oxytocin and Heart-Failure

The automatism of cardiac pacemaker cells, which is tuned, is regulated by the autonomic nervous system (ANS) and multiple endocrine and paracrine factors, including cardiovascular peptides. The cardiovascular peptides (CPs) form a group of essential paracrine factors affecting the function of the heart and vessels. They may also be produced in other organs and penetrate to the heart via systemic circulation. The present review draws attention to the role of vasopressin (AVP) and some other cardiovascular peptides (angiotensins, oxytocin, cytokines) in the regulation of the cardiovascular system in health and cardiovascular diseases, especially in post-infarct heart failure, hypertension and cerebrovascular strokes. Vasopressin is synthesized mostly by the neuroendocrine cells of the hypothalamus. There is also evidence that it may be produced in the heart and lungs. The secretion of AVP and other CPs is markedly influenced by changes in blood volume and pressure, as well as by other disturbances, frequently occurring in cardiovascular diseases (hypoxia, pain, stress, inflammation). Myocardial infarction, hypertension and cardiovascular shock are associated with an increased secretion of AVP and altered responsiveness of the cardiovascular system to its action. The majority of experimental studies show that the administration of vasopressin during ventricular fibrillation and cardiac arrest improves resuscitation, however, the clinical studies do not present consisting results. Vasopressin cooperates with the autonomic nervous system (ANS), angiotensins, oxytocin and cytokines in the regulation of the cardiovascular system and its interaction with these regulators is altered during heart failure and hypertension. It is likely that the differences in interactions of AVP with ANS and other CPs have a significant impact on the responsiveness of the cardiovascular system to vasopressin in specific cardiovascular disorders.

Topics: Angiotensins; Arginine Vasopressin; Cardiovascular Diseases; Cardiovascular System; Cytokines; Heart Failure; Humans; Hypertension; Lung; Oxytocin; Vasopressins

Pregnancy and early life create specific psychosomatic challenges for the mother and child, such as changes in hemodynamics, resetting of the water-electrolyte balance, hypoxia, pain, and stress, that all play an important role in the regulation of the release of oxytocin and vasopressin. Both of these hormones regulate the water-electrolyte balance and cardiovascular functions, maturation of the cardiovascular system, and cardiovascular responses to stress. These aspects may be of particular importance in a state of emergency, such as hypertension in the mother or severe heart failure in the child. In this review, we draw attention to a broad spectrum of actions exerted by oxytocin and vasopressin in the pregnant mother and the offspring during early life. To this end, we discuss the following topics:

Topics: Animals; Female; Heart Failure; Humans; Infant, Newborn; Oxytocin; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Vasopressins; Water-Electrolyte Balance

Neural control of the heart is regulated by sympathetic and parasympathetic divisions of the autonomic nervous system, both opposing each other to maintain cardiac homeostasis via regulating heart rate, conduction velocity, force of contraction, and coronary blood flow. Sympathetic hyperactivity and diminished parasympathetic activity are the characteristic features of many cardiovascular disease states including hypertension, myocardial ischemia, and arrhythmias that result in heart failure. Restoring parasympathetic activity to the heart has recently been identified as the promising approach to treat such conditions. However, approaches that used vagal nerve stimulation have been shown to be unsuccessful in heart failure. This review focuses on novel chemogenetic approaches used to identify the cardioprotective nature of activating neural points along the vagal pathway (both central and peripheral) while being selectively therapeutic in heart failure and obstructive sleep apnea.

