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Biomedical subjects

M Weinstock

Publications and source records attributed to M Weinstock.

At least 55 records · Page 3Linked to original sources
PubMed1995

Maternal naltrexone prevents morphological and behavioral alterations induced in rats by prenatal stress.

The influence of opioid receptor blockade on the developmental and behavioral effects of prenatal stress was studied. Time-mated dams were implanted with minipumps on day 17 of gestation containing vehicle (V) or naltrexone (NTX, 10 mg/kg/day). Noise and light stress was applied on an unpredictable basis, three times a week throughout gestation to half the dams. Maternal NTX completely prevented the reduction in anogenital distance in prenatally stressed (PS) males and restored the growth rate of both sexes. NTX also decreased the anxiety of PS rats in the plus-maze, increased the opioid component of exploration to control levels, but increased anxiety in control males. NTX did not restore the lower saccharin preference in PS females and decreased it in C females. This suggests that some morphological and behavioral changes induced by prenatal stress could result from excess opioid activity induced by maternal stress.

Animals↗
PubMed1995

Comparison of the effects of angiotensin II, losartan, and enalapril on baroreflex control of heart rate in conscious rabbits.

We compared the effects of angiotensin II (AII), enalapril, and losartan given by acute intravenous (i.v.) injection, on cardiac baroreflex sensitivity in two groups of conscious normotensive rabbits bred for high gain [> 5 beats/min/mm Hg] (group I) and low gain [< 4 beats/min/mm Hg] (group II) of the mean arterial blood pressure-heart rate (MAP/HR) relationship, respectively. Full sigmoid barocurves were produced in 62 rabbits by i.v. injection of phenylephrine (PE 1-15 micrograms/kg) and nitroglycerin (NTG 1-20 micrograms/kg) after pretreatment with saline or with AII, enalapril, or losartan. In group II, AII had a biphasic effect on baroreflex sensitivity; at 10 and 50 ng/kg/min, it increased the gain from 3.47 +/- 0.21 to 4.75 +/- 0.44 and 5.13 +/- 0.28 beats/min/mm Hg (p < 0.05 and p < 0.025, respectively), but had no effect at 100 ng/kg/min. BP increased in these rabbits by 11.5, 10, and 23 mm Hg after these three doses. In group I, AII 50 ng/kg/min increased BP by 8 mm Hg, (p < 0.05) and decreased gain from 6.13 +/- 0.32 to 4.75 +/- 0.44 beats/min/mm Hg (p < 0.01). Therefore, AII 50 ng/kg/min equalized baroreflex sensitivity in the two groups. In group II, both losartan (2.5 mg/kg) and enalapril (1 mg/kg) decreased BP by 8.6 +/- 1.0 1.0 and 10.2 +/- 2.1 mm Hg, (p < 0.01), respectively, and increased the gain by 1-2 beats/min/mm Hg; the drugs did not influence baroreflex sensitivity to any significant extent in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Cardiac baroreflex sensitivity and sodium excretion are reduced both by a deficit and an excess of dietary salt in the conscious dog.

In 10 conscious, chronically instrumented beagle dogs we studied the effects of four different dietary sodium intakes (mmol Na/kg body wt/day: 14.5 [excess], 7.5 [high], 2.5 [normal], and 0.5 [low] [plus an additional standardized sodium depletion produced by peritoneal dialysis several days before the experiments]) on cardiac baroreflex sensitivity and renal response to an acute saline load. Full sigmoid barocurves were produced by intravenous injection of phenylephrine (2.5 to 20 micrograms/kg) and nitroglycerine (2.5 to 30 micrograms/kg). The gain of this relationship was significantly decreased by both an excess and low sodium intake (8.0 +/- 1.0 and 8.3 +/- 0.8 beats/min/mm Hg, respectively) when compared with the 2.5 and 7.5 (12.1 +/- 1.4 and 16.0 +/- 1.7 beats/min/mm Hg, respectively) mmol Na/kg/day sodium intake. Water and sodium excretion in response to saline infusion were lower in the 0.5 and 14.5 mmol/kg/day sodium intake groups in spite of the higher atrial natriuretic peptide and lower plasma renin activity and plasma aldosterone levels in the latter. Mean arterial blood pressure, heart rate, and central venous pressure increased during saline loading in all groups; hematocrit and plasma protein concentration decreased similarly in all groups. The results suggest that the rapid renal homeostatic response to an acute salt load in animals kept chronically on normal or moderately increased dietary sodium intake is regulated by baroreflex control of the renal homeostatic response. Excess dietary sodium intake attenuates baroreflex sensitivity and delays sodium and water excretion after acute loading.

