atrial-natriuretic-factor and Aortic-Diseases

To determine whether dopamine prevents deterioration of central haemodynamics and renal function in aortoiliac surgery.. Prospective, randomised and placebo-controlled.. University hospital.. Thirty patients for elective vascular surgery with implantation of an aortobifemoral or an aortobiiliac graft due to aortoiliac arteriosclerosis had infusion of dopamine 3 micrograms/kg/min or placebo during the operation and 24 h postoperatively. Thoracic epidural analgesia and general anaesthesia were used.. Central haemodynamic measurements were registered. The effective renal plasma flow (ERPF), the glomerular filtration rate (GFR), angiotensin II, aldosterone, arginine vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin and excretion of water and electrolytes were measured preoperatively, 1 h postoperatively and 24 h postoperatively.. During the operation the dopamine group had higher cardiac index and heart rate together with lower pulmonary artery wedge blood pressure. ERPF and GFR did not differ between the groups. In the dopamine group ERPF was increased in all patients at the first postoperative clearance. The fractional excretion of sodium, the per- and postoperative diuresis and AVP were increased in the dopamine group as compared to the placebo group. Postoperatively, ANP in the placebo group was raised as compared to the preoperative level.. Peroperatively, dopamine counteracted depression of left ventricular function. The increased ERPF at the first postoperative clearance in the dopamine group indicates either improved peroperative haemodynamics or a synergistic effect between dopamine and epidural sympathetic blockade. Dopamine also improved diuresis and natriuresis.

Topics: Aged; Aldosterone; Angiotensin II; Aorta, Abdominal; Aortic Diseases; Arginine Vasopressin; Arteriosclerosis; Atrial Natriuretic Factor; Blood Vessel Prosthesis; Dopamine; Endothelins; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Male; Middle Aged; Potassium; Prospective Studies; Renal Plasma Flow, Effective; Sodium

Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI.. 48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined.. Patients with a PWV above median (>7.0m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p<0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p<0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p<0.001).. Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Aortic Diseases; Atrial Natriuretic Factor; Biomarkers; Creatinine; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Pulsatile Flow; Risk Factors; Stress, Mechanical; Stroke Volume; Vascular Stiffness

C57BL/6-Kit(W-sh/W-sh) mice are generally regarded as a mast cell-deficient model, as they lack the necessary kit receptor for mast cell development. Further characterization of this strain, however, indicates that C57BL/6-Kit(W-sh/W-sh) mice also have a disruption in the Corin gene. Corin is a transmembrane serine protease critical for processing atrial natriuretic peptide (ANP) from pro-ANP through proteolytic cleavage. Pro-ANP is produced, stored and released by cardiac myocytes in response to atrial stretch and the stress generated by increased afterload such as increased ventricular pressure from aortic stenosis or myocardial infarction. ANP inhibits the effects of the renin-angiotensin system to preserve homeostasis under conditions of increased hemodynamic load, and changes in the level of its activating enzyme Corin have been observed during the progression to heart failure. Here, we investigate the effect of increased hemodynamic load on Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice. Ten-week old male mice were subjected to transverse aortic constriction for 8 weeks and were monitored for changes in cardiac structure and function by echocardiography. Hearts were collected 8 weeks after surgery for molecular and histological analyses. Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice developed rapidly progressive and substantial left ventricular dilation, hypertrophy, and markedly impaired cardiac function during the 8 weeks after surgery, compared to wildtype mice. Concomitant with this we observed increased levels of ANP transcript, but a lack of prepro-ANP or pro-ANP protein in heart tissue extracted from Corin-deficient mice. Surprisingly, fibrosis was not increased in Corin-deficient mice when compared to wildtype mice. These data indicate that Corin's involvement in ANP processing is a key element in the heart's response to increased hemodynamic load. Further, C57BL/6-Kit(W-sh/W-sh) strain is an effective model for investigating the involvement of Corin and, conversely, a less than optimal model for investigating mast cell, and immunological, functions in certain cardiovascular pathologies.

