Search PubMed⌕ Search

Biomedical subjects

D A Blizard

Publications and source records attributed to D A Blizard.

At least 37 records · Page 2Linked to original sources
PubMed1991

Ethanol preference in the Harrington derivation of the Maudsley Reactive and Non-Reactive strains.

Ethanol intake was explored in the Harrington derivation of the Maudsley Reactive and Maudsley Non-Reactive rat strains (MR/Har and MNRA/Har). When 5% and 10% ethanol solutions were presented as the sole source of fluid (1-bottle test), MR/Har rats, respectively, ingested 15% more, or 9% less, than their baseline water intake, whereas MNRAs ingested 6% less, or 42% less than their baseline intake. However, because MNRA/Har rats drank significantly more water than MR/Har's under ad libitum conditions (MNRA/Har, 46.6 +/- 1.83 ml; MR/Har 32.45 +/- 1.64 ml/24 hr), males and females of the two strains ingested a similar amount of ethanol in the 1-bottle test (5% ethanol, 4-7; 10% ethanol, 6-12 g/kg body weight/24 hr). In 2-bottle free-choice tests administered after an extended period of forced ethanol consumption, MR/Har male and female rats exhibited a strong ethanol preference (X = 80%) and consumed a larger amount of ethanol (MR/Har, 7-13; MNRA/Har, 6-9 g/kg body weight/24 hr) than MNRA/Har's. Across all conditions, females of both strains ingested a greater relative amount of ethanol than males. The strain difference in ethanol preference was found to be independent of prior exposure to ethanol because it was also found when 2-bottle free-choice tests were carried out in naive animals (Experiment 2). The pattern of development of ethanol preference in individual animals was characterized by abrupt onset, after variable periods of exposure to the 2-bottle choice test, and maintenance of strong ethanol preference thereafter. The extensive behavioral and biological definition of the Maudsley strains is a valuable asset in attempting to elucidate the biobehavioral correlates of ethanol preference.

Alcohol Drinking↗
PubMed1991

The effect of a high salt diet and gender on blood pressure, urinary protein excretion and renal pathology in SHR rats.

A high salt diet produced increases in SBP, urinary protein excretion (UPE) and renal vascular lesions (RVL) across groups of male and female SHR rats which were allowed to develop moderate or excessive increases in SBP. A highly significant linear relationship between SBP and log-transformed UPE was found when the data from all groups were analyzed together. Males developed high blood-pressure more rapidly, and exhibited more severe RVL and greater UPE than females. Two results prevent the conclusion that the elevated UPE was simply due to the adverse effects of high BP on the kidney. First, the relationship between SBP and UPE across groups could not be demonstrated when regression analyses were performed within individual dietary sub-groups. Secondly, gender differences in UPE were highly significant by analysis of covariance adjusting for individual differences in SBP. The increases in SBP and UPE may be independent consequences of ingestion of a high salt diet.

Animals↗
PubMed1991

Dietary salt and accelerated hypertension: lack of sub-line differentiation in spontaneously hypertensive rat stocks from the United States.

We compared the ability of a high-NaCl diet to produce blood pressure elevation in spontaneously hypertensive rats (SHR) from the major North American commercial suppliers (Harlan, Taconic Farms, Charles River) and SHR and stroke-prone SHR (SHRSP) from the National Institutes of Health (NIH). Animals were raised on a low-NaCl diet containing 0.30% NaCl and placed on an 8.0% NaCl diet at 37 days of age. In males, the high-NaCl diet produced large increments in blood pressure within 2-4 weeks, which were similar in magnitude for all SHR derivations. In females, increments in blood pressure occurred more slowly than in males but, in most SHR derivations, the absolute blood pressure level eventually reached was similar to that seen in males. The present findings provide no evidence of sub-line differentiation among SHR stocks from the United States regarding the blood pressure-augmenting effects of increased levels of NaCl and are consistent with the results of DNA fingerprinting studies, which have not found any genetic variation between SHR from different colonies. We speculate that the pervasive gender differences in the blood pressure response to the high-NaCl diet in SHR may reflect gender differences in food intake, and hence the dose of NaCl received, rather than intrinsic differences between males and females. On the other hand, the lack of significant gender differences in blood pressure response to the high-NaCl diet in SHRSP may reflect the genetic differences which are known to exist between this strain and the main SHR stemline.

