Biomedical subjects

C M Kuhn

Publications and source records attributed to C M Kuhn.

At least 55 records · Page 3Linked to original sources

PubMed1992

Effect of ether stress on growth hormone during development in the neonatal rat.

Stress in adult rats causes an inhibition of growth hormone (GH) secretion which might be mediated by corticotropin-releasing factor (CRF). The response of neonates to stress differs from that observed in adults, including changes in GH secretion that are independent of CRF. The present study examines the effects of ether exposure, a stress known to elicit CRF release, on serum GH in the neonatal period. Preliminary experiments indicated that ether elicits increases in serum adrenocorticotropic hormone and corticosterone, and that the latter response is blocked by pretreatment with dexamethasone. Corticosterone was measured as an indicator of hypothalamo-pituitary-adrenal (HPA) axis stimulation for subsequent studies. Rat pups of 5, 8, 10, 15, 18 or 30 days were divided into three groups. Baseline animals were taken for decapitation directly from the mother. Ether animals were exposed to ether fumes for 1 min, returned to the mother after a brief recovery period, and killed 30 min later. Handled control animals were removed from the mother briefly, returned, and similarly killed at 30 min. Blood was assayed for GH and corticosterone. Handling itself stimulated both GH and corticosterone on postnatal days 10 and 15 and suppressed GH and corticosterone on days 5 and 30. Ether significantly lowered GH and increased corticosterone when compared to this handling control from day 8 to 18, but values in ether-treated animals were different from baseline animals only at 5 and 30 days of age. These results indicate that ether stress produces a mild decrease in GH by day 5 postnatally and throughout the neonatal period which is only apparent in relation to 'handled' controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

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↗

PubMed1992

Mu- and kappa-opiate receptor control of prolactin secretion in rats: ontogeny and interaction with serotonin.

The present study explores developmental changes in mu- and kappa-opiate receptor control of PRL secretion. The ontogeny of mu- and kappa-receptor function was determined by assessing the PRL response to the mu-agonist sufentanil (SUF) and the kappa-agonist U50488 in 5-, 10-, 15-, 20-, and 60-day-old rats. Both mu- and kappa-agonists stimulated PRL secretion at all ages. The selectivity of the mu- and kappa-agonists was confirmed by selective blockade with their respective antagonists (beta-funaltrexamine and nor-binaltorphimine). Serotonin mediation of opiate-induced changes in PRL secretion was explored across ontogeny by testing cyproheptadine (CYPRO) blockade of agonist responses in 5-, 10-, 20-, and 60-day-old rats. CYPRO attenuated the PRL response to the mu-agonist SUF in 20- and 60-day-old rats, but not in the 5- or 10-day-old pups. CYPRO did not block the kappa-agonist U50488 at any age. Similarly, pretreatment with parachlorophenylalaine lowered the PRL response to SUF in 60-day-old rats, but not in 10-day-old rats. These results support previous reports of a serotonin-mediated mu control of PRL secretion that develops by day 20 and a kappa control of PRL secretion that is independent of serotonin at all ages. These findings also suggest that a previously reported serotonin-independent mu-receptor-mediated control of PRL secretion can be stimulated early in ontogeny.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1992

Corticosterone hypersecretion in preweanling rats exposed neonatally to trimethyltin.

Developmental neurotoxicity may be influenced by effects of a compound on endocrine function. Here we report that developmental exposure to TMT increases the corticosterone (CS) response to stress in developing rat pups. Long-Evans rat pups were injected i.p. with either 6 mg/kg TMT hydroxide (in 10 microliters/g BW NaCl) or vehicle on Postnatal Day 5 (PND5) or 10 and were then tested for their CS response to restraint stress on PND12, 16, or 20. In the stress test, pups were maternally deprived in individual compartments of an incubator for 24 hr, and then blood sampled by decapitation either immediately (basal), or 30, 60 or 90 min after the onset of a 15-min period of restraint in a wire-mesh holder. Regardless of TMT exposure or age of testing, this procedure produced a peak in plasma CS at 30 min which then recovered to basal levels by 90 min. TMT exposure on PND5 (Experiment 1) resulted in CS hypersecretion relative to vehicle-injected controls on PND12 and 16 but not PND20. TMT exposure on PND10 (Experiment 2) had no effect at PND12 but elevated CS over vehicle controls at PND16 and 20. PND15 exposure to TMT resulted in CS hypersecretion in pups tested on PND20. Neonatal organotin exposure appears to alter CS secretion in a manner that is influenced by age of exposure and age of testing.