Topics: Animals; Aortic Diseases; Atrial Natriuretic Factor; Blotting, Western; Cardiomegaly; Echocardiography, Doppler; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Reverse Transcriptase Polymerase Chain Reaction; Serine Endopeptidases; Ventricular Dysfunction, Left

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular mortality and is commonly caused by hypertension. In rodents, transverse aortic constriction (TAC) is a model regularly employed in mechanistic studies of the response of the LV to pressure overload. We previously reported that inbred strains of male mice manifest different cardiac responses to TAC, with C57BL/6J (B6) developing LV dilatation and impaired contractility and 129S1/SvImJ (129) males displaying concentric LVH. In the present study, we investigated sex and parent-of-origin effects on the response to TAC by comparing cardiac function, organ weights, expression of cardiac hypertrophy markers, and histology in female B6 and female 129 mice and in F1 progeny of reciprocal crosses between B6 and 129 mice (B6129F1 and 129B6F1). Five weeks after TAC, heart weight increased to the greatest extent in 129B6F1 mice and the least extent in 129 and B6129F1 mice. Female 129B6F1 and B6 mice were relatively protected from the increase in heart weight that occurs in their male counterparts with pressure overload. The response to TAC in 129 consomic mice bearing the B6 Y chromosome resembled that of 129 rather than 129B6F1 mice, indicating that the B6 Y chromosome does not account for the differences in the reciprocal cross. Our results suggest that susceptibility to LVH is more complex than simple Mendelian inheritance and that parental origin effects strongly impact the LV response to TAC in these commonly used inbred strains.

Topics: Animals; Aortic Diseases; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Disease Models, Animal; Epigenesis, Genetic; Female; Fibrosis; Genes, Y-Linked; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; Myosin Heavy Chains; Natriuretic Peptide, Brain; Organ Size; Sex Factors; Species Specificity

Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic constriction (TAC) resulted in myocardial iNOS expression, cardiac hypertrophy, ventricular dilation and dysfunction, and fibrosis, whereas iNOS-deficient mice displayed much less hypertrophy, dilation, fibrosis, and dysfunction. Consistent with these findings, TAC resulted in marked increases of myocardial atrial natriuretic peptide 4-hydroxy-2-nonenal (a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) in wild-type mice but not in iNOS-deficient mice. In response to TAC, myocardial endothelial NO synthase and iNOS was expressed as both monomer and dimer in wild-type mice, and this was associated with increased reactive oxygen species production, suggesting that iNOS monomer was a source for the increased oxidative stress. Moreover, systolic overload-induced Akt, mammalian target of rapamycin, and ribosomal protein S6 activation was significantly attenuated in iNOS-deficient mice. Furthermore, selective iNOS inhibition with 1400W (6 mg/kg per hour) significantly attenuated TAC induced myocardial hypertrophy and pulmonary congestion. These data implicate iNOS in the maladaptative response to systolic overload and suggest that selective iNOS inhibition or attenuation of iNOS monomer content might be effective for treatment of systolic overload-induced cardiac dysfunction.

Topics: Amidines; Animals; Aortic Diseases; Atrial Natriuretic Factor; Benzylamines; Cardiomegaly; Chronic Disease; Enzyme Inhibitors; Fibrosis; Heart Failure; Hypertension; Matrix Metalloproteinase 2; Mice; Mice, Knockout; Myocardium; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Protein Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Ribosomal Protein S6; Systole; TOR Serine-Threonine Kinases; Vasoconstriction

Left ventricular hypertrophy (LVH) displays significant gender-based differences. 17beta-estradiol (E2) plays an important role in this process because it can attenuate pressure overload hypertrophy via 2 distinct estrogen receptors (ERs): ERalpha and ERbeta. However, which ER is critically involved in the modulation of LVH is poorly understood. We therefore used ERalpha-deficient (ERalpha-/-) and ERbeta-deficient (ERbeta-/-) mice to analyze the respective ER-mediated effects.. Respective ER-deficient female mice were ovariectomized and were given E2 or placebo subcutaneously using 60-day release pellets. After 2 weeks, they underwent transverse aortic constriction (TAC) or sham operation. In ERalpha-/- animals, TAC led to a significant increase in ventricular mass compared with sham operation. E2 treatment reduced TAC induced cardiac hypertrophy significantly in wild-type (WT) and ERalpha-/- mice but not in ERbeta-/- mice. Biochemical analysis showed that E2 blocked the increased phosphorylation of p38-mitogen-activated protein kinase observed in TAC-treated ERalpha-/- mice. Moreover, E2 led to an increase of ventricular atrial natriuretic factor expression in WT and ERalpha-/- mice.. These findings demonstrate that E2, through ERbeta-mediated mechanisms, protects the murine heart against LVH.

Topics: Animals; Aortic Diseases; Atrial Natriuretic Factor; Cardiotonic Agents; Constriction, Pathologic; Estradiol; Estrogen Receptor beta; Female; Heart Ventricles; Hypertrophy, Left Ventricular; Mice; Mice, Knockout; Myocardium; Ovariectomy; p38 Mitogen-Activated Protein Kinases; Phosphorylation