Peter B. Colligan

Leptin Attenuates Cardiac Contraction in Rat Ventricular Myocytes: Role of NO

Obesity is commonly associated with impaired myocardial contractile function. However, a direct link between these 2 states has not yet been established. There has been an indication that leptin, the product of the human obesity gene, may play a role in obesity-related metabolic and cardiovascular dysfunctions. The purpose of this study was to determine whether leptin exerts any direct cardiac contractile action that may contribute to altered myocardial function. Ventricular myocytes were isolated from adult male Sprague-Dawley rats. Contractile responses were evaluated by use of video-based edge detection. Contractile properties analyzed in cells electrically stimulated at 0.5 Hz included peak shortening, time to 90% peak shortening, time to 90% relengthening, and fluorescence intensity change. Leptin exhibited a dose-dependent inhibition in myocyte shortening and intracellular Ca2+ change, with maximal inhibitions of 22.4% and 26.2%, respectively. Pretreatment with the NO synthase inhibitor N&ohgr;-nitro-l-arginine methyl ester (L-NAME, 100 &mgr;mol/L) blocked leptin-induced inhibition of both peak shortening and fluorescence intensity change. Leptin also stimulated NO synthase activity in a time- and concentration-dependent manner, as reflected in the dose-related increase in NO accumulation in these cells. Addition of an NO donor (S-nitroso-N-acetyl-penicillamine [SNAP]) to the medium mimicked the effects of leptin administration. In summary, this study demonstrated a direct action of leptin on cardiomyocyte contraction, possibly through an increased NO production. These data suggest that leptin may play a role in obesity-related cardiac contractile dysfunction.

Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide

Panax ginseng is used to enhance stamina and relieve fatigue as well as physical stress. Ginsenoside, the effective component of ginseng, regulates cardiovascular function. This study was to examine the effect of ginsenosides Rb1 and Re on cardiac contractile function at the cellular level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz. Contractile properties analysed included: peak shortening (PS), time‐to‐90%PS (TPS), time‐to‐90% relengthening (TR90), and fluorescence intensity change (ΔFFI). Nitric oxide synthase (NOS) activity was determined by the 3H‐arginine to 3H‐citrulline conversion assay. Both Rb1 and Re exhibited dose‐dependent (1 – 1000 nM) inhibition in PS and ΔFFI, with maximal inhibitions between 20 – 25%. Concurrent application Rb1 and Re did not produce any additive inhibition on peak shortening amplitude (with a maximal inhibition of 24.9±6.1%), compared to Rb1 or Re alone. Pretreatment with the NOS inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 100 μM) abolished the effect of Rb1 and Re. Both Rb1 and Re significantly (P<0.05) stimulated NOS activity concentration‐dependently. This study demonstrated a direct depressant action of ginsenosides on cardiomyocyte contraction, which may be mediated in part through increased NO production.

Direct ortho -palladation of 2-phenyl-2-oxazoline: Crystal structure of Cl2Pd(OCH2CH2NCPh)2 and Cl(PPh3)Pd(OCH2CH2NCC6H4)

Direct ortho -palladation of sterically non-hindered 2-phenyl-2-oxazoline ( 1 ) using Pd(OAc) 2 and AcONa in AcOH provided di-μ-acetatobis-[2-(2-oxazolinyl)phenyl,1-C,3-N]dipalladium(II) ( 3a ) in a yield of 63%. Dimeric complex 3a was converted into the corresponding μ-chloro analog ( 3b ) by the reaction with LiCl in acetone in quantitative yield. Compound 3b was also obtained in 90% yield by the ligand exchange reaction of oxazoline ( 1 ) with dimeric ortho -palladated complex of N , N -dimethylbenzylamine in a AcOH–CHCl 3 mixture at 50°C. The same reaction at room temperature provided the coordination complex dichlorobis-(2-phenyl-2-oxazoline)palladium(II) ( 2 ); the use of toluene in this reaction (50°C) led to the formation of chloro[ N , N -dimethylbenzylamino]-(2-phenyl-2-oxazoline)palladium(II) ( 5 ). Dimer 3b reacted with 2,4-pentadionate and PPh 3 to yield the corresponding mononuclear derivatives 6 and 7 , respectively. The structures of coordination complex 2 and phosphane adduct 7 were confirmed by X-ray diffraction analysis. Compound 2 has a centrosymmetric structure with strictly planar coordination environment of the palladium center and a close above-plane approach of the ortho -CH bond to the metal center. In adduct 7 , both the palladium coordination sphere and palladacycle are nearly planar.

