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Ventricular myocytes are known to show increased expression of the cardiac hormones atrial and brain natriuretic peptide (ANP and BNP, respectively) in response to pathological stress on the heart, but their function during the progression of nonischemic dilated cardiomyopathy remains unclear. In this study, we crossed a mouse model of dilated cardiomyopathy and sudden death, which we generated by cardioselectively overexpressing a dominant-negative form of the transcriptional repressor neuron-restrictive silencer factor (dnNRSF Tg mice), with mice lacking guanylyl cyclase-A (GC-A), a common receptor for ANP and BNP, to assess the effects of endogenously expressed natriuretic peptides during progression of the cardiomyopathy seen in dnNRSF Tg mice. We found that dnNRSF Tg;[GC-A.sup.-/-] mice were born normally, but then most died within 4 wk. The survival rates among dnNRSF Tg;[GC-A.sup.+/-] and dnNRSF Tg mice were comparable, but dnNRSF Tg;[GC-A.sup.+/-] mice showed greater systolic dysfunction and a more severe cardiomyopathic phenotype than dnNRSF Tg mice. Collectively, our findings suggest that endogenous ANP/BNP protects the heart against the death and progression of pathological remodeling in a mouse model of dilated cardiomyopathy and sudden death. neuron-restrictive silencer factor; guanylyl cyclase-A; cardiomyopathy; sudden death

Poly(lactic acid) (PLA) blended with poly(ζ-caprolactone) (PCL) was prepared with various reactive processing agents. Four isocyanates-lysine triisocyanate (LTI); lysine diisocyanate (LDI); 1,3,5 tris(6 isocyanato-hexyl) 1,3,5 triazinane 2,4,6 trione (Duranate TPA 100); 1,3,5 tris(6 isocyanatohexyl)biuret (Duranate 24A 100) and an industrial epoxide-trimethylolpropane triglycidyl ether (Epiclon 725) were used as reactive processing agents. PLA/PCL blended in the presence of LTI had the highest torque in a mixer test. The test specimens were prepared by injection molding. The mechanical properties, thermal properties, molecular weight, melt viscosity, phase behavior, and morphology were investigated using tensile strength, impact strength, differential scanning calorimetry, melt mass-flow rate measurements, capillary rheometery, gel permeation chromatography, laser scanning confocal microscopy (LSCM), and visco-elasticity atomic force microscopy (VE-AFM). The impact strength increased considerably at 20 wt% PCL. The nominal tensile strain of PLA/PCL blended with LTI increased by 270%. The MFR values of PLA/PCL blends decreased with increasing LTI. Similar results were observed for shear viscosity. LSCM measurements showed that the diameters of PCL were dispersed about 0.4 µm in the presence of LTI. VE-AFM showed that spherical particles with diameters of 50 nm were PCL-rich domain. These results indicate that isocyanate groups of LTI react with both terminal hydroxyl or carboxyl groups of polymers, and the compatibility of PLA/PCL blends improves with LTI by reactive processing. POLYM. ENG. SCI., 48:1359-1368, 2008. © 2008 Society of Plastics Engineers, INTRODUCTION Owing to current environmental issues such as fossil resource depletion and global warming caused by carbon dioxide emission, carbon-neutral materials that have the potential to reduce the consumption of [...]

Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart. Am J Physiol Heart Circ Physiol 278: H388-H396, 2000.--Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily of cytokines, possesses hypertrophic actions and atrial natriuretic peptide (ANP)-producing activity in vitro. The goal of our study is to elucidate whether CT-1 affects the cardiovascular system in vivo. Intravenous injection of CT-1 (4-100 [micro]g/kg) in conscious rats evoked significant declines in blood pressure and reflex increases in heart rate (HR) in a dose-dependent manner. CT-1 induced no significant change in cardiac output (from 260.7 [+ or -] 11.0 to 264.7 [+ or -] 26.6 ml [Multiplied by] [min.sup.-1] [Multiplied by] [kg.sup.-1] P = not significant), which was compatible with the results from isolated perfused rate hearts; HR, change in pressure over time, left ventricular developed pressure, and perfusion pressure were unaffected. Northern blot and RT-PCR analyses revealed that CT-1 increased expression of inducible nitric oxide synthase (iNOS) in lung and aorta but not in heart or liver. Pretreatment with aminoguanidine, a specific iNOS inhibitor, inhibited both iNOS mRNA production and the depressor effect of CT-1. Interestingly, CT-1 increased ventricular expression of ANP and brain natriuretic peptide (BNP). The data demonstrate that CT-1 elicits its hypotensive effect via a nitric oxide-dependent mechanism and that CT-1 induces ANP and BNP mRNA expression in vivo. blood pressure; nitric oxide synthase; natriuretic peptide