Cardiac dysfunction occurs in the HIV-1 transgenic mouse treated with zidovudine.

Cardiomyopathy in AIDS is an increasingly important clinical problem. Mechanisms of AIDS cardiomyopathy were explored using AIDS transgenic mice that express replication-incompetent HIV-1 (NL4-3delta gag/pol). Transgenic and FVB/n mice (n = 3 to 6 per cohort) received water ad libitum with and without zidovudine (3'-azido-2',3'-deoxythymidine; AZT; 0.

The effect of isoproterenol on phospholamban-deficient mouse hearts with altered thyroid conditions.

The aim of the present study was to determine the effects of beta -adrenergic stimulation in wild-type and phospholamban-deficient mouse hearts with altered thyroid conditions. Hypothyroidism was associated with significant decreases in heart/body weight ratio in wild-type and phospholamban-deficient mice, whereas hyperthyroidism was associated with significant increases in heart/body weight ratio in both groups. Hypothyroid hearts of wild-type and phospholamban-deficient mice exhibited similar increases in beta -myosin heavy chain protein levels and decreases in alpha -myosin heavy chain protein levels.

Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart.

It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo.

Protection against hypoxia-reoxygenation in the absence of poly (ADP-ribose) synthetase in isolated working hearts.

Peroxynitrite and hydroxyl radical are reactive oxidants produced during myocardial reperfusion injury. They have been shown to induce dysfunction in cardiac myocytes, in part, via the activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). These oxidants can trigger DNA single strand breakage, which triggers PARS activation, resulting in cellular NAD+ and ATP depletion and cytotoxicity.

Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts.

Cardiac hypertrophy and heart failure are known to be associated with a reduction in Ca2+-ATPase pump levels of the sarcoplasmic reticulum (SR). To determine whether, and to what extent, alterations in Ca2+ pump numbers can affect contraction and relaxation parameters of the heart, we have overexpressed the cardiac SR Ca2+-ATPase specifically in the mouse heart using the alpha-myosin heavy chain promoter. Analysis of 2 independent transgenic lines demonstrated that sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA2a) mRNA levels were increased 3.