Animals↗
PubMed1994

Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors.

The pharmacological and clinical properties of a novel phenyl carbamate acetylcholinesterase (AChE) inhibitor, SDZ ENA 713 are described. In animals and human subjects this compound showed superior chemical stability, oral bioavailability and a longer duration of action than physostigmine. SDZ ENA 713 produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than in the heart and skeletal muscle, which explains its relatively low toxicity and freedom from cholinergic side effects. The selective effect in the cortex and hippocampus may be due to its preferential inhibition of the G1 form of the enzyme, which is present in relatively higher concentrations in these brain areas. Evidence of a selective hippocampal action was obtained in normal human subjects in whom REM sleep density was increased at doses that had no effect on plasma cholinesterase. If memory impairments in AD are related to a lack of cholinergic activity in cortical and hippocampal brain areas, SDZ ENA 713 should produce significant symptomatic improvement.

Animals↗
PubMed1993

Rabbits with a genetic impairment in baroreceptor reflex sensitivity show abnormal renal haemodynamics and proximal tubular sodium reabsorption in response to a saline infusion.

OBJECTIVE: To compare renal haemodynamics and proximal tubular sodium reabsorption (PTSR) in response to an acute intravenous saline infusion in rabbits bred for genetic differences in cardiac baroreflex sensitivity (BRS). Rabbits with low BRS increase their blood pressure significantly on a high-salt diet, in association with an initial delay in sodium excretion. It was hypothesized that this could occur through an impaired baroreflex regulation of renal sympathetic nerve activity. This, in turn, would alter renal blood flow and PTSR. DESIGN: Experiments were performed in two groups of normotensive male rabbits (n = 10 per group), one of which had high BRS (> 5 beats/min per mmHg; group I) and one of which had low BRS (< 4 beats/min per mmHg; group II). Effective renal plasma flow (ERPF) was measured by para-aminohippuric acid clearance, and PTSR by the lithium clearance technique. Sodium, lithium, para-aminohippuric acid and glomerular filtration rate were measured from urine samples collected every 30 min (for 90 min) via an indwelling bladder catheter, during a control infusion of glucose (30 mg/ml) NaCl (1.8 mg/ml), and for 2 h after a threefold increase in NaCl. RESULTS: Group I rabbits increased their ERPF by approximately 40%, in response to saline, and doubled their sodium and lithium clearances within the 2 h, but those in group II did not change their cation excretion or their ERPF significantly during this period. Blood pressure did not increase in either group. CONCLUSIONS: A genetic impairment in BRS may be responsible for the inadequate depression of renal sympathetic nerve activity, which results in a failure to increase ERPF and suppress sodium reabsorption in the proximal tubule in response to salt loading.

Absorption↗
PubMed1993

Low baroreflex sensitivity predisposes to salt-sensitive hypertension in the rabbit.

The aim of this study was to determine the effect of an increase in dietary salt on blood pressure (BP), Na+ balance, and plasma renin activity (PRA) in normotensive rabbits bred for differences in cardiac baroreflex sensitivity (BRS). Food and fluid intake, BP, heart rate, body weight, PRA, hematocrit, and creatinine clearance were monitored weekly and Na+ balance daily for 3 wk each on normal NaCl (8 meq/day) and high salt (32 meq/day) in 27 rabbits of the second and third generation of animals bred for high BRS (group I, 6.1 +/- 0.3 beats.min-1.mmHg-1, n = 9) or low BRS (group II, 3.61 +/- 0.1 beats.min-1.mmHg-1, n = 18). BRS was assessed in each animal on normal salt and at the end of the high-salt period. Both systolic and diastolic BP rose by > 10 mmHg in 50% of group II and by < 5 mmHg in the remainder and in all group I. The rise in BP was associated with Na+ and fluid retention and weight gain during the first 2 wk, which returned to presalt levels by the 3rd wk, although BP continued to rise. The lack of effect on BP in the remaining nine group II was associated with a marked sensitization of their BRS by the high salt to 6 +/- 0.4 beats.min-1.mmHg-1. BRS remained unchanged in the other rabbits. A highly significant correlation (P < 0.001) was found between the increment of BP and BRS after 3 wk of raised salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat.