Animals↗
PubMed1990

Resource sharing in rat gestation: role of maternal cardiovascular hemodynamics.

There is a substantial decrease in blood pressure (BP) in late pregnancy in the laboratory rat. It is so pronounced that manipulations that produce sustained elevations in BP in nonpregnant animals have little or no effect during pregnancy. It is commonly believed that this decrease in BP is a consequence of a large decrease in total peripheral resistance resulting from the passive combination of the placental vasculature with a preexisting maternal vasodilation. An alternative view is presented here. We suggest that, in small mammals like the laboratory rat, pregnancy severely challenges the ability of the maternal cardiovascular system to meet its metabolic demands, so that during the last stages of maturation of the low-resistance placental circulation delivery of vital metabolic or nutritional substances to the maternal vasculature becomes marginal. When the so-called maternal hemodynamic preservation threshold is reached, a pronounced and wide-spread vasodilation occurs to maintain adequate perfusion of maternal organs. The late-gestational decrease in BP thus reflects a dynamic interaction between the maternal and placental circulations rather than reflecting their passive combination. The hypothesis provides a framework for the integrated discussion of a number of important phenomena: the fact that hypertensive rats exhibit a larger decrease in BP in late gestation than normotensive rats; the existence of a positive association between litter size and the magnitude of the late-gestational decrease in BP; and, finally, the well-established ability of the food-restricted pregnant rat to compartmentalize its nutritional resources.

Animals↗
PubMed1990

Modification of stroke susceptibility by genotype-dependent maternal influences.

The influence of the prenatal and postnatal maternal environment on stroke susceptibility was evaluated by reciprocally crossing the spontaneously hypertensive (SHR) and the Dahl salt-sensitive (SS/Jr) inbred rat strains to produce reciprocal F1 hybrids that were nurtured, respectively, during prenatal and postnatal life by SHR or SS/Jr mothers. Following placement on a high-salt diet containing 8% NaCl at 35 days of age, F1 rats reared by SHR mothers had shorter survival times and were more likely to die with cerebral hemorrhage than F1s reared by SS/Jrs. Across reciprocal F1 female groups, enhanced susceptibility to stroke was associated with greater elevations of systolic blood pressure, but this association was not seen across reciprocal F1 male groups. There was also an association between blood pressure and stroke within each F1/gender subgroup: Rats eventually suffering strokes developed higher blood pressure after placement on the high-salt diet than rats that did not suffer stroke. Lower day 35 body weights (before exposure to the high-salt diet) were associated with greater likelihood of stroke both across the reciprocal F1 groups, and within three of the four F1/gender subgroups. The differences in stroke susceptibility between the reciprocal F1 groupings may be due to systematic differences in the prenatal and/or postnatal environments of SHR and SS/Jr mothers and may be mediated by variations in the nutritive capacity of the two inbred mothers.

Animals↗
PubMed1990

Microtransferrinuria and microalbuminuria. II. In the rat.

We studied albumin and transferrin excretion in the normal and diabetic rat: (1) The rat secretes small concentrations of albumin and transferrin in the urine. (2) The secretion depends on the strain and was highest in the Kyoto spontaneously hypertensive rat. (3) The secretion of these two proteins in the rat is quite dependent on age and sex. The level increases dramatically with age. The secretion is much higher in the male compared to the female. This difference is observed after puberty. The changes in transferrin relative to those in albumin are much higher. (4) In streptozotocin-induced diabetes, the concentration of albumin and transferrin expressed as milligrams per liter decreases; however, the output/24 h or per gram creatinine is increased with a greater increase in transferrin output relative to that of albumin. The similarities and differences between excretion of these two proteins in the human and the rat as well as their importance are discussed.

