Search PubMed⌕ Search

Biomedical subjects

R McCarty

Publications and source records attributed to R McCarty.

At least 109 records · Page 6Linked to original sources

Difference in choline acetyltransferase but similarities in catecholamine biosynthetic enzymes in brains of two rat strains differing in their response to stress.

Rats of the Wistar-Kyoto (WKY) strain are more reactive to stress than Brown-Norway (BN) rats as adjudged by their behavioral and plasma catecholamine (CA) responses to stress. Contrary to the strain differences existing in the periphery, brain CA and their biosynthetic enzyme activities were found to be similar in both strains before and after immobilization stress. However, as in the periphery, choline acetyltransferase (CAT) activity was higher in brains of WKY rats. The results suggest that: (1) peripheral and central CA systems may be under different genetic control mechanisms, and (2) strain differences in CAT activity may reflect differences in cholinergic systems both in the brain and periphery, which may be important in the behavioral differences observed.

Animals↗

Effects of handling during infancy on the sympathetic-adrenal medullary system of rats.

We examined the effects of daily handling and maternal separation (5 min per day) on the responsiveness of the sympathetic-adrenal medullary system of Sprague-Dawley rats before weaning and in adulthood. Plasma levels of norepinephrine (derived primarily from sympathetic nerves) and epinephrine (released from the adrenal medulla) were elevated in handled pups compared to unhandled controls at 14 and 18 days of age but not at 6 and 10 days of age. When tested in adulthood, previously handled and control rats did not differ with respect to basal or stress-induced increments in plasma levels of norepinephrine and epinephrine. These results indicate that brief daily episodes of handling and maternal separation are attended by an increase in sympathetic-adrenal medullary tone in 14-18-day-old rats. However, the enhanced response of the sympathetic-adrenal medullary system of separated rats may not persist into adulthood.

Adrenal Medulla↗

Differential behavioral responses of spontaneously hypertensive (SHR) and normotensive (WKY) rats to d-amphetamine.

A comparison was made in the behavioral responses of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats to d-amphetamine. Animals were tested at a young age (6 weeks) to minimize the effects of elevated blood pressure on drug responsiveness. SHR rats were more active than WKY rats after injections of 1.0, 2.0, and 4.0 mg/kg d-amphetamine. A significant strain difference in stereotypy was also noted; rearing occurred in SHR rats while lateral or vertical head movements (head waving) occurred in WKY rats. The lack of significant strain differences in the behavioral responses of rats to apomorphine, a direct acting dopamine agonist, suggested that the differential behavioral responses to d-amphetamine were not a result of differences between strains in receptor sensitivity. Pretreatment of rats with reserpine eliminated the strain differences in behavioral responses to d-amphetamine. Pretreatment of rats with alpha-methyl-p-tyrosine prior to administration of d-amphetamine elminated the strain differences in stereotyped behavior; however, WKY rats remained less active than SHR rats. Pretreatment of SHR rats with parachlorophenylalanine had no effect on the behavioral responses to d-amphetamine. In contrast, pretreatment of WKY rats with parachlorophenylalanine resulted in an increase in rearing and a decrease in head waving following an injection of d-amphetamine. These findings suggest that the differences in responses to d-amphetamine of SHR and WKY rats are due in part to variations in the activities of central catecholaminergic and serotonergic neurons.

Animals↗

Linkage analysis between the major histocompatibility system and insulin-dependent diabetes in families with patients in two consecutive generations.