A study was made of the effects of prenatal stress on the reactivity of the hypothalamic-pituitary adrenal (HPA) axis in male and female offspring. Rat dams were subjected to noise and light stress on an unpredictable basis throughout pregnancy. At 28 days of age mRNA for POMC, proenkephalin and prodynorphin were measured in the hypothalamus of the offspring. A marked reduction was found in POMC mRNA in PS females (PSF) but not in males (PSM), but the other mRNA's did not differ from controls (C). At 60 days of age, PSF has 3 times higher resting levels of serum corticosterone (COR) and significantly lower dexamethasone (DEX)3H hippocampal binding sites than CF. Overnight adrenalectomy abolished the difference in DEX binding. After 10 min exposure to open field PS males and females voided more fecal pellets and made fewer center entries than C offspring, testifying to increased emotionality. Open field stress caused a 3-5-fold rise in circulating COR in all groups within 15 min, which returned to baseline by 90 min in all rats except PSF. These data show that prenatal stress can cause permanent alterations in the behavior of both sexes in stressful situations but appears to cause a selective effect on the HPA axis in the female rat.

Animals↗
PubMed1992

Contrasting influences of central and peripheral opioids on cardiac baroreflex sensitivity in rabbits.

We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 micrograms/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 micrograms/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 micrograms/kg) and nitroglycerin (1-20 micrograms/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antagonism of morphine-induced respiratory depression by novel anticholinesterase agents.

This study compared the effects of 3 novel antiAChE agents (derivatives of dimethylaminoethyl-phenyl carbamate) with that of physostigmine on the respiratory depression induced by morphine in rabbits. Each drug, RA6, (1 mg i.v., 2 mg s.c.) RA7 (1 or 2 mg i.v.); RA15 (0.25 or 0.5 mg i.v.), physostigmine (0.05 or 0.1 mg i.v.) or saline (1 ml), was injected simultaneously with morphine (8 mg i.v.) to groups of 6-10 rabbits. Respiration rate, blood gases and pH were monitored for 3 hr. Plasma ChE was measured before and at 15 min intervals after injection. The 4 antiAChE's were given to 40 other rabbits, which were sacrificed at the time of maximal antagonism of the respiratory depressant effect of morphine, in order to measure the activity of AChE in the medulla, cortex and hippocampus. Physostigmine (0.1 mg) only antagonized the increase in paCO2 induced by morphine at 15 and 30 min. The drugs RA15 (0.5 mg), RA6 (2.5 mg) and RA7 (2 mg) almost completely prevented the respiratory depression, without obvious signs of peripheral cholinergic hyperactivity, for at least 3 hr. There was no relationship between the degree of antagonism of the effects of morphine with any drug and that of inhibition of ChE in plasma. In contrast, a highly significant correlation (P less than 0.01) was found between the former and the amount of inhibition of AChE in the medulla. It is suggested that the novel carbamates may have potential therapeutic application in reducing the respiratory depression of opiates, without impairing analgesia.

Acetylcholinesterase↗
PubMed1991

Relationship between baroreflex sensitivity, renin suppression and natriuresis in salt-sensitive rabbits.

This study determined the influence of baroreflex sensitivity (BRS) on the rate of urinary sodium excretion and plasma renin activity (PRA) in response to a saline infusion in conscious male rabbits specifically bred for high (Group I; n = 7) and low (Group II; n = 10) BRS and in seven control animals. Only Group II showed significant increases in blood pressure on a chronic high-salt intake. After ensuring that each animal was in sodium balance, a (0.7-0.9%) saline infusion of 3-4 ml/kg per h for 90 min (25% daily sodium intake for each rabbit) was given and urine collected at 15-min intervals via a bladder catheter. No differences were found in control urine volumes, urinary sodium or PRA. Group I excreted over 50% of the sodium load and Group II less than 20% within 90 min. PRA fell by more than 30% within 30 min in six Group I rabbits but decreased by less than 30% or increased in Group II. In the control animals, sodium excretion rates and PRA suppression were also much greater in those with high BRS. A highly significant correlation (r = 0.808, P less than 0.01) was found between the per cent of the sodium load excreted and BRS. It is suggested that the delayed sodium excretion and blood pressure elevation in salt-sensitive subjects may be due to a genetic impairment in baroreflex control of renal sympathetic nerve activity.

