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Biomedical subjects

S L Mader

Publications and source records attributed to S L Mader.

14 recordsLinked to original sources
PubMed1992

Influence of animal age on the beta-adrenergic system in cultured rat aortic and mesenteric artery smooth muscle cells.

It has previously been reported that aortic smooth muscle cells cultured from old rats have a marked decline in beta-adrenergic stimulated cAMP accumulation. We wished to confirm this observation and determine whether this decline was secondary to loss of beta-adrenergic receptors (BAR). Primary cultures of aortic and mesenteric artery smooth muscle cells were obtained by enzymatic digestion from young and old male Fischer 344 rats. In aortic cells from old animals, there was a decline in beta-adrenergic receptor density and a rightward shift in the dose response curve to isoproterenol without a change in maximal cAMP accumulation. In mesenteric artery cells, there were no age changes in these parameters. Beta-adrenergic receptor subtype distribution was determined and was similar between all age groups and vessel types. These findings differ from whole tissue studies and suggest that cultured smooth muscle cells have limitations as a model for the aging adrenergic system.

Aging↗
PubMed1992

Functional antagonism between YY1 and the serum response factor.

The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated by the serum response element (SRE). The SRE shares homology with the muscle regulatory element (MRE) of the skeletal alpha-actin promoter. It is not known how these elements respond to proliferative and cell-type-specific signals, but the response appears to involve the binding of the serum response factor (SRF) and other proteins. Here, we report that YY1, a multifunctional transcription factor, binds to SRE and MRE sequences in vitro. The methylation interference footprint of YY1 overlaps with that of the SRF, and YY1 competes with the SRF for binding to these DNA elements. Overexpression of YY1 repressed serum-inducible and basal expression from the c-fos promoter and repressed basal expression from the skeletal alpha-actin promoter. YY1 also repressed expression from the individual SRE and MRE sequences upstream from a TATA element. Unlike that of YY1, SRF overexpression alone did not influence the transcriptional activity of the target sequence, but SRF overexpression could reverse YY1-mediated trans repression. These data suggest that YY1 and the SRF have antagonistic functions in vivo.

Animals↗
PubMed1991

Chronic hypoxia increases beta-adrenergic receptor density in the lungs of young and old rats.

To test the hypothesis that the ability to regulate beta-adrenergic receptor (BAR) density in response to chronic hypoxic stress is impaired by aging, we measured BAR density in the lungs of young (age 3 months) and aged (age 20 months) rats exposed to hypobaric hypoxia (1/2 atm) for 3 weeks. BAR density increased by 63% in the lungs of both young and aged rats exposed to chronic hypoxia. Lung BAR density was unaffected by aging, independent of hypoxic conditions. We conclude that the ability to respond to chronic hypoxic stress with increased lung BAR density is unaffected by aging in rats.

Adaptation, Physiological↗
PubMed1991

Effect of age and hypoxia on beta-adrenergic receptors in rat heart.

Previous reports suggest that hypoxia downregulates cardiac beta-adrenergic receptors from young rats. Because aging alters response to stress, we hypothesized an age-related alteration in the response to hypoxia. Male Fischer-344 rats, aged 3 and 20 mo, were divided into control and hypoxic groups. The hypoxic rats were exposed to hypobaric hypoxia (0.5 atm) for 3 wk. After hypoxic exposure, body weight decreased, hematocrit increased, right ventricular weight increased, and left ventricular weight decreased in all animals. beta-Adrenergic receptor density declined after hypoxic exposure in the young but not in the older animals, a change that was confined to the left ventricle. beta-Adrenergic receptor density in the right ventricle was significantly lower in the older animals than in the young animals. Plasma catecholamines (norepinephrine, epinephrine) drawn after the animals were killed (stress levels) decreased in young rats and increased in old rats after the exposure to hypoxia. Hypoxia is a useful physiological stress that elucidates age-related changes in cardiac beta-adrenergic receptor and catecholamine regulation that have not previously been described.

Aging↗
PubMed1991

Beta-adrenergic function in aging. Basic mechanisms and clinical implications.

