Humans ; Hypertension ; Sympathetic Nervous System ; metabolism ; pathology

Humans ; Hypertension ; metabolism ; pathology ; Transient Receptor Potential Channels ; metabolism ; physiology

Humans ; Hypertension, Pulmonary ; metabolism ; Iron ; metabolism ; Metabolic Diseases

OBJECTIVETo explore potential divergent glycolytic metabolism gene changes between left and right ventricle in the monocmtaline (MCT) induced pulmonary arterial hypertension (PAH) rat model.

METHODSPAH was induced by a single subcutaneous injection of MCT (50 mg/kg) in rats. Control rats were injected with normal saline. MCT-PAH rats were randomly divided into MCT-2week, MCT-3week and MCT-4week groups (MCT-2w, 3w, 4w). At the end of study, the hemodynamics and right ventricular hypertrophy were compared among groups. The expression levels of proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP nick end labeling (TUNEL) in left and right ventricular cells were compared. The glycolytic key candidate genes expression was screened between two ventricles.

RESULTSAfter three to four weeks MCT injection, mean pulmonary arterial pressure, right ventricular systolic pressure and right ventricular hypertrophy index were all significantly increased compared to control group (all P < 0.05). Both left and right ventricular morphology and structure changes were observed in all PAH rats and were similar between left and right ventricular cells. Left and right ventricular cells increased while apoptotic cells decreased in proportion to the duration post MCT injection and the PCNA positive cells in the right ventricle were higher than in the left ventricle in rats post 3 and 4 weeks MCT injection (P < 0.05). The HK1, HK2, PDHα1 and LDHA mRNA expression in the left ventricle and LDHA mRNA expression were significantly upregulated after 4 weeks MCT injection compared to control rats (all P < 0.05). Moreover, HK1 mRNA expression in the left ventricle was significantly higher in the MCT-PAH-4w group than in MCT-PAH-3w group (P < 0.05). Immunohistochemistry analysis evidenced increasing HK1 positive cells in both left and right ventricle in proportion to MCT injection time and positive HK1 cells were significantly higher in the right ventricle than in left ventricle of MCT-PAH-3w and MCT-PAH-4w rats. Furthermore, the HK1 protein expression in left ventricular tissue form MCT-PAH-4w group and in right ventricular tissue from MCT-PAH-3w and MCT-PAH-4w groups were also significantly upregulated compared to control group (P < 0.05).

CONCLUSIONSEnergy metabolic shift occurs both in the left and right ventricles in this PAH model. Upregulated HK1 expression appeares earlier in right ventricle compared to left ventricle. Interference on right ventricular glycolysis may be a potential novel therapy target of PAH.

Animals ; Gene Expression ; Heart Ventricles ; metabolism ; Hemodynamics ; Hypertension ; Hypertension, Pulmonary ; metabolism ; Hypertrophy, Right Ventricular ; metabolism ; Lung ; Monocrotaline ; Rats

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.
Acute Coronary Syndrome/metabolism ; Arrhythmias, Cardiac/metabolism ; Heart Failure/*metabolism ; Humans ; Hypertension, Pulmonary/metabolism ; Natriuretic Peptides/*metabolism ; Sepsis/metabolism

Adrenomedullin ; metabolism ; Child ; Endothelin-1 ; metabolism ; Female ; Heart Defects, Congenital ; complications ; Humans ; Hypertension ; metabolism ; Hypertension, Pulmonary ; metabolism ; Male ; Nitric Oxide ; metabolism

Sustained activation of sympathetic nervous system in response to stimulation of a wide variety of stress factors is an independent risk factor for the development of essential hypertension. Adrenal hormone biosynthesis pathway as an important part of the sympathetic nervous system consists of hormones, neurotransmitters, receptors, and a variety of synthases and invertases. In this article, we have systematically reviewed research progresses made in elucidating the interactions between genes of the adrenal hormone biosynthesis pathway and stress factors in the pathogenesis of essential hypertension.
Animals ; Hormones ; metabolism ; Humans ; Hypertension ; genetics ; metabolism ; pathology ; Sympathetic Nervous System ; metabolism ; pathology

MicroRNA(miRNA) is involved in virtually all biologic processes, including cellular proliferation, apoptosis, and differentiation. Thus, miRNA deregulation often results in impaired cellular function and disease development, so miRNAs have potential therapeutic relevance. The elucidation of these processes regulated by miRNAs and the identification of novel miRNA targets in the pathogenesis of hypertension is a highly valuable and exciting strategy that may eventually led to the development of novel treatment approaches for hypertension. Several mechanisms have been implicated in the pathogenesis of hypertension: overactivation of therenin-angiotensin-aldosterone system (RAAS), dysfunction of the vascular endothelium, damnification of vascular smooth muscle. To maintain and restore target organ expression of miRNA stable may be a new strategy for treatment of hypertension. The article reviews pathogenesis of miRNA and hypertension, researches of miRNAs as biomarker and therapeutic target, discusses advances in miRNA-based approaches that may be important in treating hypertension.
Animals ; Biomarkers ; metabolism ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Molecular Targeted Therapy

Animals ; Cardiovascular Diseases ; metabolism ; Humans ; Hydrogen Sulfide ; metabolism ; Hypertension ; metabolism ; Signal Transduction ; physiology

BACKGROUNDHypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H(2)S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension.

METHODSTwenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H(2)S level was detected by a modified method with a sulfide electrode. Data were presented as mean +/- standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H(2)S as well as to the systolic pressure against the plasma H(2)S/Hcy ratio.

RESULTSPlasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H(2)S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68 +/- 9.69) micromol/L vs (6.62 +/- 4.79) micromol/L (t = 2.996, P < 0.01); H(2)S: (51.93 +/- 6.01) micromol/L vs (65.70 +/- 5.50) micromol/L) (t = -8.670, P < 0.01)). The ratio of plasma H(2)S/Hcy in children with hypertension was 5.83 +/- 2.91, while that of the control group was 11.60 +/- 3.30, and the difference is significant with a t = -6.610 and P < 0.01. A negative correlation existed between plasma Hcy and H(2)S concentrations, r = -0.379, P < 0.05. And a negative correlation was found between systolic blood pressure and the plasma H(2)S/Hcy ratio, r = -0.687, P < 0.05.

CONCLUSIONThere was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.

Adolescent ; Child ; Female ; Homocysteine ; metabolism ; Humans ; Hydrogen Sulfide ; metabolism ; Hypertension ; etiology ; metabolism ; physiopathology ; Male ; Systole