Aging↗
PubMed1988

The locus ceruleus: a possible neural focus for genetic differences in emotionality.

The Maudsley Reactive and Non-Reactive strains have been developed as a model for the study of individual variations in stress-reactivity, and many differences in biobehavioral systems have been found between them. This review discusses limitations of the 'emotionality' construct in accounting for differences between the Maudsley strains and offers an alternative, theoretical approach. Amaral and Sinnamon have proposed that the locus ceruleus (LC) plays a stress-attenuating role in mediating behavioral, physiological and neuroendocrine response to prepotent, emergency-provoking stimuli and, building upon this formulation, it is proposed that the LC has been an important focus for gene action in the Maudsley model. It is suggested that the LC of the Non-Reactive strain is more strongly activated by stressful stimuli than the LC of Reactive rats, and is the basis of many of the behavioral and physiological differences between them. Behavioral and biochemical evidence consistent with this proposition is reviewed. Identification of the LC as a target for gene-action in the Maudsley model has an important advantage. It substitutes variations at a specific anatomic location in the brain for a loosely defined construct like emotionality, and the hypothesis is amenable to empirical tests by a variety of experimental approaches.

Animals↗
PubMed1988

Genetic influences on agonist binding to cardiac beta-receptors.

Regulation of beta-adrenoceptor-agonist function in the Maudsley Reactive (MR/Har) and the Maudsley Non-Reactive (MNRA/Har) rat strains was assessed by comparison of isoproterenol competition for [125I]iodocyanopindolol (ICYP) binding sites in crude left ventricular homogenate preparations. Non-linear, least-squares analysis of isoproterenol competition for ICYP binding in the absence of guanine nucleotide revealed different proportions of high- and low-affinity receptors in the two strains; MR/Har rats (59 +/- 3.3%) had a significantly greater proportion of receptors in the high-affinity state than the MNRA/Har rats (41 +/- 4.5%). Addition of the non-hydrolyzable guanine nucleotide analog guanylylimidodiphosphate (Gpp(NH)p) converted receptors to the low-affinity state. Analysis of Gpp(NH)p concentration-response curves in left ventricular homogenates of the two strains revealed that the MR/Har strain had a significantly (P less than 0.02) lower EC50 for guanyl nucleotide inhibition of isoproterenol competition for ICYP binding than the MNRA/Har. Confirming previous experimental results, a significantly (P less than 0.04) greater density of ventricular beta-receptors was found in MR/Har rats (13.16 +/- 0.92 fmol/mg protein) than in MNRA/Har rats (10.81 +/- 0.63 fmol/mg protein). Left ventricular catecholamine levels were found to be correlated inversely with beta-adrenoceptor density in the two strains; norepinephrine (NE) and epinephrine (EPI) concentrations (ng/mg protein) in left ventricle were 12.19 +/- 0.94 for NE and 0.165 +/- 0.038 for EPI in MNRA/Har, and 8.73 +/- 0.95 and 0.018 +/- 0.018, respectively, in MR/Har. All other parameters of agonist interactions with the cardiac beta-adrenoceptor for the MR/Har and MNRA/Har rat strains were similar [the IC50 for displacement of ICYP binding by isoproterenol, the accompanying Hill coefficients in the Gpp(NH)p present and absent condition, the Kd of the high- and low-affinity states in the absence of Gpp(NH)p, and the Kd of the uniform low-affinity state in the presence of Gpp(NH)p]. We hypothesize that the strain-dependent differences in high-affinity state formation reported here may account for some of the in vivo differences in cardiovascular function previously demonstrated in the Maudsley rats.

Adrenergic beta-Agonists↗
PubMed1988

Effects of stress and chronic propranolol infusion on cardiac beta-receptor function in the Maudsley Reactive and Non-Reactive rat strains.