Animals↗

PubMed1991

Chronic cocaine administration sensitizes behavioral but not neuroendocrine responses.

Many behavioral responses to cocaine become progressively exaggerated with chronic treatment. Most studies have focused on cocaine-induced locomotor stimulation and changes in the dopamine projection systems which mediate these actions. However, it is not clear if a uniform 'sensitization' develops in all dopamine systems during chronic stimulant administration. To test this possibility the neuroendocrine actions of cocaine which are mediated, in part, by hypothalamic dopamine neurons were evaluated after chronic cocaine administration. Treatment of rats with cocaine (15 mg/kg, 2x/day) markedly enhanced the locomotor response to cocaine after 3 and 7 days of chronic administration. In contrast, neither the stimulation of adrenocorticotropic hormone (ACTH)/corticosterone (CS) secretion nor the slight inhibition of prolactin caused by acute cocaine administration changed, although a small elevation of basal corticosterone secretion was observed after 7 days. These findings suggest that the marked sensitization observed in other dopamine systems does not occur in the hypothalamic dopamine neurons thought to mediate the neuroendocrine responses to cocaine during chronic administration, despite recently described commonalities in uptake and autoreceptor functions in these dopamine cell populations. This contrast suggests a role for long loop feedback systems unique to telencephalic dopamine systems or region-specific neurochemical adaptations in cocaine sensitization.

Adrenocorticotropic Hormone↗

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

Stress reactivity and exercise training in premenopausal and postmenopausal women.

Examined the influence of ovarian function on psychophysiological stress responses and determined if aerobic exercise reduced stress reactivity. Fifty premenopausal and postmenopausal women initially were subjected to a public speaking task and an ice-on-the-forehead procedure, during which time their blood pressure and heart rate were monitored and continuous blood samples were obtained. Subjects also underwent aerobic fitness evaluations with a maximum-exercise treadmill test. Subjects were then randomly assigned to a 12-week exercise program of either aerobic exercise (e.g., walking and jogging at a prescribed exercise intensity) or non-aerobic strength and flexibility training and were then reevaluated. Results indicated that postmenopausal women exhibited lower resting epinephrine levels but greater epinephrine reactivity to the speaking task compared to the premenopausal women. There were no differences between premenopausal and postmenopausal women with respect to cardiovascular or catecholamine responses during the cold challenge. Premenopausal and postmenopausal women also achieved comparable improvements in aerobic fitness. However, results of the mental stress testing were complex and provided only partial support for the role of aerobic exercise in reducing stress responses.

Arousal↗

PubMed1991

Ontogeny of mu- and kappa-opiate receptor control of the hypothalamo-pituitary-adrenal axis in rats.

The purpose of the present study was to determine the relative ontogeny of mu- and kappa-opiate receptor control of the hypothalamo-pituitary-adrenal (HPA) axis in rats. The ability of the mu-agonist morphine and the kappa-agonist U-50,488 to stimulate the HPA axis was determined by evaluating ACTH and corticosterone (CS) secretion in developing rat pups. Morphine elicited marked rises in both ACTH and CS secretion in 10-day-old rats, and these increases were maximal from 30-60 min after drug administration. Both morphine and U50,488H caused a dose-related rise in CS secretion that was blocked by the synthetic glucocorticoid dexamethasone. The mu-opiate antagonist beta-funaltrexamine blocked the morphine-induced rise in CS secretion, and the kappa-antagonist norbinaltorphimine blocked the action of U50,488H. While a maximal dose of U50,488H (1 mg/kg) elicited a significant rise in CS secretion as early as postnatal day 2, significant effects of a maximal dose of morphine (5 mg/kg) were not observed until day 5. The effects of both drugs were significantly blunted during the stress-hyporesponsive period from days 5-15. The results of this study demonstrate that significant opiate receptor control of HPA function can be demonstrated early in postnatal development, even before the onset of the stress-hyporesponsive period. In addition, these data suggest that kappa-receptor control is functional before mu-receptor control of HPA function.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1991

Control of expression of insulin resistance and hyperglycemia by different genetic factors in diabetic C57BL/6J mice.

