Beta-adrenergic-mediated vasorelaxation declines with maturation and aging. Available data suggest that impaired stimulatory G-protein function could explain this deficit. We have previously found a loss of cholera toxin (CT)-stimulated adenosine diphosphate (ADP) ribosylation with age in rat aortic membrane preparations, without evidence for loss of the stimulatory alpha subunit of G protein (...

BACKGROUND Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. METHODS Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extra...

Although it is hypothesized that there is abnormal motor inhibition in patients with dystonia, the question remains as to whether the mechanism related to motor inhibition is specifically impaired. The objective of the present study was to clarify the possible abnormalities of the mechanisms underlying voluntary muscle relaxation during motor preparation and execution in patients with writer's ...

BACKGROUND The management of sick newborn infants who have sustained a hypoxic insult is a common clinical problem but relatively little is known about the recovery process. The aim of this study was to investigate this process in newborn piglets. METHODS Thirty five newborn piglets were exposed to chronic hypobaric hypoxia for three days, either from birth, three or 14 days of age, and were ...

Antioxidants improve endothelial function in hypercholesterolemia (HC); however, whether this includes improvement of the vascular smooth muscle response to NO is unknown. NO relaxes arteries, in part, by stimulating Ca(2+) uptake via sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) in aortic smooth muscle, and HC impairs SERCA function and the response to NO. HC induces oxidative stress, whic...

Vascular responses of human intramyocardial small arteries were examined in vitro to assess the influence of atherosclerosis and risk factors for coronary artery disease on endothelium-dependent relaxation. Recipient hearts were obtained from patients with ischemic ( n = 14) and nonischemic ( n = 13) cardiomyopathy undergoing heart transplantation. Small intramyocardial coronary arteries (mean ...

Because nitric oxide (NO) regulates cardiac and vessel contraction, we compared the expression and activity of the endothelial NO synthase (eNOS) and caveolin, which tonically inhibits eNOS in normal and hypertrophic cardiomyopathic hearts. NOS activity (L-[(3)H]citrulline formation), eNOS immunostaining, and caveolin abundance were measured in heart tissue of 23 mongrel dogs before and at 3 an...

It is not known whether angiotensin II type 1 receptor antagonists can influence the function and morphology of small arteries in renal failure. We investigated the effect of 8-week losartan therapy (20 mg/kg per day) on isolated mesenteric resistance arteries by wire and pressure myographs in 5/6 nephrectomized rats. Plasma urea nitrogen was elevated 1.6-fold after nephrectomy, and ventricular...

INTRODUCTION Frequency-dependent acceleration of relaxation (FDAR) ensures appropriate ventricular filling at high heart rates and results from accelerated sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) activity independent of calcium removal from the cell. Because lipopolysaccharide (LPS) challenge may induce aberrations in calcium trafficking and protein phosphorylation, we tested ...

BACKGROUND Impaired relaxation is a cardinal feature of senescent myocardial dysfunction. Recently, adenoviral gene transfer of parvalbumin, a small calcium-buffering protein found exclusively in skeletal muscle and neurons, has been shown to improve cardiomyocyte relaxation in disease models of diastolic dysfunction. The goal of this study was to investigate whether parvalbumin gene transfer c...