We have histocompatibility (HLA) genotyped 28 families with insulin-dependent diabetics in two or more consecutive generations, usually parent and child. This strategy of ascertainment was used to maximize the likelihood of obtaining a homogeneous type of disease within a family, and an autosomal dominant mode of inheritance. 76 diabetics and 169 nondiabetics were studied in these families. The frequencies of the antigens Dw3 and Dw4, and the genotype Dw3/Dw4 among the diabetics are 59, 68, and 30%, respectively, as compared with 15, 12, and 2% in normal controls, and 43, 41, and 10% in the nondiabetic relatives of the diabetics. Dw2 is present in only one diabetic (4%), as compared with 18% in normal controls and 17% in nondiabetic relatives.HLA haplotype concordance was analyzed for sib pairs in relation to the haplotype shared by the affected parent/child pair, and for the diabetic sib pairs within each sibship. The results failed to reveal deviations in the expected HLA haplotype assortment. Assuming an autosomal dominant mode and several penetrance levels, linkage analysis between the HLA and diabetes was performed. The total lod score is 0.37 for a recombination fraction of 0.29 at 50% penetrance. Although the linkage and concordance analysis results are inconclusive, they seem to be different from those reported by us for families with normal parents and two or more diabetic sibs. Because ascertainment biases may have influenced these results in an unquantifiable manner, it is not certain whether the two types of families are genetically different. However, the marked difference in the lod scores for the 50% penetrant autosomal recessive model between the two types of families is compatible with a genetic dissimilarity between them. The high frequency of the Dw3 and Dw4 antigens, the Dw3/Dw4 genotype, and the decreased frequency of Dw2, however, indicate the existence of two or more important diabetic genetic factors associated with the D region of the HLA in these families.

Diabetes Mellitus, Type 1↗

Plasma catecholamines in human and experimental hypertension.

Plasma levels of norepinephrine reflect the rate of its release from sympathetic nerves. In patients with hypertension and in spontaneously hypertensive (SHR) rats basal plasma NE levels are normal. SHR rats are abnormally reactive to stress, as are the normotensive (WKY) strain from which they were derived. The amounts of NE released by sympathetic stimulation are similar in pithed SHR and WKY rats, but SHR rats have greater blood pressure responses. This may be due to diminished beta-adrenoceptor-mediated vasodilation in young SHR rats and structural changes in arterioles of older SHR rats. It is concluded that in SHR rats separate abnormalities of centrally-mediated responses to stress and of peripheral sensitivity to catecholamines contribute to the development and maintenance of elevated blood pressure.

Aging↗

Patterns of behavioral development in spontaneously hypertensive rats and Wistar-Kyoto normotensive controls.

We have examined the behavior of spontaneously hypertensive (SHR) rats and stroke-prone hypertensive (SP-SHR) male rats during the development and maintenance of elevated blood pressure and compared this pattern with age- and gender-matched normotensive (WKY) rats of the same Wistar-Kyoto strain as controls. Rats of each strain (n = 10/age group) were isolated in individual cages and observed for 60 min at 3,4,6,8,10, or 20 weeks of age using a scan sampling technique. At all ages SHR rats were significantly more active than WKY rats whereas SP-SHR rats were intermediate in level of activity. In a 2nd series, activity of male rats of each strain was monitored continuously for 24 hr in the home cage. No strain differences in amount or pattern of total daily activity were evident at either 4-6 or 16-18 weeks of age. These results indicate that SHR rats are more reactive to environmental change, but the intermediate level of activity of SP-SPHR rats suggests that this response is not related to the degree of blood pressure elevation,

Age Factors↗

Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress.

Blood pressure, heart rate, and circulating levels of norepinephrine, epinephrine, and corticosterone were measured before and during the first or seventh period of immobilization stress (150 min per day) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive male rats. A catheter was inserted into the tail artery of each rat to permit direct measurement of blood pressure and heart rate and serial sampling of blood in conscious, unhandled animals. During the first immobilization, SHR rats had significantly higher circulating levels of norepinephrine, epinephrine, and corticosterone than did WKY rats. One day after the sixth immobilization, basal levels of norepinephrine and epinephrine were significantly higher and mean blood pressure was significantly lower in repeatedly stressed SHRs compared to unstressed SHRs. In addition, adaptation to the repeated stress in SHRs was attended by reduced adrenomedullary secretion and an increased blood pressure response. These results demonstrate that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.

Animals↗