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Biomedical subjects

S M Schanberg

Publications and source records attributed to S M Schanberg.

At least 19 recordsLinked to original sources
PubMed1992

Accentuated vagal antagonism of beta-adrenergic effects on ventricular repolarization. Evidence of weaker antagonism in hostile type A men.

BACKGROUND: Prior research has suggested a weaker parasympathetic antagonism of sympathetic effects on the heart in type A (coronary-prone) men. To confirm this phenomenon and extend our understanding of it, we investigated the effects of prior muscarinic blockade on the electrocardiogram T wave and other cardiovascular and neuroendocrine responses to isoproterenol in type A and type B (non-coronary-prone) men. METHODS AND RESULTS: Responses to two 5-minute intravenous isoproterenol infusions (0.01 micrograms/kg/min and 0.02 micrograms/kg/min) were evaluated in six type A and six type B men after pretreatment with either dextrose placebo or atropine (1.2 mg). Atropine significantly potentiated T wave attenuation in the recovery period after isoproterenol infusion (0.30 +/- 0.07 mV) compared with placebo (0.54 +/- 0.09 mV, p less than 0.001). Atropine also potentiated the heart rate increase to isoproterenol (39 +/- 3 beats per minute versus 20 +/- 2 beats per minute after placebo). Atropine enhanced decreases in systolic, diastolic, and mean arterial pressures as well as pulse pressure to isoproterenol. Atropine enhancement of many of these responses was increased among subjects with high scores on various hostility/anger scales. Isoproterenol alone produced greater T wave attenuation in type A than in type B men. However, atropine enhancement of T wave attenuation and blood pressure falls by isoproterenol was present only in type B men. CONCLUSIONS: These findings indicate that there is accentuated parasympathetic antagonism of T wave attenuation and blood pressure responses induced by beta-adrenergic stimulation. Relative weakness of this antagonism of sympathetic effects on the heart in hostile type A individuals may contribute to their higher coronary disease risk.

Adult↗
PubMed1991

Further evidence for the hypothesis that beta-endorphin mediates maternal deprivation effects.

Lung DNA synthesis was examined in 9-day-old rat pups following a 2-hour separation from their mothers (maternal deprivation), and compared to that of pups placed with a nipple ligated dam (food deprivation) or a lactating dam (control). Maternally deprived pups consistently showed a significant reduction in lung DNA synthesis which was not attributable to food deprivation. Central administration of naloxone prevented the decrease in DNA synthesis observed after maternal deprivation but did not inhibit the reductions in lung DNA synthesis seen two hours after sc administration of isoproterenol, suggesting that DNA response to maternal deprivation is a specific opioid receptor mediated event. These results are consistent with previous reports from our laboratory indicating that CNS beta-endorphin may mediate many of the biological alterations observed following maternal deprivation in neonatal rats.

Animals↗
PubMed1991

Effects of central administration of beta-endorphin on brain and liver DNA synthesis in preweanling rats.

We have previously shown that central administration of beta-endorphin results in a reduction of ornithine decarboxylase activity. Ornithine decarboxylase catalyses the rate-limiting step in the biosynthesis of the polyamines putrescine, spermidine and spermine, thought to modulate nucleic acid synthesis. The present study examines the effects of intracisternal injection of beta-endorphin on brain and liver DNA synthesis in preweanling rats. In six-day-old rats, beta-endorphin (0.75 micrograms/g brain wt) produced approximately a 70% inhibition in brain and liver DNA synthesis 1 h after injection, and values were still subnormal in both tissues 10 h later. Subcutaneous administration of beta-endorphin did not alter liver DNA synthesis. Thus, it is most likely that the suppressed liver DNA synthesis observed in animals given beta-endorphin intracisternally is mediated by central mechanisms. Co-administration of naloxone plus beta-endorphin intracisternally prevented the response, indicating an opioid receptor-mediated phenomenon. Naloxone alone caused small but significant increases in brain and liver DNA synthesis, suggesting a tonic influence on tissue DNA by endogenous opioids in the CNS. Acute inhibition of ornithine decarboxylase activity by alpha-difluoromethylornithine did not alter DNA synthesis, indicating that the decreases in DNA synthesis induced by beta-endorphin are unrelated to the ornithine decarboxylase/polyamine system. The effect appears to be restricted to early development as no significant changes in DNA synthesis were obtained in 20-day-old animals. The results from these studies indicate that CNS beta-endorphin has the ability to influence DNA synthesis in central as well as in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Tactile-kinesthetic stimulation effects on sympathetic and adrenocortical function in preterm infants.