The inheritance of the tendency to develop diet-induced non-insulin-dependent (type II) diabetes was analyzed in crosses between diabetes-prone C57BL/6J (BL/6) mice and diabetes-resistant A/J mice. The effects of a diabetogenic diet on blood glucose and insulin levels, insulin sensitivity, and weight were evaluated in F1 and both (BL/6 X A/J) F1 X BL/6 and (BL/6 X A/J) F1 X A/J backcross mice. These results suggest that diet-induced hyperglycemia is largely determined by a recessive gene and diet-induced insulin resistance by a dominant gene. Analyses of both backcrosses indicated that insulin sensitivity and blood glucose levels were unrelated, suggesting that they are controlled by different genetic factors. This conclusion was supported by data from nine recombinant inbred BXA strains in which no correlation was observed between these variables. Furthermore, insulin sensitivity and body weight correlated differently in the two backcross groups, suggesting that insulin resistance is not simply a function of obesity. The number of genes that predominantly influence diabetic traits was estimated by comparing the variance observed in (BL/6 X A/J) F1 X BL/6 backcross mice with that observed in parental mice. The data suggest that relatively few genes predominantly affect the diabetic phenotype in this murine model.

Animals↗

PubMed1991

Monoamine mediation of cocaine-induced hypothalamo-pituitary-adrenal activation.

The acute administration of cocaine (5-20 mg/kg) to rats produced a dose-dependent elevation in both serum corticosterone and plasma adrenocorticotrophic hormone (ACTH). These elevations were maximal at 30 min and returned to basal values by 60 min. The dopamine (DA) uptake blockers GBR12909 and nomifensine, the norepinephrine uptake blocker desipramine, as well as the serotonin (5-HT) uptake blocker fluoxetine, also stimulated hypothalamo-pituitary-adrenal (HPA) axis activity, whereas the local anesthetic procaine did not. Pretreatment with haloperidol (0.2 mg/kg) significantly attenuated the elevations in corticosterone and ACTH elicited by cocaine, as well as the elevation in ACTH produced by GBR12909. Higher doses of haloperidol (1 or 3 mg/kg) also attenuated the HPA response to cocaine and GBR12909. Pretreatment with the D1 antagonist SCH23390, the D2 antagonist sulpiride, the D1/D2 antagonist fluphenazine, or the 5-HT2 antagonist ketanserin significantly decreased the ACTH elevations after cocaine. In contrast, neither the 5-HT antagonist cyproheptadine, the alpha-1 antagonist prazosin nor the beta adrenergic antagonist propranolol attenuated the ACTH response to cocaine. The present results suggest an important stimulatory role for DA in regulation of HPA activity, and a role for both DA and 5-HT in the adrenocortical stimulation by cocaine. Both D1 and D2 receptors appear to be involved in the dopaminergic component of this response.

Adrenocorticotropic Hormone↗

PubMed1990

Aerobic exercise reduces levels of cardiovascular and sympathoadrenal responses to mental stress in subjects without prior evidence of myocardial ischemia.

Thirty-seven healthy type A men (mean age 42 years) were randomly assigned to either an aerobic exercise training group or to a strength and flexibility training group. Before exercise, subjects underwent comprehensive physiologic and behavioral assessments, including graded exercise treadmill testing with direct measurement of oxygen consumption (VO2) and measurement of cardiovascular (heart rate, systolic and diastolic blood pressure and rate pressure product) and neuroendocrine (epinephrine and norepinephrine) responses to mental arithmetic. The aerobic exercise consisted of walking and jogging at an intensity of greater than or equal to 70% maximal heart rate reserve for 1 hour 3 times/week for 12 consecutive weeks. The strength training consisted of 1 hour of circuit Nautilus training 2 times/week for 12 weeks. At the completion of the exercise program, all subjects underwent repeat testing. For the aerobic group, peak VO2 increased significantly from 33.6 to 38.4 ml/kg/min (p less than 0.001), whereas the strength group only achieved a slight increase from 34.5 to 35.6 ml/kg/min (difference not significant). During the mental arithmetic, the aerobic group experienced a greater reduction in levels of heart rate, diastolic blood pressure and rate pressure product than the strength group (after completing the exercise training programs). The aerobic group also tended to secrete less epinephrine and to show a faster recovery than the strength group after the exercise program. In addition, the aerobic group tended to exhibit less cardiovascular reactivity to mental stress after exercise training. These data suggest that aerobic exercise reduces levels of cardiovascular and sympathoadrenal responses during and after mental stress.

