growth hormone alone has little effect on the depressed heart in hypophysectomized animals, while thyroxine alone restores cardiac performance under basal conditions. However, when blood volume or peripheral resistance is increased, thyroxine alone is insufficient to restore adequate cardiac function. The combination of growth hormone and thyroxine reestablishes normal cardiac performance. In certain animal models of heart failure, administration of growth hormone alone increases cardiac output and myocardial contractility.
Thyroidhormoneexertsitscardiacactionsbytwopaths:genomicandnongenomic.Thegenomicrouteinvolvesinteractionofthyroxine(T3)withnuclearreceptorsthatregulatethetranscriptionofT3-responsivegenes.Inhyperthyroidism,messengermRNAforcardiacmyocyteproteinsinvolvedinregulatingintracellular[Ca++](e.g.,sarcoplasmicendoplasmicreticulumcalcium-ATPase[SERCA],ryanodinechannel)isincreased,asareamountsofcontractileproteins(e.g.,myosinheavychain,actin,troponinI).Consequently,theratesofcontractionandrelaxationincreaseasATPhydrolysisandO2consumptionincrease.Inthehyperthyroidstate,theuseofATPislessefficient,andthefractionallossofheatisgreater.Ifuntreated,severehyperthyroidismcanresultinheartfailure.
Cardiacactivityisdepressedinpatientswithinadequatethyroidfunction(hypothyroidism).Theconverseistrueinpatientswithoveractivethyroidglands(hyperthyroidism).Characteristically,patientswithhyperthyroidismexhibittachycardia,highcardiacoutput,andarrhythmiassuchasatrialfibrillation.Insuchpatients,sympatheticneuralactivitymaybeincreased,orthesensitivityofthehearttosuchactivitymaybeenhanced.Studieshaveshownthatthyroidhormoneincreasesthedensityofβ-adrenergicreceptorsincardiactissue(seealso ).Inexperimentalanimals,thecardiovascularmanifestationsofhyperthyroidismmaybesimulatedbytheadministrationofexcessthyroxine.
increases the body’s metabolic rate, which in turn results in arteriolar vasodilation. The consequent reduction in total peripheral resistance increases cardiac output, as explained in
Insulin has a positive inotropic effect on the heart. The effect of insulin is evident even when hypoglycemia is prevented by glucose infusions and when β-adrenergic receptors are
CHAPTER 18 Regulation of the Heart and Vasculature blocked. Indeed, the positive inotropic effect of insulin is potentiated by β-adrenergic receptor antagonists. The enhanced contractility cannot be explained satisfactorily by the concomitant augmentation of glucose transport into myocardial cells.
Glucagon has potent positive inotropic and chronotropic effects on the heart. This endogenous hormone is probably not important in normal regulation of the cardiovascular system, but it has been used clinically to enhance cardiac performance. The effects of glucagon on the heart and certain metabolic effects are similar to those of catecholamines. Both glucagon and catecholamines activate adenylate cyclase to increase myocardial levels of cAMP. The catecholamines activate adenylate cyclase by interacting with β-adrenergic receptors, but glucagon activates this enzyme by a different mechanism. Nevertheless, the rise in cAMP increases influx of Ca++ through calcium channels in the sarcolemma and facilitates release and reuptake of Ca++ by the sarcoplasmic reticulum, just as catecholamines do.
The cardiovascular derangements in hypopituitarism are related principally to the associated deficiencies in adrenocortical and thyroid function. Growth hormone affects the myocardium, at least in combination with thyroxine. In hypophysectomized animals, growth hormone alone has little effect on the depressed heart, whereas thyroxine by itself restores adequate cardiac performance under basal conditions. However, when blood volume or peripheral resistance is increased, thyroxine alone does not restore adequate cardiac function, but the combination of growth hormone and thyroxine reestablishes normal cardiac performance. In certain animal models of heart failure, administration of growth hormone alone increases cardiac output and myocardial contractility.