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SHR Rats (shr + rat)
Selected AbstractsMarker-assisted dissection of genetic influences on motor and neuroendocrine sensitization to cocaine in ratsGENES, BRAIN AND BEHAVIOR, Issue 3 2009L. F. Vendruscolo This study investigated genetic influences on behavioral and neuroendocrine responses to cocaine sensitization. We used male and female rats of the inbred strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which display genetic differences in stress-related responses. The influence of two quantitative trait loci (QTL; Ofil1 and Ofil2 on chromosomes 4 and 7), which modulate stress reactivity in rats, on the effects of cocaine was also investigated through the use of recombinant lines (derived from a LEW × SHR intercross) selected by their genotype at Ofil1 and Ofil2. Animals were given repeated cocaine or saline injections and tested for locomotion (induction of sensitization). Two weeks later, all animals were challenged with cocaine, and locomotion and corticosterone levels were measured (expression of sensitization). Results indicated that male SHR rats showed more behavioral sensitization than LEW rats, whereas no strain differences in sensitization were seen among females. When challenged with cocaine, LEW and SHR rats of both sexes pretreated with cocaine showed behavioral sensitization compared with saline pretreated animals; however, only LEW rats displayed an increase in the corticosterone levels. Ofil1 was found to influence the induction of sensitization in males and Ofil2 modulated the locomotor effect of cocaine in females. This study provides evidence of a genotype-dependent relationship between the induction and expression of cocaine sensitization, and between the behavioral and neuroendocrine responses induced by cocaine. Moreover, the Ofil1 and Ofil2 loci may contain one or more genes that control the behavioral effects of cocaine in rats. [source] Evidence for a female-specific effect of a chromosome 4 locus on anxiety-related behaviors and ethanol drinking in ratsGENES, BRAIN AND BEHAVIOR, Issue 6 2006L. F. Vendruscolo Previous studies using the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) led to the mapping of two quantitative trait loci, named Ofil1 (on chromosome 4 of the rat) and Ofil2 (on chromosome 7), for open-field inner locomotion, a behavioral index of anxiety. Studies using other strains showed that the region next to Ofil1 influences measures of not only anxiety but also ethanol consumption. In view of the high prevalence of psychiatric disorders such as anxiety and alcoholism, as well as the comorbidity between them, the present study was designed to better characterize the contribution of these two loci to complex emotional and consummatory responses. Rats deriving from an F2 intercross between the LEW and the SHR strains were selected according to their genotype at markers flanking the loci Ofil1 and Ofil2 and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating four genotypic combinations. These selected animals as well as purebred LEW and SHR rats of both sexes were submitted to a battery of tests including measures of locomotor activity, anxiety, sweet and bitter taste reinforcement and ethanol intake. Lewis rats displayed more anxiety-like behavior and less ethanol intake than SHR rats. Ofil1 (on chromosome 4) affected both the activity in the center of the open field and ethanol drinking in females only. These results suggest that Ofil1 contains either linked genes with independent influences on anxiety-related responses and ethanol drinking or a pleiotropic gene with simultaneous effects on both traits. [source] Zoledronic acid improves femoral head sphericity in a rat model of perthes diseaseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2005David G. Little Abstract We hypothesized that the bisphosphonate zoledronic acid (ZA) could improve femoral head sphericity in Perthes disease by changing the balance between bone resorption and new bone formation. This study tests the effect of ZA in an established model of Perthes disease, the spontaneously hypertensive rat (SHR). One hundred and twenty 4-week old SHR rats were divided into three groups of 40: saline monthly, 0.015 mg/kg ZA weekly, or 0.05 mg/kg ZA monthly. At 15 weeks DXA measurements documented that femoral head BMD was increased by 18% in ZA weekly and 21% in ZA monthly compared to controls (p < 0.01). Femoral head sphericity in animals with osteonecrosis was improved in ZA-treatment groups (p < 0.01) as measured by epiphyseal quotient (EQ). The proportion of "flat" heads (EQ ± 0.40) was significantly reduced from 32% in saline-treated animals to 12% in weekly ZA and 3% in monthly ZA (p < 0.01). Histologically there was a similar prevalence of osteonecrosis in all groups. The prevalence of ossification delay was significantly reduced by ZA treatment (p < 0.01). Zoledronic acid favorably altered femoral head shape in this spontaneous model of osteonecrosis in growing rats. Translation of these results to Perthes disease could mean that deformity of the femoral head may be modified in children, perhaps reducing the need for surgical intervention in childhood and adult life. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Arylazoamidoximes and Related Compounds as NO-modulatorsARCHIV DER PHARMAZIE, Issue 1 2010Alexander Schröder Abstract Three amidinoarylhydrazines 1, three arylazoamidines 2, and nine arylazoamidoximes 3 have been synthesized and investigated for their potential to function as nitric oxide (NO) modulators. In-vitro studies demonstrated that 2 and 3 inhibited platelet aggregation (2c, IC50 = 3 ,M) which could also be shown in vivo by inhibition of thrombus formation in arterioles (3a, 22%). Moreover, for all compounds antihypertensive effects were examined in vivo with SHR rats, with 2a being the most potent candidate by lowering blood pressure by 19%. However, no common underlying mechanism of action could be shown. Some of these compounds released HNO non-enzymatically. Incubations with NO synthase isoforms (NOSs) revealed, that compounds 1 to 3 were weak substrates for NOSs but arylazoamidoximes 3 remarkably elevated the NOSs activity in the presence of L -arginine (3h, up to fivefold). In addition, we examined effects on arginase and dimethylarginine dimethylaminohydrolase (DDAH), two further enzymes involved in the complex regulation of NO biosynthesis, to elucidate whether the observed in-vivo effects can be traced back to their modulation. Furthermore, the metabolic fate of arylazoamidoximes 3 was addressed by investigation of a possible N -reductive biotransformation. In summary, novel NO-modulating compound classes are presented, among which arylazoamidoximes 3 are potent activators of NOS isoforms, and arylazoamidines 2 exert in-vivo effects by unknown mechanisms. [source] Effects of lipopolysaccharide on vascular reactivity and mortality in ratsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 5-6 2002J. P. L. Nunes Summary 1 The effects of intraperitoneal (i.p.) lipopolysaccharide on vascular reactivity to noradrenaline in rat aorta under different conditions of passive tension, as well as on mortality in normotensive and hypertensive rats, were studied. 2 Concentration,response curves to noradrenaline were obtained in aorta rings, at two levels of passive tension: 3 and 0.5 g, from control and lipopolysaccharide-treated Wistar rats. Contractile responses were expressed as percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a resting tension of 2 g. The maxima were significantly larger (P < 0.05) at 3 g than at 0.5 g in both groups of rats: 117.8 vs. 62.3%, respectively, for control animals; 85.8 vs. 32.5%, respectively, for lipopolysaccharide-treated rats. 3 The 24-h mortality after the i.p. administration of lipopolysaccharide was lower in spontaneously hypertensive rats (1/12; 8%), when compared with control Wistar,Kyoto rats (5/11; 45%). However, mortality was higher in Wistar,Kyoto made hypertensive by 8-day administration of corticosterone (6/6; 100%). 4 We conclude that a differential sensitivity to noradrenaline of aortic smooth muscle at two different levels of passive tension is still present in lipopolysaccharide-treated animals. Chronic hypertension in SHR rats is associated with resistance to the lethal effects of lipopolysaccharide, whereas abrupt-onset hypertension induced by corticosterone leads to an increased mortality. 5 These results are compatible with the myofibrillary hypothesis, which explains vascular hyper-reactivity in chronic arterial hypertension, by postulating that a more favourable relative position (and/or proportion) for actin and myosin occurs, whereas in states of vascular hypo-reactivity, such as vasodilatory shock, the opposite phenomenon may exist. [source] The ,-adrenoceptor antagonist, zolertine, inhibits ,1D- and ,1A-adrenoceptor-mediated vasoconstriction in vitroAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2000M. Ibarra 1 The antagonist effect of zolertine (4-phenyl-1-[2-(5-tetrazolyl)ethyl]piperazine trihydrochloride), on vascular contraction elicited by noradrenaline in aorta, carotid (,1D-adrenoceptors), mesenteric (,1A/D-adrenoceptors) and caudal arteries (,1A-adrenoceptors) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats and rabbit aorta (,1B-adrenoceptors), was investigated in endothelium-denuded arterial rings. 2 The selective ,1D-adrenoceptor agonist, noradrenaline, elicited concentration-dependent contractions in all arterial rings from both species. Noradrenaline selectivity was: carotid=aorta>>.Gt;mesenteric=rabbit aorta>caudal arteries. 3 The contractile responses induced by noradrenaline were competitively antagonized by zolertine in rat carotid and aorta arteries, yielding pA2 values of WKY, 7.48±0.18; SHR, 7.43±0.13 and WKY, 7.57±0.24; SHR, 7.40±0.08, respectively. Zolertine was a non-competitive antagonist in some blood vessels as Schild plot slopes were lower than unity. The pKb estimates for zolertine were WKY, 6.98±0.16; SHR, 6.81±0.18 in the mesenteric artery, WKY, 5.73±0.11; SHR, 5.87±0.25 in the caudal artery and 6.65±0.09 in rabbit aorta. 4 Competition binding experiments using the ,1-adrenoceptor antagonist [3H]prazosin showed a zolertine pKi of 6.81±0.02 in rat liver (,1B-adrenoceptors) and 6.35±0.04 in rabbit liver (,1A-adrenoceptors) membranes. 5 Zolertine showed higher affinity for ,1D-adrenoceptors compared to ,1A-adrenoceptors, while it had an intermediate affinity for ,1B-adrenoceptors. The ability of the ,1-adrenoceptor antagonist zolertine to block ,1D-adrenoceptor-mediated constriction in different vessels of WKY and SHR rats may explain its antihypertensive efficacy despite its low order of potency. [source] MECHANICAL BONE PROPERTIES OF OBESE MODEL SHR/NDmcr-cp RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007Naomi Nishii SUMMARY 1High-blood pressure or diabetes may be related to the loss of bone mass or the development of osteoporosis. We examined the mechanical bone properties of the SHR/NDmcr-cp (SHR-cp) rat, an obese strain that develops hypertension, hyperlipidaemia and insulin-independent diabetes. 2The mechanical properties of the femur of 22-week-old Wistar-Kyoto (WKY) and SHR-cp rats were measured by Peng's three-point bending procedure modified by Shintani. Femurs were then defatted and dried. After weighing, the dried bones were ashed and the ash was weighed. The values of the dry weight, ash weight and ash weight/dry weight (%) were used as a description of the physical parameters of the bone. 3All values of stiffness, strength, toughness and ductility in SHR-cp were significantly lower than those of WKY rats (P < 0.05). The value of ash weight/dry weight (%) was lower in SHR-cp rats (P < 0.01). These results showed that bone fragility was greater in SHR-cp rats, indicative of osteopenia. [source] | |||||||||||||