Adrenal Medulla↗

PubMed1990

Endocrine responses to mother-infant separation in developing rats.

Separation of neonatal rat pups from the dam have been reported to elicit two endocrine responses in the pup: a fall in growth hormone secretion and a rise in corticosterone secretion. However, the temporal, ontogenetic, and behavioral determinants of these responses have not been compared. In the present study, we report that these two responses can be differentiated on each of these criteria. Growth hormone secretion falls rapidly immediately upon separation of pups from the dam, while robust rises in corticosterone secretion are delayed for many hours. In addition, growth hormone responses are observed earlier in ontogeny. Finally, active maternal behavior is required for normal growth hormone secretion in 10-day-old rat pups, while passive sensory stimuli associated with the dam can significantly reduce the corticosterone response to separation.

Animals↗

PubMed1990

Evaluation of selective liver denervation methods.

This study compares four methods of hepatic denervation and defines the rate and physiological significance of reinnervation. Five groups of rats were prepared: 10 underwent orthotopic liver transplantation. In nine rats a 90% aqueous phenol solution was applied circumferentially to the portal vein. Thirteen rats underwent microsurgical denervation; 28 received different doses of 6-hydroxydopamine (6-HODA) administered as a single intraportal injection [50 (n = 10), 75 (n = 6), and 100 mg/kg (n = 6)]. Twelve rats were studied as controls. Rats were killed 1, 4, and 8 wk after surgery to determine liver tissue content of norepinephrine (NE). Changes in mean arterial pressure (MAP) in response to hepatic nerve stimulation, which was supramaximum in intensity and frequency, were measured before rats were killed. NE content in controls ranged from 121 to 204 ng/g and MAP increased by 30-38 mmHg after electrical stimulation. At 1, 4, and 8 wk after treatment the liver NE content was less than 1, 2.3, and 20.2 ng/g in the transplant group; less than 1, 2.7, 4.1 ng/g in the phenol group; and 17.2, less than 1, and 3 ng/g in the surgically denervated group. In the 6-HODA group, values were 18.9, 47, and 61.5 ng/g (50 mg/kg); 5.7, 20.2, and 15 ng/g (75 mg/kg); and 7.7, 2.5, and 17.5 ng/g (100 mg/kg). When the level of NE was undetectable, MAP increase after stimulation was 0-18% that of controls. When NE content was 15-23% of normal, MAP increased 49-62% regardless of the denervation technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effects of specific mu and kappa opiate tolerance and abstinence on hypothalamo-pituitary-adrenal axis secretion in the rat.

Chronic administration of opiates to rats results in HPA axis tolerance and abstinence-induced hypersecretion. The effects of specific mu and kappa tolerance and withdrawal on the functional secretion of the HPA axis were evaluated in this study. Adult male rats were injected s.c. twice daily with saline, morphine or U50,488 for 5 days. Serum adrenocorticotrophic hormone (ACTH) or corticosterone (CS) were determined by radioimmunoassay as measures of HPA axis function. Tolerance to morphine (10 mg/kg) and U50,488 (1 mg/kg), but no cross-tolerance, was observed suggesting the development of mu- or kappa-specific tolerance, respectively. Tolerance does not occur at the pituitary or adrenal levels after these paradigms because ACTH and CS responses to exogenous corticotropin-releasing factor and ACTH, respectively, were not attenuated. CS secretion in response to novelty stress was not affected by either chronic opiate treatment, but the circadian variation of CS levels was slightly blunted after chronic morphine. In contrast, the elevation of CS secretion by quipazine (0.5 mg/kg) and physostigmine (0.1 mg/kg) was attenuated after chronic U50,488, but not morphine administration. Both spontaneous and antagonist-precipitated withdrawal from morphine, but not U50,488, resulted in elevation of CS levels. Low doses of morphine suppressed morphine abstinence-induced CS hypersecretion, whereas, U50,488 and clonidine had no effect. In conclusion, alterations of HPA axis function occur during chronic mu or kappa opiate administration that are receptor-specific and involve multiple neural controls of the HPA axis.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Anterior and posterior, but not cheek, intraoral cannulation procedures elevate serum corticosterone levels in neonatal rat pups.