Catecholamines have an important endocrine and neuroendocrine role in mediating a variety of autonomic functions. One consequence of normal aging, in particular in the cardiovascular system, is a decline in beta-adrenergic function associated with an alteration in responsiveness to beta-adrenergic therapy. The intrinsic ability for muscle contractility or relaxation is maintained with age and there appears to be an alteration in the process linking the receptor with the contractile or relaxation mechanisms. In rats, beta-adrenergic receptor density decreases with age in adipose tissues and most brain areas, is unchanged in lymphocytes, heart and lung, and increases in the liver. In humans, there are no receptor changes with age in either lymphocytes or brain. In contrast, the number of high-affinity receptors (or coupled receptors) decreases with age in most tissues. In addition, there is a decrease in membrane adenylate cyclase activity or cellular production of cyclic adenosine monophosphate (adenosine 3',5'-cyclic phosphate; cAMP). Plasma noradrenaline (norepinephrine) concentration increases with age. The reduced receptor number in some tissues (down-regulation), the reduced high-affinity receptors and the reduced hormone-stimulated adenylate cyclase activity with age suggests receptor desensitisation to increased plasma noradrenaline concentration. The inability of older animals to desensitise to beta-adrenergic agonists further supports this hypothesis. However, there is an additional post-receptor reduction in catalytic unit activity with age independent of desensitisation. Medications directed at the beta-adrenergic system are commonly used in the elderly. Many of the data on the impact of age on clinical responses are conflicting or unavailable. Concomitant disease, functional status, nutritional state and polypharmacy may play an even greater role than age. However, the available data can be used to guide the selection of therapy, anticipate side effects, and predict potential interactions with other medications and diseases.

Aged↗
PubMed1990

Diminished adrenal steroidogenic activity in aging rats: new evidence from adrenal cells cultured from young and aged normal and hypoxic animals.

Adrenal cells from 2-6-month-old young rats (Y cells) and from 19-25-month-old aged male rats (O cells) were adapted to primary monolayer culture. The cultures of Y and O cells appeared to be primarily epithelial and rounded up in response to stimulation with adrenocorticotropic hormone (ACTH). The general morphology of O cells was comparable to that observed in Y cells except for the presence of lipofuscin-like granules, a cellular marker of aging, in O cells, but not in Y cells. ACTH-stimulated steroid production by O cells was 52% lower than that by Y cells. Exposure of intact young rats to hypoxia (0.5 atmosphere) for 21 days prior to sacrifice and culture resulted in a 122% increase of ACTH-stimulated adrenal steroidogenic activity in the cultured cells, but this effect was not observed in adrenal cells cultured from hypoxic aged rats. The results suggest that there is an age-related diminution in rat adrenal steroidogenic capacity in response to ACTH stimulation in culture derived from Y and O animals; hypoxic stress magnifies this difference.

Adrenal Cortex↗
PubMed1990

Hyperadrenergic orthostatic intolerance as a result of postpartum blood loss.

This article describes a young women in whom orthostatic intolerance developed as a result of protracted postpartum vaginal bleeding. The cardiovascular abnormalities were unresponsive to usual treatment measures, and she required combination therapy directed at increasing plasma volume and decreasing sympathetic nervous system activity. After resolution of her symptoms, the patient required no long-term therapy. Chronic blood loss has not been reported as a cause of this syndrome.

Adult↗
PubMed1989

Orthostatic hypotension.

Orthostatic hypotension is a rare finding in healthy elderly subjects, but is a common clinical problem in older patients. Assessment of symptoms and the blood pressure response to standing is an important part of the initial evaluation and follow-up of geriatric patients. Generally, more than one cause will be identified, and these patients respond to simple treatment measures. Identification and treatment of this disorder will improve function and independence in this population.

Aged↗
PubMed1989

Effect of age on acute regulation of beta-adrenergic responses in mononuclear leukocytes.

We studied the acute regulation of beta-adrenergic receptors and cAMP production in mononuclear leukocytes from young and old human subjects. After one hour of supine rest, healthy young and elderly subjects had similar beta-adrenergic receptor density and cAMP responses to isoproterenol. After 10 min of standing, beta-adrenergic receptor density and cAMP response increased in the young subjects. Elderly subjects had a similar increase in cAMP responses after standing, but no change in beta-adrenergic receptor density. Lymphocyte subsets and percent monocytes were not altered by age or posture, suggesting that this was not an artifact of changes in cell populations. Incubation in vitro of cells from both groups with catecholamines, at concentrations comparable to those achieved in plasma after standing, resulted in enhanced isoproterenol-mediated cAMP responses, but no change in beta-adrenergic receptor density. These data suggest that acute regulation of adrenergic signaling is affected by age, mediated in part by catecholamines, and may be relevant in the study of acute cardiovascular regulation.

