Prevention of myocardial disease in JCR:LA-corpulent rats by running

Russell, James C.; Amy, R.M.; Manickavel, V.; Dolphin, Peter J.; Epling, W. Frank; Pierce, D.; Boer, Douglas P.

doi:10.1152/jappl.1989.66.4.1649

Cited by 43 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14 ' 23 Previous studies also revealed that lipoproteins could inactivate or inhibit EDRF release 24 -27 and that intensive physical activity could largely correct the lipid abnormalities of atherosclerosis-prone rats. 28 Therefore, the third possibility is that endurance-type exercise training may change the lipid pattern and consequently enhance EDRF release. However, whether this training-induced lipid pattern change causes any regional difference along the vasculature remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits.

Chen

1993

Arterioscler Thromb

View full text Add to dashboard Cite

To investigate whether exercise training can modulate endothelium-dependent vasorelaxation, male New Zealand White rabbits were divided into either control or training groups. The training animals were trained on a treadmill with a running speed of 0.88 km/hr on a 0° grade for 10-60 minutes/day, 5 days/week for 8 weeks. After exercise training, the resting heart rate was lowered (p<0.05). At the end of the experiments, three vessel segments, i.e., the thoracic aortas, the pulmonary arteries, and the common carotid arteries, were isolated and precontracted with norepinephrine. Acetylcholine-stimulated endothelium-derived relaxing factor (EDRF) release was assessed by bioassay in the presence of indomethadn (10~s M). Basal release of EDRF was examined by the addition of hemoglobin. In addition, the relaxing responses of the thoracic aortas and pulmonary arteries to A23187, a calcium ionophore, and to sodium nitroprusside, a direct vasodilator of vascular smooth muscle, were compared between control and trained groups to further investigate possible underlying mechanisms. The results indicated that after exercise training 1) both the thoracic aorta and pulmonary artery, but not the carotid artery, became more sensitive to acetylcholine-induced vasorelaxation; 2) no significant differences in basal release of EDRF between control and trained rabbits were observed; and 3) there were no significant differences in the vascular responses to A23187 or sodium nitroprusside between the two groups. Our data suggest that exercise training may enhance endothelium-dependent vasodilation to acetylcholine via the stimulated EDRF release and that this elevated sensitivity to acetylcholine may not be caused by the alteration of the relaxing response in vascular smooth muscle. (Arteriosclerosis and Thrombosis 1993;13:852-856) KEY WORDS • endurance exercise • endothelium • acetylcholine • rabbits • endotheliumderived relaxing factor

show abstract

Section: Discussionmentioning

confidence: 99%

Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits.

Chen

1993

Arterioscler Thromb

View full text Add to dashboard Cite

show abstract

“…910 Certainly, a number of experimental manipulations of the rats, including food restriction and intensive exercise, reduce both the plasma lipid and insulin concentrations. 21 However, the plasma VLDL levels of corpulent females are markedly higher than those of males, while their insulin resistance is much less severe. 910 There is evidence that both activity of and mRNA expression for glycerophosphate dehydrogenase are increased in the cp/cp rat (Shillabeer, Hornford, Russell, Wong, and Lau, unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Plasma lipid secretion and clearance in hyperlipidemic JCR:LA-corpulent rats.

et al. 1989

View full text Add to dashboard Cite

The JCR: LA-corpulent rat Is an obese, hyperlipidemic, hyperinsullnemlc strain that Is atherosclerosis-prone and develops myocardlal lesions. The hyperllpldemla Is due to elevated plasma levels of a large relatively triglycerlde-rich very low density lipoprotein (VLDL). Both corpulent and lean male and female rats were studied. Postheparln llpid clearance and apparent hepatic secretion rate after Triton WR1339 Inhibition of lipoproteln llpase were determined. The concentrations of cholesterol and cholesteryl esters were not significantly altered by either treatment TrlglycerIdes showed rapid postheparln clearance In corpulent rats. The apparent hepatic secretion rate was markedly higher In corpulent male rats than In lean male rats, and the rate in corpulent females was again higher, reflecting the higher serum trlglyceride concentrations In corpulent female rats. The relative secretion rate of C 4 8 trlglycerlde molecular species was lower than that of the C: 50 to C: 56 species, while the postheparln clearance of C 4 8 trlglycerlde molecular species was impaired compared to the C: 50 species and those with higher carbon numbers. This effect was more marked In the male than In the female corpulent rats. The results Indicate that VLDL hyperllpldemia In the corpulent rat Is due to hepatic hypersecretlon of VLDL and not to a defect in lipoproteln llpase. Further, the atherogenesls that Is characteristic of the corpulent male rat may be related to the differential metabolism of fatty acids. (Arteriosclerosis 9:869-876, November/December 1989) T he JCR: L A-corpulent rat incorporates the corpulent (cp) gene isolated by Koletsky. 1^ The original strain was derived from a cross of the spontaneously hypertensive (SHR) and Sprague-Dawley rat strains and was hypertensive, hyperlipidemic, and prone to a fulminant atherosclerosis. Hansen 3 incorporated the cp gene into two inbred strains, the SHR/N and the LA/N. Repeated backcrosses (more than 12 times) were made to the parent strains to give two congenic strains. Rats that are homozygous for the cp gene (cp/cp) are obese, while rats that are heterozygous (cp/+) or homozygous normal (+/+) are lean and indistinguishable from the parent strain. The LA/N-cp strain has been described by Elwood et al. 4 and studied as a model for obesity and the effects of high sugar intake. The SHR/N-cp rat is highly sensitive to dietary sucrose and is regarded as a model for the study of obesity and insulin resistance. 5In the course of the development of the LA/N-cp congenic strain, breeding stock from the fifth backcross was used to establish a colony in our laboratories. This colony differs from the fully congenic LA/N-cp and has recently been designated JCR: LA-cp. We have described this strain in previous publications.6 ' 7 The cp/cp male rats spontaneously develop both atherosclerotic and myocarFrom the Departments of Surgery and Pathology, University of Alberta, Edmonton, Alberta, and the Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada.This work was supp...