Implantation of intraoral cannulas is a procedure that has been typically assumed to be relatively unstressful in neonatal rat pups. To test this assumption, endocrine responses to such implantations were compared with those of other standard procedures. In Experiment 1, corticosterone and growth hormone (GH) levels were assessed in 4-day-old rat pups placed in an incubator for 15 or 60 min following either: no treatment, subcutaneous (sc) injection of 0.9% NaCl, anterior or posterior intraoral cannulation, ice anesthesia or ether anesthesia. Corticosterone levels were elevated relative to nontreated controls 15 min after all treatments except sc injection. These levels remained elevated after 60 min in both cannulation groups and the ice anesthesia group. In Experiment 2, the ability of ether anesthesia to reduce the hormonal response to the cannulation procedures was assessed in addition to examining the hormonal response to intraoral cannulations through the cheek in 4-day-old rat pups. Ether did not attenuate the corticosterone response to either anterior or posterior cannulations. Pups subjected to the cheek cannulation procedure did not exhibit any significant alterations in serum corticosterone levels when compared with nontreated control pups. GH levels were found to differentiate less among the various procedures than corticosterone levels, with GH levels generally being low in all groups, including nontreated control animals. These data suggest that a cheek placement is less stressful than anterior and posterior placements and may provide a viable alternative in studies necessitating the implantation of cannula into the buccal cavity during the early postnatal period.

Anesthesia, General↗

PubMed1989

Abnormalities in the response of plasma arginine vasopressin during hypertonic saline infusion in patients with eating disorders.

We examined the response of plasma arginine vasopressin (pAVP) to intravenous 5% hypertonic saline in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Patients did not differ from controls in their subjective response for the onset of thirst; however, only 5 patients (3 AN and 2 BN) showed pAVP levels that were within the normal range (0.5-11.0 pg/ml) for this test. With the exception of two eating disorder (ED) patients, all others showed some nonlinear irregularities in the pattern of their secretion of pAVP in response to the hypertonic saline infusion. Seven of the ED patients showed an irregular abnormally high pAVP secretion, and three patients showed abnormally low pAVP responses. Both of these pAVP secretion abnormalities occurred in underweight and weight-recovered AN patients, as well as in BN patients. The cause and pathophysiological consequences of these abnormalities remain unresolved.

Adolescent↗

PubMed1989

Delayed suppression of serum luteinizing hormone after naloxone treatment in neonatal female rats.

In female neonatal rats, opiate receptor blockade markedly raises serum luteinizing hormone (LH) levels. The LH effect of acute treatment with opiate antagonists is apparently brief in older rats; however, age-related differences in antagonist pharmacokinetics may result in different LH response patterns. The duration of LH response to naloxone (NAL) and naltrexone (NTX) was examined in 5 day-old (d.o.) female rats and compared to the duration of analgesia blockade. The rise in serum LH following opiate receptor blockade in 5 d.o. rats was of similar duration to that previously observed in older animals and much briefer than blockade of analgesia. Furthermore, neonatal rats exhibited a delayed suppression of LH 6 hr following NAL, but not NTX, treatment. Stimulation and later suppression of LH were still observed after five repetitive NAL treatments at 6 hr intervals.

Animals↗

PubMed1989

Differential glycemic effects of morphine in diabetic and normal mice.

C57BL/6J ob/ob mice, C57BL/6J+/? lean mice and A/J mice were given injections of 10 mg/kg of morphine or an equal volume of saline, and then blood was sampled by retroorbital sinus puncture. In addition, animals from each strain were exposed to a brief experimental stress ten minutes after the administration of morphine or saline. While morphine produced significant increases in serum glucose in albino mice, morphine lowered blood insulin in both C57BL/6J ob/ob and C57BL/6J+/? mice. Morphine significantly lowered blood insulin in A/J mice, but effects in C57BL/6J mice were not significant. In contrast, morphine attenuated blood glucose and insulin during stress in C57BL/6J ob/ob but did not significantly affect either glucose or insulin during stress in lean C57BL/6J or A/J mice. These results are interpreted in the light of other data suggesting that endogenous opiates modulate the effects of sympathetic nervous system activity in type II diabetes.

Animals↗