Abstract-Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age-and gender-related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60°head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (Ϫ10.2Ϯ2 versus Ϫ1.2Ϯ3 mm Hg; Pϭ0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (Pϭ0.02). Upright plasma norepinephrine was lower in women (Pϭ0.02). Women had greater supine high-frequency R-R interval power than men (Pϭ0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (Pϭ0.01), despite higher supine (Pϭ0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness. (Hypertension. 1999;33:1195-1200.)Key Words: sympathetic nervous system Ⅲ norepinephrine Ⅲ spectral analysis Ⅲ hypotension A nalyses of the beat-to-beat variability of cardiac R-R intervals have been used to quantify alterations in autonomic function and predict adverse clinical events. 1,2 Since both age and gender have a profound influence on the risk of cardiovascular disease and death, it is important to understand the effects of healthy aging and gender on autonomic control of cardiovascular function. Previous studies have shown reductions in heart rate (HR) variability with aging 3,4 and increases in high-frequency HR variability in women compared with men. [5][6][7] Since many studies did not rigorously screen subjects to exclude occult cardiovascular disease, it is not known whether abnormalities in short-term autonomic control of HR reflect subclinical cardiovascular disease or whether they represent "normal" age-or gender-related alterations in autonomic function.The effects of age and gender on beat-to-beat blood pressure (BP) dynamics have been less well studied, and it is not known whether changes in the autonomic regulation of beat-to-beat BP are associated with hemodynamic impairment. Therefore, we asked the following questions: (1) Are there specific age-and gender-related alterations in the autonomic control of beat-tobeat BP dynamics in healthy individuals free of cardiovascular disease? (2) If so, what are the hemodynamic consequences of these changes during orthostatic stress?We u...

We have determined whole body protein kinetics, i.e., protein synthesis (PS), breakdown (PB), and net balance (NB) in human subjects in the fasted state and following ingestion of ϳ40 g [moderate protein (MP)], which has been reported to maximize the protein synthetic response or ϳ70 g [higher protein (HP)] protein, more representative of the amount of protein in the dinner of an average American diet. Twenty-three healthy young adults who had performed prior resistance exercise (X-MP or X-HP) or time-matched resting (R-MP or R-HP) were studied during a primed continuous infusion of]phenylalanine and L-[ 2 H2]tyrosine. Subjects were randomly assigned into an exercise (X, n ϭ 12) or resting (R, n ϭ 11) group, and each group was studied at the two levels of dietary protein intake in random order. PS, PB, and NB were expressed as increases above the basal, fasting values (mg·kg lean body mass Ϫ1 ·min Ϫ1 ). Exercise did not significantly affect protein kinetics and blood chemistry. Feeding resulted in positive NB at both levels of protein intake: NB was greater in response to the meal containing HP vs. MP (P Ͻ 0.00001). The greater NB with HP was achieved primarily through a greater reduction in PB and to a lesser extent stimulation of protein synthesis (for all, P Ͻ 0.0001). HP resulted in greater plasma essential amino acid responses (P Ͻ 0.01) vs. MP, with no differences in insulin and glucose responses. In conclusion, whole body net protein balance improves with greater protein intake above that previously suggested to maximally stimulating muscle protein synthesis because of a simultaneous reduction in protein breakdown. essential amino acids; optimal protein intake; protein turnover; stable isotope tracers.THE PRINCIPAL NUTRITIONAL goal of a protein-rich meal is to induce an anabolic state in which protein synthesis exceeds breakdown. Several recent studies, including our own (25), indicate that the maximum acute stimulation of muscle protein synthesis (MPS) occurs with ingestion of ϳ 20 -35 g of high-quality protein (20,25,31) or more specifically 0.24 g·kg body wt Ϫ1 ·meal Ϫ1 in healthy young adults (19). The maximal dose in terms of stimulation of MPS is less than that typically consumed with the dinner meal in the average American diet, which generates a hypothesis that distributing the amount of protein intake throughout the day can more effectively stimulate anabolic response. However, the assertion that there is limited effectiveness of the conventional protein intake with dinner is based on incomplete assessment of the metabolic response of muscle protein. Importantly, the extent of muscle protein anabolism (the anabolic response) is not simply the response of MPS but rather the net balance between the response of protein synthesis and protein breakdown. We recently demonstrated the potential importance of suppression of protein breakdown in response to dietary intake of meals containing two levels of protein totaling either 0.8 or 1.5 g protein·kg Ϫ1 ·day Ϫ1 . We found that at both levels of dietary p...

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.

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BackgroundThe microRNAs have been implicated in the process of cardiac development, cardiac hypertrophy, and heart failure. However, the impact of adult aging on cardiac expression of miRNA clusters, as well as both miRNA guide (miR) and passenger (miR*) strands has not been well established.Methods/ResultsWe explored the expression profile of both miR and miR* in the hearts of young adult versus old mice. We found that 65 miRNAs were differentially expressed in the old versus young adult hearts; approximately half of them were clustered miRNAs that were distributed in 11 miRNA clusters. Each miRNA cluster contained from 2 to as many as 71 miRNA genes. The majority of the clusters displayed similar expression, with most cluster members within a cluster being either increased or decreased together, suggesting that most clusters are likely to be regulated by a common signaling mechanism and that the combined expression of multiple miRNA genes in a cluster could pose an impact on a broad range of targets during aging. We also found age-related changes in the expression of miR*s. The expression of both miR and miR* correlated with that of pri-miRNA transcript over the time course from development and maturation through adult aging. Age-related changes in the expression of Ago1 and Ago2 proteins in the heart were also observed. Transfection assay revealed that both Ago1 and Ago2 synergistically induced miR-21 and miR-21* when the mir-21 plasmid was co-transfected with either.ConclusionThe data revealed age-related changes in the expression of pri-miRNA transcript, Argonaut proteins and both miR and miR* strands. The major changes occurred later in life, from middle to old age. It is likely that the expression of miR and miR* is regulated by both pri-miRNA transcription as well as Ago1 and Ago2 proteins during adult aging.

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Gender-related morphologic and functional differences are important to consider in cardiovascular assessment. Very old rats show significant gender differences in LV size and function. Male rat hearts are larger, thinner and more fibrotic and have indexes of diminished performance. The high prevalence of MR in male rats may play a crucial role in these gender differences.