show abstract

“…15 Both treatments resulted in the elimination of large scarred myocardial lesions. These results are consistent with the proposal that the pathophysiological process leading to vascular and myocardial damage is initiated by high insulin levels or some related factor.…”

mentioning

confidence: 99%

“…Gas chromatographic analysis yields the concentration of free cholesterol, individual cholesterol esters, diacylglycerols, and ceramides of the phospholipids and triglycerides, with individual results by fatty acid carbon numbers. Thus the triglyceride molecular species may be specified according to their number of acyl carbon atoms 15 as follows: The results reported for cholesterol esters, phospholipids, and triglycerides represent the sum of the concentrations of the particular molecular species. We also report separately on the individual triglyceride molecular species in appropriate instances.…”

mentioning

confidence: 99%

Prevention of myocardial lesions in JCR:LA-corpulent rats by nifedipine.

et al. 1990

View full text Add to dashboard Cite

Male rats of the JCR LA-corpulent strain spontaneously develop atherosclerosis and myocardial lesions If corpulent. The corpulent rats exhibit a marked very low density hyperlipidemla and Insulin resistance. The incidence of both vascular and myocardial lesions correlates strongly with the hyperinsullnemia, but not with the hyperllpldemia. Corpulent male rats were chronically treated with nifedipine or acetylsallcytlc acid to explore the roles of smooth muscle spasm and platelet activity In Induction of the myocardial lesions. Acetylsalicylic acid treatment was associated with no significant changes In fasting glucose, Insulin, or lipld concentrations. Nifedipine caused no significant changes In glucose concentration but was associated with mildly Increased insulin levels. Treatment with nifedipine resulted In significant decreases In serum trlglycerlde concentrations. The decreases were confined to longer-chain trlacylglycerol molecular species with no change in the concentration of molecular species with 48 or 50 acyl carbon atoms. There was no effect on myocardial lesion frequency with acetylsalicylic acid treatment. In contrast, nifedipine prevented the development of old organized scarred lesions. This effect is similar to that seen with treatments that markedly reduce the Insulin resistance. These findings suggest that platelet-initiated thrombus formation Is not an Important factor In lesion formation In the JCRLA-cp rat, but that smooth muscle spasm Is probably Important (Arteriosclerosis 10:658-664, July/August 1990) O ne of the critical end points of atherosclerotic disease is the induction of ischemic myocardial lesions. These may vary from small discrete lesions with loss of myocytes and scarring to massive areas of infarction leading to rapid death. The precise sequence of mechanisms of events leading from the atherosclerotic lesion to myocardial damage is often not clear. The major possible mechanisms that have been discussed are simple occlusion of the artery by the atherosclerotic lesion, intramural hemorrhage leading to an enlarged lesion and occlusion, thrombus formation on the surface of the atherosclerotic lesion, and vasospasm induced or promoted by the vascular lesion. 12 The JCR:LA-corpulent rat is a unique strain that has been shown to spontaneously develop both atherosclerotic and ischemic myocardial lesions. 34 The substrain incorporates the corpulent (cp) gene first isolated by Koletsky 88 and later bred by Hansen 7 into two congenic strains, the LA/N-cp and SHR/N-cp. These strains have been described 89 and are regarded as models for the study of obesity. At the fifth backcross to the parent LA/N strain, a colony was established in our laboratories and at the seventh backcross, an analogous SHR/N-cp colony was established elsewhere. These two substrains have From the Departments of Surgery and Pathology, University of Alberta, Edmonton, Alberta, and the Department of Biochemistry, Dalhousle University, Halifax, Nova Scotia, Canada.This work was supported by the Alberta and Nova Scoti...

show abstract

Prevention of myocardial disease in JCR:LA-corpulent rats by running

Cited by 43 publications

References 0 publications

Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits.

Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits.

Plasma lipid secretion and clearance in hyperlipidemic JCR:LA-corpulent rats.

Prevention of myocardial lesions in JCR:LA-corpulent rats by nifedipine.

Contact Info

Product

Resources

About