{"id":1608,"date":"2020-02-21T17:25:51","date_gmt":"2020-02-21T09:25:51","guid":{"rendered":"http:\/\/www.bioactivescreeninglibrary.com\/?p=1608"},"modified":"2022-01-07T10:56:16","modified_gmt":"2022-01-07T02:56:16","slug":"increase-functional-capillary-density-flow-microcirculation","status":"publish","type":"post","link":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/2020\/02\/21\/increase-functional-capillary-density-flow-microcirculation\/","title":{"rendered":"There was no increase in the functional capillary density or flow within the microcirculation"},"content":{"rendered":"<p>This is in line with previous experimental work that demonstrated the protective effect of calcitriol in human endothelial cells cultured with AGE products. In our study, bone mineral parameters, kidney function, C reactive protein, blood pressure and aPWV were similar at 6 month follow up suggesting that functional changes to the microcirculation occurred independently of these parameters, adding strength to the argument that ergocalciferol may have a specific mechanism of action within the microcirculation. In contrast to other studies, proteinuria was unaffected in the ergocalciferol group although the differences in vitamin D compounds, dose schedule, study duration and populations between those studies and ours may explain this difference. aPWV did not decrease in line with the reduction in pulse pressure and this finding may reflect the short duration of the study. Studies with a longer follow up duration are more likely to demonstrate a fall in pulse wave velocity which may occur after a reduction in pulse pressure After 6 months of therapy with ergocalciferol. This implies that the observed improvements in endothelium dependent microcirculatory function did not involve the recruitment of extra functionally relevant capillaries or changes in blood flow but rather that the endothelium dependent function of the existing microcirculatory network was improved by the direct effect of ergocalciferol. This hypothesis is supported by the results of parallel in vitro experiments in which ergocalciferol, in a dose dependent manner, upregulated eNOS expression measured by RT-PCR. Nitric oxide generation compared to vehicle was numerically but not statistically significantly increased with low dose ergocalciferol but was significantly increased with high dose ergocalciferol. This suggests that higher doses of ergocalciferol are required to increase the functional effect of ergocalciferol on the endothelium and therefore that there may be a threshold 25 D concentration above which the maximum effects of ergocalciferol on the microcirculation are achieved. The present study is the first of its kind to explore the effect of vitamin D on microcirculatory function in patients with CKD and concomitant vitamin D deficiency. The exclusion of patients with diabetes mellitus allowed us to evaluate the effect of ergocalciferol on the microcirculation in CKD without the potentially confounding effect of diabetes on endothelial function. Prospective studies of the effect of vitamin D therapy in patients with CKD have so far failed to show a beneficial effect of vitamin D on endpoints <a href=\"http:\/\/www.abmole.com\/products\/pazopanib.html\">GW786034<\/a> including LVMI, aPWV, blood pressure and inflammatory biomarkers. The effect of nutritional vitamin D compounds on endothelial biomarkers and conduit artery endothelial function in kidney disease has been evaluated in two studies which have produced conflicting results. Marckmann et al. compared the effect of 8 weeks of 40,000 IU of weekly cholecalciferol compared to a placebo in patients with both CKD and ESKD treated with haemodialysis.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>This is in line with previous experimental work that demonstrated the protective effect of calcitriol in human endothelial cells cultured with AGE products. In our study, bone mineral parameters, kidney function, C reactive protein, blood pressure and aPWV were similar at 6 month follow up suggesting that functional changes to the microcirculation occurred independently of &hellip; <a href=\"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/2020\/02\/21\/increase-functional-capillary-density-flow-microcirculation\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;There was no increase in the functional capillary density or flow within the microcirculation&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1608"}],"collection":[{"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/comments?post=1608"}],"version-history":[{"count":1,"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1608\/revisions"}],"predecessor-version":[{"id":1609,"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1608\/revisions\/1609"}],"wp:attachment":[{"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/media?parent=1608"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/categories?post=1608"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www.bioactivescreeninglibrary.com\/index.php\/wp-json\/wp\/v2\/tags?post=1608"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}