Animals↗
PubMed1990

Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress.

The aim of this study was to see whether neonatal handling can reverse the behavioral deficits induced in rats by unpredictable prenatal stress. Rats (24) were exposed to random noise and light stress (RS) on a random basis throughout pregnancy. Half the litters of RS and control (C) dams were subjected to neonatal handling (NH), 3' daily for 21 days. Behavioral measures, open field in both sexes and plus maze test in females only were conducted at 1.5-2 months, and spatial lateralization by amphetamine-induced rotation, in females at 3 months. RS caused significant increases in emotionality and timidity (higher incidence of defecation and less time in open arms of plus maze), and a change in directional bias towards the left. NH completely reversed all these behavioral abnormalities in RS rats but had little effect in C. It is concluded that NH can influence postnatal development of brain organisation in the opposite direction to that induced by prenatal stress.

Animals↗
PubMed1989

Alterations in behavioral and striatal dopamine asymmetries induced by prenatal stress.

We investigated the effects of maternal noise and light stress, randomly applied throughout pregnancy, on the development of behavioral and neurochemical asymmetries in the rat offspring. This form of maternal stress resulted in a rightward positioning of the tail of both sexes soon after birth as opposed to the leftward bias in controls. At adulthood, prenatally stressed offspring showed a change in directional bias compared to controls with a preponderance of left turns after amphetamine. In the males, this was expressed as a reduction in directional preference, while in females a reversal occurred of their dominant turning direction from right (controls) to left. We also observed a reduction in dopamine turnover rates in the left corpora striata of stressed offspring of both sexes. Again, in the females, this change was particularly marked and resulted in a reversal towards the right hemisphere. The findings from this study are consistent with the possibility that the alterations in cerebral asymmetries induced by prenatal stress may underly the decrease in the ability of the offspring to cope with anxiety provoking situations.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Opioid peptides mediate sympathetic inhibition in response to baroreceptor activation in a distinct genetic strain of rabbit.

1. Two strains of rabbits have been bred with marked differences in their cardiac baroreflex sensitivity (BRS). The difference in cardiac BRS was attenuated by naloxone. We compared the sympathetic responses to a pressor stimulus in these two strains, by measuring the changes in plasma catecholamines in the presence and absence of naloxone. 2. Cardiac BRS was assessed in eight rabbits of each group by the steady-state method. Two weeks later, both ear arteries and one ear vein were cannulated. Mean arterial pressure (MAP) and heart rate (HR) were recorded from one artery and blood samples (5 mL) for plasma catecholamines (CA) taken before, and during the peak of the pressor response to intravenous phenylephrine (PE, 20 micrograms/kg) from the other. The experiment was repeated 2-3 weeks later in rabbits with high BRS (Group I) after injection of naloxone 0.1 mg/kg, i.v. 3. Resting MAP and HR did not differ in the two groups. The mean gains of the cardiac baroreflex were 23.3 +/- 2.2 ms/mmHg in Group I and 6.3 +/- 1.1 ms/mmHg in Group II. After PE, MAP rose by 54.5 +/- 1.8 mmHg in Group II and 40.3 +/- 3.6 mmHg in Group I (P less than 0.02). The pressor response was associated with a 31% reduction in plasma noradrenaline (NA) in Group I and a 34% increase in Group II. The reduction in NA was significantly correlated with the degree of bradycardia in Group I (r = 0.72, P less than 0.05) and with BRS in both groups (r = 0.78, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prenatal stress increases anxiety related behavior and alters cerebral lateralization of dopamine activity.

Effects of unpredictable (random) prenatal stress on the level of anxiety and cerebral lateralization of dopamine turnover rates were studied in rats. The observation of a decrease in the amount of time spent in the open arms of a "plus-maze" supported earlier findings of an increased fearfulness to stressful situations in the offspring in adulthood. We also observed elevated rates of dopamine turnover in the right prefrontal cortex and reduced dopamine activity in the right nucleus accumbens and left corpus striatum of the prenatally stressed animals. This resulted in directional shifts of left-right differences in dopamine activity in all 3 areas. These findings indicate that prenatal stress induces permanent alterations in dopaminergic activity and in cerebral asymmetry. We suggest that the changes in cerebral lateralization of dopamine function may underly the increase in reactivity to anxiety-provoking situations in prenatally stressed offspring.