Topics: Animals; Choline O-Acetyltransferase; Enzyme Activators; Heart; Heart Failure; Hemodynamics; Humans; Ligands; Muscarinic Agonists; Oxytocin; Receptors, Muscarinic; Sleep Apnea, Obstructive; Vagus Nerve

Topics: Acetylcholine; Acute Kidney Injury; Angiotensin II; Animals; Bradykinin; Diuretics; Dogs; Dopamine; Electric Stimulation; Epinephrine; Heart Failure; Hemorrhage; Humans; Hypotension; Isoproterenol; Kidney Cortex; Kidney Transplantation; Liver Cirrhosis; Norepinephrine; Oxytocin; Prostaglandins; Regional Blood Flow; Transplantation, Homologous; Ureter; Vasomotor System; Vasopressins; Vena Cava, Inferior; Water-Electrolyte Balance

Oxytocinergic actions within the hippocampal CA2 are important for neuromodulation, memory processing and social recognition. However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN-to-CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR-Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs (~15%), this expression was much more abundant in CA2 astrocytes (~40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN-to-CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, they provide the first evidence for an altered PVN-to-CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.

Topics: Animals; Astrocytes; Heart Failure; Hippocampus; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Receptors, Oxytocin

A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF.. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol.. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were significantly higher in TAC + OXT compared with TAC animals. HR sensitivity, but not contractile sensitivity, to β-adrenergic stimulation was improved in TAC + OXT hearts.

Topics: Animals; Heart; Heart Failure; Hypertrophy, Left Ventricular; Isoproterenol; Male; Myocardial Contraction; Myocardium; Neurons; Oxytocin; Rats, Sprague-Dawley

Topics: Heart Failure; Humans; Hypertrophy, Left Ventricular; Neurons; Oxytocin; Vagus Nerve Stimulation

Topics: Animals; Heart Failure; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Oxytocin; Peptide Fragments; Rats; Rats, Sprague-Dawley

Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Betamethasone; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cesarean Section, Repeat; Diabetes Mellitus, Type 1; Diastole; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypotension; Infant, Newborn; Intraoperative Complications; Norepinephrine; Oxytocin; Phenylephrine; Pre-Eclampsia; Preanesthetic Medication; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Supine Position

The hypothalamic nonapeptide vasopressin is a known player in the pathogenesis of chronic heart failure. According to the large body of clinical evidence, vasopressin has an impact on salt and water imbalance, hyponatremia, and subsequent renal insufficiency - the most common and destructive co-morbidity of patients afflicted with chronic heart failure. Despite the well-documented elevated levels of vasopressin in the blood of such patients, its expression in the magnocellular hypothalamic nuclei and transport to the posterior pituitary has not yet been investigated. In addition, the literature almost lacks the information on the contribution of another member of nonapeptide family, oxytocin, in the pathogenesis of this disease. Here we present a postmortem analysis of vasopressin and oxytocin-immunoreactive neurons and their terminals in the posterior pituitary of 8 male patients (53.8+/-9.3 years) who had died from CHF and 9 male controls (54.6+/-11.8 years). In line with previous clinical reports, our study on hypothalami of chronic heart failure patients revealed a significant increase in the relative profile density (+29%) of vasopressin-positive neurons in the hypothalamic supraoptic nucleus. Consistently we found a significant increase in the relative optic density of vasopressin-immunoreactivity in the posterior pituitary (+33%) of these patients. In contrast, the similar analysis applied for oxytocin neurons revealed no statistically significant differences to controls. In conclusion, our study provides the morphological evidence for activation of vasopressin (but not oxytocin) expression and vasopressin transport to the posterior pituitary in patients with chronic heart failure.

Topics: Cadaver; Chronic Disease; Gene Expression; Heart Failure; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Oxytocin; Vasopressins

Fatal myocardial infarction occurring in a neonate is reported. The patient presented with a clinical picture of cardiogenic shock simulating a hypoplastic left heart syndrome. Etiology of the myocardial infarction is uncertain for the coronary arteries were patent, anatomically and histologically normal, and there was no significant associated cardiac defect. The possible etiologies in relationship to myocardial infarction in the neonatal period are presented.

Topics: Acute Kidney Injury; Angiocardiography; Cardiac Catheterization; Diagnosis, Differential; Electrocardiography; Female; Heart Failure; Humans; Hypotension; Infant, Newborn; Infant, Newborn, Diseases; Myocardial Infarction; Myocardium; Oliguria; Oxytocin; Pregnancy; Shock, Cardiogenic; Wolff-Parkinson-White Syndrome