Prenatal ethanol exposure alters ventricular myocyte contractile function in the offspring of rats

Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg2+ supplementation was shown to ameliorate ethanol-induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg2+ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix™ soft-edge system, and intracellular Ca2+ transients were measured as changes in fura-2 fluorescence intensity (ΔFFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR90) associated with a normal ΔFFI and time to PS (TPS). Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR90, and altered the ΔFFI, as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca2+ or stimulating frequency, which were restored by gestational Mg2+ supplementation. These data suggest that although gestational Mg2+ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg2+ supplementation affects cell mechanics itself.

Direct ortho-palladation of 2-phenyl-2-oxazoline: Crystal structure of Cl2Pd(Ph)2 and Cl(PPh3)Pd(C6H4)

Direct ortho -palladation of sterically non-hindered 2-phenyl-2-oxazoline ( 1 ) using Pd(OAc) 2 and AcONa in AcOH provided di-μ-acetatobis-[2-(2-oxazolinyl)phenyl,1-C,3-N]dipalladium(II) ( 3a ) in a yield of 63%. Dimeric complex 3a was converted into the corresponding μ-chloro analog ( 3b ) by the reaction with LiCl in acetone in quantitative yield. Compound 3b was also obtained in 90% yield by the ligand exchange reaction of oxazoline ( 1 ) with dimeric ortho -palladated complex of N , N -dimethylbenzylamine in a AcOH–CHCl 3 mixture at 50°C. The same reaction at room temperature provided the coordination complex dichlorobis-(2-phenyl-2-oxazoline)palladium(II) ( 2 ); the use of toluene in this reaction (50°C) led to the formation of chloro[ N , N -dimethylbenzylamino]-(2-phenyl-2-oxazoline)palladium(II) ( 5 ). Dimer 3b reacted with 2,4-pentadionate and PPh 3 to yield the corresponding mononuclear derivatives 6 and 7 , respectively. The structures of coordination complex 2 and phosphane adduct 7 were confirmed by X-ray diffraction analysis. Compound 2 has a centrosymmetric structure with strictly planar coordination environment of the palladium center and a close above-plane approach of the ortho -CH bond to the metal center. In adduct 7 , both the palladium coordination sphere and palladacycle are nearly planar.

Direct ortho-palladation of 2-phenyl-2-oxazoline

Direct ortho -palladation of sterically non-hindered 2-phenyl-2-oxazoline ( 1 ) using Pd(OAc) 2 and AcONa in AcOH provided di-μ-acetatobis-[2-(2-oxazolinyl)phenyl,1-C,3-N]dipalladium(II) ( 3a ) in a yield of 63%. Dimeric complex 3a was converted into the corresponding μ-chloro analog ( 3b ) by the reaction with LiCl in acetone in quantitative yield. Compound 3b was also obtained in 90% yield by the ligand exchange reaction of oxazoline ( 1 ) with dimeric ortho -palladated complex of N , N -dimethylbenzylamine in a AcOH–CHCl 3 mixture at 50°C. The same reaction at room temperature provided the coordination complex dichlorobis-(2-phenyl-2-oxazoline)palladium(II) ( 2 ); the use of toluene in this reaction (50°C) led to the formation of chloro[ N , N -dimethylbenzylamino]-(2-phenyl-2-oxazoline)palladium(II) ( 5 ). Dimer 3b reacted with 2,4-pentadionate and PPh 3 to yield the corresponding mononuclear derivatives 6 and 7 , respectively. The structures of coordination complex 2 and phosphane adduct 7 were confirmed by X-ray diffraction analysis. Compound 2 has a centrosymmetric structure with strictly planar coordination environment of the palladium center and a close above-plane approach of the ortho -CH bond to the metal center. In adduct 7 , both the palladium coordination sphere and palladacycle are nearly planar.