The effects of beta-adrenoceptor blockade on left ventricular beta-receptor characteristics were evaluated in the Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rat strains. After propranolol infusion for one week administered by subcutaneously implanted osmotic minipumps, differences in beta-adrenoceptor-agonist interactions between strains were assessed by comparison of isoproterenol competition for [125I]iodocyanopindolol (ICYP) binding sites in crude left ventricular homogenate preparations from both strains. Propranolol exposure had no significant effect on the binding parameters investigated (Bmax, Kd, % receptors in high affinity state, IC50). In contrast to previous observations in naive animals, these experiments revealed no strain differences in the sham-implanted Maudsleys in any of the left ventricular beta-adrenoceptor parameters investigated. We hypothesize that the surgical procedures and/or presence of the plastic inserts acted as stressors in the Maudsley strains and thus altered beta-adrenoceptor function. This hypothesis is supported by the observation that exposure to another stress (footshock) also eliminated strain differences in ventricular beta-receptor binding variables.

Animals↗
PubMed1987

Contrasting effects of social stress and foot-shock on acute cardiovascular response in salt-sensitive rats.

Repeated defeat by an aggressive resident attacker rat produces a large decrement in systolic blood pressure (SBP) in male S/JR rats. The present experiments compared the cardiovascular (CV) response of male S/JR rats exposed either to repeated defeat, or to a common laboratory stressor, electric foot-shock. Using the tail-cuff method of determining SBP, the results of Experiment 1 replicated the previous finding that on the second and subsequent exposures, repeated defeat is followed by an acute decrement in SBP (30-40 mm Hg in magnitude). In contrast, repeated exposures to foot-shock were followed by acute increases in SBP (20-40 mm Hg) and in heart rate (HR). In Experiment 2, mean arterial blood pressure (MAP) and HR were measured directly from chronically cannulated male S/JR rats after defeat or exposure to foot-shock: again, defeated males exhibited an acute decrease in MAP, whereas the MAP of rats exposed to foot-shock tended to increase. In Experiment 3 we varied the parameters of shock intensity and the social context of shock exposure. Male S/JR rats exposed to more intense foot-shock than in the previous experiments or to foot-shock while paired with one of the resident attacker rats all exhibited acute increases in SBP. The results of these experiments indicate that CV response to defeat may be qualitatively different from CV response to foot-shock.

Aggression↗
PubMed1987

Acute stress increases plasma concentrations of atrial natriuretic peptides.

5 min exposure of inbred Maudsley Reactive male rats to intermittent foot-shock resulted in an approximate doubling of plasma atrial natriuretic peptides ANP (Control grp mean = 62.12 +/- 8.74; Stressed grp mean = 128.70 +/- 26.63 pg/ml) and 25 min exposure resulted in a three-fold increase (Stressed grp mean = 187.88 +/- 39.24 pg/ml). In the second experiment exposure of genetically heterogeneous Wistar male rats to 15 min of intermittent foot-shock produced a 10-fold increase in plasma ANP (Control grp mean = 45.76 +/- 6.05; Stressed grp mean = 471.20 +/- 58.49 pg/ml). The magnitude of the increase in plasma ANP produced by acute stress is as large as the increase caused by volume expansion and administration of various pharmacological agents and therefore delineation of biological role of ANP must take account of its potential role as a stress-hormone.

Animals↗
PubMed1986

Effects of social defeat on acute cardiovascular response in salt-sensitive and salt-resistant rats.