Animals↗
PubMed1988

Differentiation of cardiac baroreflex properties by cuff and drug methods in two rabbit strains.

Sigmoidal mean arterial pressure (MAP)-heart rate (HR) curves were obtained in two genetically related strains of rabbits (groups I and II). We examined vagal (V) and sympathetic (S) effects on HR using perivascular cuffs and vasoactive drugs to alter MAP, and we studied the effects of intravenous naloxone, which affected only I. With the cuff method, both V and S components of gain were much greater in I than in II, and naloxone greatly reduced the difference. With the drug method, gain was similar in I and II and unaffected by naloxone. With both methods, the V component of HR range between plateaus was greater in I than in II because of more pronounced bradycardia at the lower plateau; naloxone eliminated the latter difference when the reflex was drug induced but not when it was cuff induced. The S component of HR range was similar in I and II; with both methods, the tachycardia plateau was reduced by naloxone. The cuff method alters cardiac load more than the drug method, leading to engagement of different groups of afferents for a given change in MAP (delta MAP). We have derived an input-output model, which suggests that with the drug method, gain is almost entirely determined by the input from the arterial baroreceptors, accounting for the minimal difference between I and II. With the cuff method, gain is determined by a nonlinear interaction involving the arterial and nonarterial baroreceptors, which accentuates the response. The opiate mechanism is associated with the nonarterial baroreceptor input and has amplifying properties, which account for the difference in gain between I and II. The two methods and naloxone provide a novel way of differentiating the effector patterns of the reflex; naloxone serves as a marker of activity in a particular pathway.

Animals↗
PubMed1988

[Hereditary resistance to salt-induced hypertension. What mechanisms?].

The Sabra hypertension resistant rats (SBN) have an outstanding ability to maintain normal blood pressure when exposed to procedures that ordinarily cause hypertension in normal rats. The following findings may be relevant to resistance to hypertension of these rats: 1) In SBN rats, cardiac norepinephrine content is not affected by DOCA-salt treatment. Since depletion of cardiac norepinephrine is an index of cardiac adrenergic nerve overactivity, the results suggest an attenuated cardiac sympathetic nerve activity in these rats. 2) In SBN rats, the sensitivity of the baroreflex control of the heart is markedly increased compared with other strains. Reduction of baro-receptor sensitivity by aortic-baroreceptor deafferentation renders them susceptible to DOCA-salt hypertension. The results suggest a strong relationship between baroreflex supersensitivity and resistance to hypertension in these rats. 3) The amount of alpha 2 adrenoreceptor densities in cerebral and renal cortical membranes of normal rats increased in vitro, in the presence of sodium and guanyl nucleotide (GTP). In SBN rats, the effect of sodium is markedly attenuated compared with SBH, while response to GTP is identical in the two strains. The demonstration of a similar pattern of response in the Dahl rats suggests that alpha 2 adrenoreceptor may be involved in the sensitivity or resistance to salt induced hypertension.

Animals↗
PubMed1987

Increased interhemispheric coupling of the dopamine systems induced by prenatal stress.

Maternal noise and light stress, randomly applied throughout pregnancy, has previously been shown to induce alterations in behavioral asymmetries in the adult offspring. In the present study, we investigated whether interhemispheric communication of neurotransmitters would be influenced by this treatment. Dopamine and serotonin turnover rates were measured in the left and right prefrontal cortex, nucleus accumbens and caudate nucleus of adult rats which were stressed prenatally. In control animals, dopamine turnover was only significantly correlated between the left and right hemispheres in the males (p less than 0.01). Prenatal stress greatly increased the degree of interhemispheric correlation (p less than 0.001) which now became highly significant in both sexes (p less than 0.001). For serotonin, left-right turnover rates only correlated in control females and no effect of gestational stress was seen. These results indicate that prenatal stress greatly increases interhemispheric coupling of dopamine in the adult offspring. We suggest that this facilitated communication may underly the alterations in behavioral asymmetries induced by prenatal stress.

3,4-Dihydroxyphenylacetic Acid↗