The purpose of our study was to investigate the neuroendocrine response in preterm infants to a pattern of tactile-kinesthetic stimulation that facilitates their growth and development. Preterm infants (mean gestational age 30 weeks, mean birth weight 1176 gm) received normal nursery care or tactile-kinesthetic stimulation for three 15-minute periods at the start of three consecutive hours each day for 10 days. On day 1 and day 10 of the study, a 24-hour urine sample was collected for norepinephrine, epinephrine, dopamine, cortisol, and creatinine assay and a blood sample was taken by heel stick for cortisol and growth hormone assay. Urine norepinephrine and epinephrine values increased significantly only in the stimulated babies. Urine dopamine and cortisol values increased in both groups, and serum growth hormone decreased in both groups. Individual differences in urine norepinephrine, epinephrine, dopamine, and cortisol values were highly stable across the 10 days despite a 10-fold range of values among the infants. The results of this study suggest that tactile-kinesthetic stimulation of preterm infants has fairly specific effects on maturation and/or activity of the sympathetic nervous system. In addition, this study has defined catecholamine and cortisol secretion across gestational age in normal preterm infants. Finally, these data suggest that highly stable individual levels of catecholamine and cortisol secretion are established by birth in humans.

Creatinine↗
PubMed1991

Effect of central administration of beta-endorphin on lung ornithine decarboxylase activity in developing rats.

Results from a number of studies suggest a role for endogenous opioids in the regulation of lung development and function. Although it is not known which opioid peptides are involved in these processes, accumulated evidence suggests a prominent role for beta-endorphin (BE). Our study examines the effect of BE on lung ornithine decarboxylase (ODC) activity in preweanling rats. ODC catalyzes the rate-limiting step in the synthesis of the polyamines spermidine and spermine, key regulators of cell growth, multiplication, and differentiation. Central (but not peripheral) administration of BE reduced lung ODC activity by as much as 80% in the 6-d-old rat. Significant decreases in ODC activity were seen at doses of BE as low as 0.5 micrograms/g brain wt. In contrast to the reductions in ODC activity, plasma levels of corticosterone in animals administered BE were approximately five times higher than those seen in control animals. BE's actions on ODC activity and plasma corticosterone levels were prevented by naloxone or naltrexone, indicating that both responses are mediated by opioid receptors. Studies of ODC kinetics showed a profound reduction in Vmax (70% below control values), but no change in Km. The effect was observed only during the first 2 wk of postnatal age, a period of time in lung maturation that is characterized by active alveolarization. Because changes in ODC levels during early postnatal life are associated with perturbations in tissue growth and/or function, the data suggest that CNS BE may influence lung maturation through an indirect action that may involve glucocorticoids.

Age Factors↗
PubMed1991

Alterations in cardiovascular responsiveness and adrenoceptor binding during catecholamine infusion hypertension in rats.

Chronic continuous infusion of norepinephrine in rats causes alterations in biochemical and physiologic responses of the cardiovascular system and in cardiovascular adrenoceptor number. The response of cardiac and aortic ornithine decarboxylase (ODC) activity to stimulation by norepinephrine was decreased in rats receiving norepinephrine infusion. These responses are due to stimulation of beta- and alpha-adrenergic receptors, respectively. Additionally, there was reduced stimulation of aortic ODC activity by angiotensin II and vasopressin. The cardiac ODC response to angiotensin II was decreased, but the response to vasopressin was not affected. The decreased ODC response is accompanied by decreased pressor responses to the alpha-adrenergic agonist phenylephrine. Decreased numbers of alpha- and beta-adrenoceptor binding sites (as measured by the binding of [3H]prazosin and [125I]pindolol) might mediate, in part, the altered responses to adrenergic agonists. The decreased cardiovascular responsiveness measured in these animals after several days of norepinephrine infusion hypertension contrasts with the increased responses found in most other forms of hypertension. This provides a useful model in which to examine the consequences of prolonged adrenergic receptor stimulation.