We studied the effects of social stress (SS) and a high salt diet on systolic blood pressure (SBP) and heart rate (HR): S/JR male rats (which exhibit marked elevations in SBP when placed on a high sodium diet) and R/JR male rats (which are resistant to the BP-elevating effects of a high sodium diet) were maintained on a low sodium diet (0.3% NaCl) or placed on a high sodium diet (8% NaCl). Within each dietary condition independent groups were either exposed to SS, by placement in the cage of a trained fighter male (Long-Evans breed) for 25 min, or exposed to no stress. The dietary regimen was imposed for 10 days with stress exposures on Days 1, 2, 3, 5, 7, and 9, with SBP and HR measured indirectly by tail plethysmography 3 min following exposure to SS. SS produced an acute decrease in SBP (20-30 mm Hg) in S/JR rats on the second and subsequent exposures, but did not affect HR. SS did not affect SBP of R/JR rats, but did produce a significant elevation of HR. Maintenance on the high sodium diet increased SBP in S/JR, but not R/JR, rats when it was measured on the eighth (no stress) day, but SS obscured the effects of diet on SBP on days when rats were stressed. Following exposure to attacks, defeated SS rats displayed an upright submissive posture relatively late during the first stress exposure when no change in SBP was observed after SS in S/JRs, but displayed the submissive posture immediately and with long duration on the second and subsequent exposures when a marked decrement in SBP was seen.

Aggression↗
PubMed1983

Genetic variation, chronic stress, and the central and peripheral noradrenergic systems.

Male rats from two inbred strains genetically selected for variation in response to stress were exposed for 9 consecutive days to 50 min of intermittent foot shock and killed 24 h after the last stress session. Maudsley Nonreactive (MNRA/Har) rats, genetically selected for decreased reactivity to stress, exhibited a significantly greater elevation (114% above control levels) in tyrosine hydroxylase activity in the locus ceruleus after chronic stress than Maudsley Reactive (MR/Har) animals (63% above control levels), genetically selected for heightened reactivity to stress. In the peripheral noradrenergic system, chronic stress produced an increase in norepinephrine (NE) content of small intestine and submaxillary gland of MNRA/Har rats, whereas chronic stress had no effect on NE content of these same tissues in MR/Har animals. These results are consistent with the proposition that genetic selection for variation in susceptibility to stress has altered the capacity of the central and peripheral noradrenergic system to adapt to chronic stress.

Adrenal Glands↗
PubMed1982

Cardiac beta-receptor variation in rat strains selectively bred for differences in susceptibility to stress.

The radioligand 3H-DHA was used to estimate the density and affinity of cardiac beta-receptors in rat strains selectively bred for differences in response to stress. Maudsley Reactive rats selected for heightened reactivity to stress had a greater density of beta-adrenergic binding in cardiac membranes than rats of two genetically distinct Maudsley Non-Reactive strains selected for decreased reactivity to stress, and compared with one of these Non-Reactive strains the MNR/Har, increased affinity for 3H-DHA. Together with previous findings the present results demonstrate a negative correlation between estimates of basal sympathetic activity on the on hand, and post-synaptic beta-receptors in heart on the other, that are consistent with the notion that these receptor alterations have occurred as a result of long-term differences in pre-synaptic release of transmitter. The Maudsley strains may, therefore, provide a useful model for the study of beta-adrenergic receptors as a physiological locus for regulation of end-target responsiveness to sympathetic stimulation.

Animals↗
PubMed1982

Tryptophan availability, central serotonergic function and methionine sulphoximine-induced convulsions.

A convulsant dose (100 mg/kg) of l-methionine-RS-sulphoximine (MSO) produced temporally correlated decreases in central 5-hydroxytryptamine (5-HT) and plasma and brain tryptophan (TRY) concentrations in C57BL/6J mice. In contrast, a subconvulsant dose of MSO (50 mg/kg) had no effect on central 5-HT levels and only decreased brain tryptophan at one time-point after its administration. The pattern of findings suggests that the decrease in central 5-HT levels resulting from a convulsant dose of MSO is related to an impairment in 5-HT synthesis resulting from a restriction of tryptophan availability. Administration of 25 mg/kg and 100 mg/kg doses of l-tryptophan with convulsant doses of MSO significantly increased seizure latency. It is suggested that the central 5-HT system modulates the expression of MSO-induced seizures.

Animals↗