The Endocrine Heart

	Antonio J. Pasca. *
Sanatorio Hurlingham, Buenos Aires, Argentina

The decrease of physical activity, the increment of population age, the increase of Diabetes mellitus (DBT) incidence and fundamentally, the high rates of Obesity (O), are the basic causes which allow the peak and perpetration of cardiovascular diseases.

Overweight (S) is associated with a higher morbid mortality, especially the cardiovascular one [1-4], due to its connection with diverse pathologies. Probably, the S and the O could represent the lack of adaptation among the ancestral metabolism, designed with a maximum efficiency for saving energy and storage of fatty reserves, and the present toxic environment. (Figure 1).

The deleterious actions of O on the myocardium and its functionality are expressed in a direct and indirect way (Figure 2).

Indirect Way: The adipose tissue has an important immunity and endocrine role [5]. In the O there is more production of toxic substances in the cardiovascular apparatus, such as resistin, TNF-α, leptin, PAI 1, interleukin-6, angiotensinogen, among others, and less secretion of cardiovascular protection substances, especially represented by the adiponectin [6].

The visceral adipose tissue excess stimulates the lipolytic action, increasing the atherogenic risk, which can conclude in diverse clinical manifestations of coronary heart disease.

In this metabolic misbalance, the hyperinsulinemia reduces the endothelial vascular constriction, action which is exacerbated by the neuropeptide Y. The Insulin, in this fisiopatologic disorder state, stimulates the sympathetic nervous system (powering the exchange Na⁺/H⁺), increases the renal reabsortion of the chloride of sodium, modifies the ionic transport of the cellular membrane (stimulation of the bomb Na⁺/K⁺, accumulation of Ca⁺⁺ intracellular, etc.), facilitates the answer outlying vascular constrictor of the agonists of angiotensin II and noradrenalin, and engenders for its mitogenic action the hypertrophy of the vascular cells, creating the favourable means for the appearance and development of the Arterial Hypertension (HTA). Meanwhile, permanent sympathetic stimulation, as a TSUNAMI derived endocrinologic of the hypersecretion of the cell, added to other multiple substances, combined with the multiple genetic alterations in the obese organism, generates more INSULIN RESISTANCE, which constitutes the substrate princess for the development of the DBT type II. Therefore, we will have O, dyslipidemia, hyperinsulinemia, Insulin resistance, HTA and DBT type II in addition to the chronic inflammatory state and associate protombotic. These are constitutive elements for the Metabolic Syndrome [7 -10].

In the S y O, the leptin (hyperleptinemia – leptin resistance) where loses the primary function of protecting the organism against faulty nutritional states and preserves the stimulate action of the sympathetic activity, principally in specific hypotalamics areas linked with the cardiovascular regulation, having preferably renal consequences that bears to the rise of the values tenses. Also, significant leptin concentrations are fundamentally associated with the damage of arterial distensibility in obese teenagers.

Various studies have pointed out that the excess of weight is related with a bigger risk of type DBT II, and the harmful known consequences on the cardiac cells. The cardiomyopathy metabolic diabetic is real and involves a great number of patients, many of who will develop a dilated cardiomyopathy that lead to the heart flaw.

Direct way: The O would act noxiously by itself in a direct way on the cardiac cells, because trying to satisfy the metabolic necessities of an obese organism, the heart should appeal to an increase of the volume minute, which depends on the systolic volume, allowing the development of a hypertrophy ventricular left and a state of diastólic dysfunction. But, in occasions, it also takes place a systolic dysfunction as a result of the dilation of the left cavities leading to an extensive cardiomyopathy [11- 12].

The O and the Metabolic Syndrome share the state of Insulin – Leptin resistance [13], depending, among other things, on the increment of endocrinologics substances secreted by the ectopic adyipocite, being the myocardium an elector of this endocrine metabolic disorder - that turns it into his own traditional victim, affecting its metabolism and function, giving origin to: ventricular hypertrophy, interstitial fibrosis, microvasculars and subcells transformations (Figure 3).

Hypertrophy ventricular main determinants are the hemodynamic load (volume - pressure), genetic and environmental factors (age, generate, race, etc.) and the factors trofics (angiotensin II, catecolaminas, insulin, endotelin, etc). Somehow, the S and the O impact in all them.