Angiotensin II↗
PubMed1978

Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated during development with 5,7-dihydroxytryptamine.

The serotonin precursor, 5-hydroxytryptophan (5-HTP), can induce a behavioral syndrome characterized by rigidity, splayed feet, tremor, head weaving, salivation and forepaw treading. This response to 5-HTP was markedly potentiated in adult rats treated intracisternally with 5,7-dihydroxytryptamine (5,7-DHT) during development. Prevention of the 5,7-DHT-induced reduction of brain norepinephrine with pargyline or desipramine did not diminish the potentiation of 5-HTP, suggesting that noradrenergic fibers are not contributing to the altered 5-HTP response. It was also found that treatments with 5,7-DHT potentiated the release of prolactin and the disruption of responding in a fixed-ratio operant task induced by 5-HTP. Other experiments indicated that 5,7-DHT treatments potentiated 5-HTP without affecting the action of L-dihydroxyphenylalanine. In addition, administration of the decarboxylase inhibitor, R0-4-4602, at a dose that inhibits enzyme activity in brain, blocked the 5-HTP-induced behavioral syndrome in 5,7-DHT-treated rats, indicating that 5-HTP must be converted to serotonin for 5-HTP to alter behavior. Thus, the present studies indicate that destruction of serotonergic fibers during development can produce permanent changes in central serotonergic mechanisms.

5,7-Dihydroxytryptamine↗
PubMed1978

Selective depression of serum growth hormone during maternal deprivation in rat pups.

Maternal deprivation was associated with a decline in immunoreactive growth hormone in the serum of rat pups. Pups that were returned to the mother showed a rapid reversal in this deprivation-induced decrease. The change in growth hormone concentration was not accompanied by changes in the concentrations of prolactin, thyrotropin, or corticosterone in the serum, but were correlated with alteration in the activity of ornithine decarboxylase in the brain. Treatment of neonatal rat pups with cyprohepatadine, a serotonin antagonist that suppresses growth hormone secretion, resulted in a significant decline in both serum growth hormone concentration and brain ornithine decarboxylase activity. These findings suggest that maternal deprivation elicits a specific suppression of growth hormone release which mediates the decrease in ornithine decarboxylase activity. The study is consistent with clinical findings of impaired growth hormone "responsitivity" in human maternal deprivation syndrome.

Animals↗
PubMed1978

Maternal behavior as a regulator of polyamine biosynthesis in brain and heart of the developing rat pup.

Rat pups removed from the mother and placed in a warm incubator for 1 hour or more show a 50 percent reduction in ornithine decarboxylase activity in the brain and heart. The decline is not caused by lack of nutrition. Instead, these studies suggest that active maternal behavior is necessary to maintain normal polyamine metabolism in brain and heart of the pup during development.

Adrenalectomy↗
PubMed1978

Type A behavior pattern and coronary atherosclerosis.

Previous research has demonstrated an increased rate of clinical coronary heart disease (CHD) events among people who exhibit a "coronary prone" (Type A) behavior pattern. This study was undertaken to determine whether the association between behavior pattern Type A and CHD might be extended beyond clinical CHD events to include also the coronary atherosclerotic process. In addition to usual clinical evaluation, 156 consecutive patients referred for diagnostic coronary angiography were independently assessed on the basis of a structured interview and assigned a rating of Type A, Type B, or Type X (indeterminate). Traditional physiologic factors--age, sex, cholesterol and cigarette smoking--were found to correlate with atherosclerotic disease. Type A patients were found in increasing proportions among groups of patients with coronary occlusions of moderate to severe degree compared with patients with only mild occlusions. This increasing proportion of Type A patients with increasing disease severity remained significant, even when age, sex, blood pressure, serum cholesterol level and cigarette smoking history were all simultaneously covaried. These findings suggest that, independently of traditional risk factors, behavior pattern Type A may contribute to the risk of clinical CHD events via effects on the atherosclerotic process.

Adolescent↗