Adult↗
PubMed1989

Effect of timing and number of baseline blood pressure determinations on postural blood pressure response.

We hypothesized that the blood pressure response to standing may depend on the method of establishing baseline blood pressure. Three hundred elderly subjects previously completed a postural blood pressure protocol with three supine baseline blood pressure readings obtained two minutes apart prior to standing. Comparison of the readings showed a significant drop between the first and the second (P less than .001) but not between the second and third supine systolic blood pressures. The difference between the first supine systolic blood pressure and the one minute standing blood pressure was significantly greater than that between the third supine systolic blood pressure and the one minute standing blood pressure (P less than .001). A second group was prospectively studied to determine whether the change in blood pressure after standing was greater if only a single baseline reading was taken rather than multiple readings, and whether the decline in blood pressure over three readings was related to duration supine or to the number of blood pressures taken. This group also demonstrated a decline in systolic blood pressure with three serial readings. We conclude that supine blood pressure declines significantly between the first and second readings taken two minutes apart and is secondary to the repetition of readings and not the duration supine. However, this change in supine blood pressure does not significantly alter the blood pressure response to standing. Thus, it appears that a single baseline supine blood pressure measurement is adequate for determining the postural blood pressure response, and that pooling of multiple baseline readings may not be appropriate.

Aged↗
PubMed1989

Aging and postural hypotension. An update.

Postural hypotension is a common clinical problem in elderly patients. Reported studies have investigated the epidemiology and mechanisms of this disorder. However, many of these data are based on subjects with diseases and medications also known to cause this disorder, which confuses the relative contributions of normal aging, disease, and medication effects. This review critically evaluates published studies on measurement, epidemiology, and mechanisms of postural hypotension in screened and unscreened elderly populations. Pertinent age-related changes in physiology and the relationship of postural hypotension in the elderly to other models of postural hypotension are reviewed. Areas of current and future research are outlined.

Aged↗
PubMed1989

Effects of meals and time of day on postural blood pressure responses in young and elderly subjects.

Previous data suggest that postural and postprandial hypotension are common in elderly subjects. This study evaluated the effect of age, meals, and time of day on supine and standing blood pressure (BP) and heart rate in healthy young and elderly subjects. A postural BP protocol was performed on 10 young and 16 elderly subjects during an overnight stay. The protocol included first morning and postprandial readings. The systolic and diastolic BP responses to standing were not significantly different between the two groups and were not affected by time of day. Postprandial recumbent BPs declined significantly only in the older subjects. There was no effect of meals on the BP response to standing. We conclude that healthy elderly subjects have a postprandial decline in BP even when supine. However, the BP response to standing is similar in young and elderly subjects and is not impaired by overnight rest or meals. This suggests that the regulation of BP after meals and with standing may be different.

Adult↗
PubMed1988

Effect of age and posture on human lymphocyte adenylate cyclase activity.

1. A number of age-related changes have been reported in the catecholamine-adrenoceptor-adenylate cyclase system. Most of the data available on these alterations come from resting subjects; the response to acute stress may provide additional insights into the age effect on these responses. 2. We measured supine and 10 min upright plasma noradrenaline and lymphocyte adenylate cyclase activity in ten healthy elderly subjects (age 66-80 years) and seven healthy young subjects (age 27-34 years). 3. Isoprenaline stimulation of lymphocyte adenylate cyclase activity was not significantly different between supine and upright positions or between elderly and young subjects. There was a marked increase in forskolin-stimulated adenylate cyclase activity in the upright posture in both elderly and young subjects. The increment over supine levels was 70% in the elderly (P less than 0.025) and 73% in the young (P less than 0.05). This enhanced forskolin activity was not seen in two young subjects who became syncopal. 4. These data suggest that enhanced forskolin-stimulated adenylate cyclase activity occurs after 10 min of upright posture in both elderly and young subjects, and may be relevant to immediate blood pressure regulation. We were unable to demonstrate any age-related differences in these acute adrenergic responses.

Adenylyl Cyclases↗