Adrenergic receptors and cardiovascular effects of catecholamines.

Activation of the sympathetic nervous system is responsible for the body's "fight or flight" reaction. The physiological responses to the activation of the sympathetic nervous system and adrenal medulla are mediated through the action of the endogenous catecholamines norepinephrine (or noradrenaline) and epinephrine (or adrenaline) on adrenergic receptors. Adrenergic receptors belong to the superfamily of G protein-coupled receptors (GPCR). Adrenoceptors are divided into alpha1, alpha2, beta1, beta2 and beta3 receptors. Norepinephrine stimulates both subtypes of α receptors and ß1 receptors. Epinephrine stimulates all subtypes ofα and ß adrenoreceptors. α1 adrenergic receptors, coupled to stimulatory Gq proteins, activate the enzyme phospholipase C and are mainly found in the smooth muscle cells of blood vessels and urinary tract, where they induce constriction. α2 receptors are coupled to inhibitory Gi proteins, that inactivate adenylyl cyclase, decreasing cyclic adenosine monophosphate (AMP) production. They are mainly found in the central nervous system, where their activation results in a decreased arterial blood pressure. ß1 adrenoreceptors predominate in the heart, activate the Gs-adenylyl cyclase -cAMP-protein kinase A signaling cascade, and induce positive inotropic and chronotropic effects. ß2 adrenoreceptors are distributed extensively throughout the body, but are expressed predominantly in bronchial smooth muscle cells. ß2 adrenergic receptors activate adenylyl cyclase, dilate blood vessels and bronchioles, relax the muscles of the uterus, bladder and gastrointestinal duct, and also decrease platelet aggregation and glycogenolysis. ß3 receptors can couple interchangeably to both stimulating and inhibiting G proteins. They are abundantly expressed in white and brown adipose tissue, and increase fat oxidation, energy expenditure and insulin-mediated glucose uptake. This review details the regulation of cardiac and vascular function by adrenergic receptors.

Acute Stress Cardiomyopathy: Heart of pheochromocytoma.

Stress cardiomyopathy (SCM) is a syndrome characterized by transient regional systolic dysfunction of the left ventricle in the absence of angiographic evidence of coronaropathy. This abnormality is associated with high levels of catecholamines. Stress cardiomyopathy is also called Takotsubo (TS) cardiomyopathy. Pheochromocytoma crisis can occur spontaneously or can be precipitated by manipulation of the tumor, trauma, certain medications or stress for example during non-adrenal surgery. The main drugs leading to pheochromocytoma crisis include D2 dopamine receptor antagonists, noncardioselective ß-adrenergic receptor blockers, tricyclic antidepressants and related neurotransmitter uptake blockers, sympathomimetics, certain peptide and steroid hormones and several agents used during induction of anesthesia. Patients can develop symptoms of heart failure associated with tachyarrhythmia, cardiogenic shock with hypotension and collapse, or apparent acute coronary syndromes. This review describes pathophysiology, epidemiology, diagnosis criteria and management of SCM.

Imbalanced Angiogenesis in Peripartum Cardiomyopathy　- Diagnostic Value of Placenta Growth Factor.

BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001). CONCLUSIONS: Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.

Associations between risk factors in childhood (12-13 years) and adulthood (48-49 years) and subclinical atherosclerosis: the Kaunas Cardiovascular Risk Cohort Study.

BACKGROUND: The data on the childhood determinants of adult cardiovascular disease (CVD) are lacking in populations of Eastern Europe that are characterised by substantially high CVD mortality. From a public health perspective, it is important to identify high-risk individuals as early as possible in order to have the greatest benefit of preventive interventions. The aim of this study was to evaluate the associations of childhood and adulthood traditional risk factors with subclinical atherosclerosis and arterial stiffness in a Lithuanian cohort followed up for 35 years. METHODS: The study cohort consisted of 380 adults aged 48-49 from Kaunas Cardiovascular Risk Cohort study, who were followed up since childhood (12-13 years). The baseline survey (1977) included blood pressure (BP) and anthropometric measurements and sexual maturity scale. In the follow-up survey (2012), BP, anthropometric and lipids measurements, interview about smoking, measurement of carotid intima-media thickness (IMT) and determination of pulse wave velocity (PWV) were performed. Two types of general linear models were applied to test the associations of childhood and adulthood risk factors with IMT and PWV. Model 1 included only childhood variables. In model 2, adulthood variables were added to childhood variables. RESULTS: In linear regression model with childhood variables childhood systolic BP (ß = 0.014; p = 0.016) and BMI (ß = 0.006; p = 0.003) were directly associated with IMT only in women. When adulthood variables were included into regression model, the association between childhood systolic BP and IMT remained significant (ß = 0.013; p = 0.021), while childhood BMI was not associated with IMT (ß = 0.003; p = 0.143). Additionally, association of adult smoking and IMT was found in women (ß = 0.033; p = 0.018). IMT of men was directly related to adult systolic BP (ß = 0.022; p = 0.018) and inversely to HDL cholesterol level (ß = -0.044; p = 0.021). PWV was directly associated only with adult systolic BP in both genders (ß = 0.729 for men and ß = 0.476 for women; p = 0.001). CONCLUSIONS: Sex differences in the associations between childhood and adulthood risk factors and subclinical atherosclerosis were found. The results of the study support efforts to reduce conventional risk factors both in childhood and adulthood for the primary prevention of atherosclerosis.

Incidentally diagnosed malignant coronary artery anomaly: a clinical case.

The incidence of congenital coronary artery anomalies is estimated to range between 1% and 2% in the general population. The separate types of coronary artery anomalies are even rarer - the left main coronary artery arising from the right coronary sinus and passing between the thoracic aorta and the pulmonary artery is one of them. In this case, the segment of the artery that courses between the aorta and the pulmonary artery is prone to compression, especially during heavy exercise. Outcomes may be fatal due to myocardial hypoperfusion, which is associated with sudden cardiac death especially among children, young adults, and athletes. Nowadays, innate coronary artery anomalies may be incidentally diagnosed in older age using new investigation methods such as computed tomography angiography.