Induced-hypercholesterolemia as a probable cause of alterations in pulse pressure in wistar kyoto rats

Background: The involvement of hypercholesterolemia in cardiovascular disorders has been widely researched but the impact on the specific cardiovascular (CV) indices following remodeling and cardiac malfunction remain to be fully elucidated. The aim this research is intended to further the understanding of cardiovascular function under hypercholesterolemic condition in mammals and serve as a guide to pharmaceutical formulation and medical interventions. Methods: The telemetry technique was used to investigate the cardiovascular dysfunctions in induced hypercholesterolemia in Wistar Kyoto (WKY) rats. Methods for this investigation include: inducing hypercholesterolemic condition in Wistar Kyoto rats through diet; measuring the blood cholesterol levels of the experimental animals; measuring cardiovascular indices in conscious rats to establish vascular dysfunction and/or cardiac malfunction. Results: Our study showed that pulse pressure decreases in experimental WKY rats with increasing cholesterol content in the diet. It also shows that diet related pulse pressure decrease occurs in both low and high animal activities. The pulse pressure was reduced at both low and high animal activities in the 2% cholesterol diet (N=6) when compared to control (N=4) and 1% cholesterol diet (N=7). All results presented were statistically significant at a P value < 0.05. Our study has shown that pulse pressure (PP) declined significantly in the 2% cholesterol loaded diet, but not in the 1% diet. We also observed that in overall, the 1% diet group maintained close to normal cardiovascular indices compared to the control and 2%. Conclusion: Our results show that a high cholesterol diet may have negatively impacted the cardiac function more than the vascular function.Keywords: hypercholesterolemia, remodeling, vascular, pharmaceutical, dysfunctions, cardiovascular, telemetry, WKY rat

Gene Expression Profiling on Global cDNA Arrays Gives Hints Concerning Potential Signal Transduction Pathways Involved in Cardiac Fibrosis of Renal Failure

Cardiac remodelling with interstitial fibrosis in renal failure, which so far is only poorly understood on the molecular level, was investigated in the rat model by a global gene expression profiling analysis. Sprague–Dawley rats were subjected to subtotal nephrectomy (SNX) or sham operation (sham) and followed for 2 and 12 weeks, respectively. Heart-specific gene expression profiling, with RZPD Rat Unigene-1 cDNA arrays containing about 27 000 gene and EST sequences revealed substantial changes in gene expression in SNX compared to sham animals. Motor protein genes, growth and differentiation markers, and extracellular matrix genes were upregulated in SNX rats. Obviously, not only genes involved in cardiomyocyte hypertrophy, but also genes involved in the expansion of non-vascular interstitial tissue are activated very early in animals with renal failure. Together with earlier findings in the SNX model, the present data suggest the hypothesis that the local renin–angiotensin system (RAS) may be activated by at least two pathways: (a) via second messengers and Gproteins (short-term signalling); and (b) via motor proteins, actins and integrins (longterm signalling). The study documents that complex hybridization analysis yields reproducible and promising results of patterns of gene activation pointing to signalling pathways involved in cardiac remodelling in renal failure. The complete array data are available via http://www.rzpd.de/cgi-bin/services/exp/viewExpressionData.pl.cg

Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca 2+ levels in endothelial cells

10.1530/JME-11-0082Journal of Molecular Endocrinology473315-326JMLE