Background-Recent reports have indicated that aldosterone is produced in extra-adrenal tissues in animals. The present study was designed to examine whether aldosterone is produced in human heart. Methods and Results-Plasma levels of aldosterone, BNP, and angiotensin-converting enzyme were measured in anterior interventricular vein (AIV), coronary sinus (CS), and aortic root (Ao), respectively, in 20 patients with left ventricular systolic dysfunction (LVSD), 25 patients with LV diastolic dysfunction (LVDD), and 23 control subjects. Aldosterone levels were significantly higher in AIV and CS than Ao in LVSD (98Ϯ10 versus 72Ϯ9 pg/mL, PϽ0.001, and 97Ϯ11 versus 72Ϯ9 pg/mL, PϽ0.001, respectively) and LVDD (87Ϯ10 versus 71Ϯ9 pg/mL, PϽ0.01, and 84Ϯ10 versus 71Ϯ9 pg/mL, PϽ0.01, respectively) groups, but no differences were observed in levels for these sites in the control group. Levels of ACE activity and BNP also were higher in AIV than Ao in both LV dysfunction groups. The difference in aldosterone levels between AIV and Ao and those in BNP and angiotensin-converting enzyme had a significant positive correlation with LVEDP and a significant negative correlation with LV ejection fraction in the LVSD group. Conclusions-Production

Aldosterone upregulates ACE mRNA expression, which is blocked by spironolactone in neonatal rat cardiocytes. Thus, spironolactone may suppress the progression of heart failure by blocking the effects of aldosterone and angiotensin II.

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The flow past a sphere moving vertically at constant speeds in a salt-stratified fluid is investigated numerically at moderate Reynolds numbers Re. Time development of the flow shows that the violation of density conservation is the key process for the generation of the buoyant jet observed in the experiments. For example, if the sphere moves downward, isopycnal surfaces are simply deformed and dragged down by the sphere while the density is conserved along the flow. (The flow pattern is inverted if the sphere moves upward. Some explanations are given in the introduction.) Then, the flow will never become steady. As density diffusion becomes effective around the sphere surface and generates a horizontal hole in the isopycnal surface, fluid with non-conserved density is detached from the isopycnal surface and moves upward to generate a buoyant jet. These processes will constitute a steady state near the sphere. With lengths scaled by the sphere diameter and velocities by the downward sphere velocity, the duration of density conservation at the rear/upper stagnation point, or the maximum distance that the isopycnal surface is dragged downward, is proportional to the Froude number Fr, and estimated well by πFr for Fr 1 and Re 200, corresponding to a constant potential energy. The radius of a jet defined by the density and velocity distributions, which would have correlations with the density and velocity boundary layers on the sphere, is estimated well by √ Fr/2ReSc and √ Fr/2Re respectively for Fr 1, where Sc is the Schmidt number. Numerical results agree well with the previous experiments, and the origin of the conspicuous bell-shaped structure observed by the shadowgraph method is identified as an internal wave.

We recently reported that oxidative stress is involved in the pathogenesis of coronary spasm. We hypothesized that oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase gene (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) might influence the pathogenesis of coronary spasm. We therefore examined the possible association between the PON1 Q192R or PAF-AH V279F polymorphisms and coronary spasm in 214 patients with coronary spasm and 212 control subjects. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. The incidence of the PON1-192R allele was significantly higher in the coronary spasm group than in the control group (65% vs 53%; P=0.0005). The PAF-AH-279F allele was not associated with coronary spasm (15% vs 16%; P=0.8781). Multiple logistic regression analysis with forward stepwise selection involving the PON1-192R allele and the environmental risk factors revealed that the most predictive independent risk factor for coronary spasm was the PON1-192R allele (significance=0.0016, OR=2.52), followed by cigarette smoking (significance=0.0007, OR=2.01). We also measured plasma levels of TBARS (thiobarbituric acidreactive substances) as a marker of oxidative stress. TBARS levels were higher in R/R types than in Q/Q types (2.115±0.086 nmol/ml [n=25] vs 1.676±0.102 nmol/ml [n=11], P<0.01). Thus, there is a significant association between the PON1-192R allele and coronary spasm; the PON1-192R allele may play an important role in the genesis of coronary spasm, probably by attenuating the suppression of oxidative stress.Paraoxonase gene Gln192Arg (Q192R) polymorphism is associated with coronary artery spasm

Background-Although previously thought to be synthesized solely in adrenal cortex, we have recently showed that aldosterone is also produced in and the expression of CYP11B2 mRNA was induced in the failing or hypertensive human ventricle. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with wide biological effects, including inhibition of renin and aldosterone production. We hypothesized that natriuretic peptides reduce the expression of CYP11B2 mRNA in the heart. Methods and Results-To test this hypothesis, we examined whether endogenous or exogenous natriuretic peptides reduce the expression of CYP11B2 mRNA using real-time reverse transcription-polymerase chain reaction. By using HS 142-1, a functional guanylyl cyclase-A type receptor antagonist, we showed that angiotensin II (AngII) pretreated with HS 142-1 increased CYP11B2 mRNA expression ( Key Words: angiotensin Ⅲ hormones Ⅲ natriuretic peptides Ⅲ polymerase chain reaction A ldosterone is a component of the renin-angiotensin-aldosterone system (RAAS), which promotes the retention of sodium and the loss of potassium, activates the sympathetic nervous system, stimulates myocardial and vascular fibrosis, and causes baroreceptor dysfunction. 1,2 Previously thought to be synthesized solely in adrenal cortex, recent animal studies have shown that aldosterone is also produced in such extraadrenal tissues as the heart and blood vessels. [3][4][5] In addition, we have recently shown that aldosterone is produced in and the mRNA expression of CYP11B2 (aldosterone synthase), the enzyme catalyzing the terminal or key step in the synthesis of aldosterone, is induced in the failing or hypertensive human ventricle. 6 -9 Recently, with the use of a cultured neonatal rat cardiocyte model, we revealed the presence of a vicious cycle, a positive feedback pathway from aldosterone to angiotensin-converting enzymes (ACEs) within the local cardiac RAAS. 10 A-type or atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP) have a wide range of potent biological effects, including vasodilating action, natriuretic action, and inhibition of the RAAS and sympathetic nervous systems. 11 Natriuretic peptides (NP) exert effects by binding to the NP-A and NP-B receptors on the cell surface that are linked to guanylyl cyclase (GC). cGMP is the main second messenger of the NP family. 12 In the recent studies, both ANP and BNP inhibited aldosterone production in cultured human and bovine adrenal cells. [13][14][15] In this study, we examined whether natriuretic peptides endogenously or exogenously suppress CYP11B2 gene expression in cultured neonatal rat cardiocytes using real-time reverse transcription-polymerase chain reaction (RT-PCR). Methods AgentsHuman angiotensin II (AngII), ANP, and BNP were purchased from Peptide Institute. HS 142-1, 16 a functional GC-A type receptor antagonist, was provided by Kyowa Hakko Kogyo Co, Ltd (Mishima, Japan). RT-PCR for CYP11B2 and GAPDH: Design of Primers and ProbesOligonucleotide prime...

In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.

The preoperative D-dimer level is an independent prognostic factor in patients with completely resected NSCLC.