The hypertrophy ventricular left is the fisiopatologic substrate of the myocardial ischemic, the alteration of the contractility and the one filled ventricular left and the ventricular arrhythmia can respectively open the way to the coronary, heart inadequacy and sudden death.

The system renin - angiotensin is equally highly stimulated in the O; the angiotensin II abundance causes, on one hand, an increment of tense them as a result of an enlarged VI post-load (outlying vasoconstrition), and on the other hand, a hypertrophy of the cardiac cell and an aldosteron liberation increase. These last two constituents propietate the myocardial interticial fibrosis. The left ventricular hypertrophy derives in the diastolic dysfunction which is accompanied by the increase of the myocardic angiontensin II receivers, estimulating inflammatory citoquins, the reduction of the density of the capillary ones with concomitant mitochondrials alterations. They accelerate the myocardic cell apoptosis and the installation of the cardiomyopathy caused by O [11].
 
In cases of O, the endothelial function is altered with a abnormal endothelial reactivity, given to a reduction in the liberation and action of the nitric oxide that reduces the effects on the cardiac and vascular function. That is to say, an interference exists mainly in the modulation of the inotropic and cronotropic myocardium, the cycle of the Ca⁺⁺, the autonomous transmission, the breathing mitochondrial, the consumption of myocardic oxygen, the stimulation of the vagal tone, the anti-trombotic and anti-inflammatory activity.

Diverse rehearsals affirm the microalbuminuria (accting as an important sign of endothelial renal damage). It has been related to central adiposity and the insulin resistance states.
Results logical to suppose the most influential endocrine gland dysfunction in the organism lies on the vascular endothelia severely committed in the O.

Some cardiac cells in the auricles (in smaller grade in the ventricles) have a dual nature: secretor – contractile. They are the denominated cardiac endocrine cells where the natriuretic peptide is elaborated who has a supreme relevance in the control of the cardiovascular apparatus [14-19]. The Atrial Natriuretic Factor is mainly stored in the right auricle and it is liberated as a consequence of the distension of the same one, taking fundamental place in: renal vascular constriction, natriuresis, decrease of cellular proliferation, etc. It neutralizes the effects of the adrenergic system, renin-angiotensin-aldosteron and the arginin vasopresin. Has lipolitic actions, modulates digestive secretions and it is an excellent biochemical precocious marker related to the development, progression and prediction of several cardiopathies.

The natriuretic peptide produced in the brain is essentially accumulated in the miocardyum of the ventricles. Although it can operate on the filled of both ventricles, it does less than the natriuretic auricle peptide. Steel generating natriuresis and vascular constriction and it interferes in the regulation of the process of ventricular hypertrophy.

The natriuretic peptide type C, is primarily located in blood and the SNC. It would possibly act jointly with the renin - angiotensin system on the regulation of the vascular tone.

The adiponectin is a substance exclusively generated by the fatty fabric with clear protective effects against the atheroesclerosis and the diabetes. Causing basically the stimulation of nitric oxidize and the increase of the insulin sensitivity, the suppression of the molecular adhesion in the endothelial cells induced by the expression of the alpha factor of necrosis tubular, the inhibition of growth factors that induce to the proliferation of the cells of the flat muscle, the detention of the transformation of the macrophages in foamy cells, hinders the expression of the glucogenetic enzymes and it reduces the production of endogenous glucose.

Some rehearsals would indicate that the grelin, a hormone made essentially in the gastric mucous, who powers appetite, would reduce the cardiovascular risk in the obese ones, due to its down regulation on the renal nice activity and decrease of the blood pressure. Additionally, it modifies the function of the myocardium, improving the conduction, the contractility especially in the insufficient heart.

In general, the O is considered a severe pathological state, especially for the cardiac cell It propitiates the unfolding of multiple types of fisiopathologic answers, mainly endocrinologic ones which should be kept in mind in the evaluation and treatment of the obese patients (Figure 4).

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CV of the author

- Médico Cardiólogo Universitario. Universidad del Salvador. Argentina
- Editor Asociado de la Revista de la Federación Argentina de Cardiología.
- Jefe de Cardiología Especialidades Médicas Villa Bosch, Buenos Aires, Argentina.
- Jefe de Cardiología Nuevo Sanatorio Hurlingham, Buenos Aires, Argentina.

Publication: November 2007

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