Reduced adenosine A(2a) receptor-mediated efferent arteriolar vasodilation contributes to diabetes-induced glomerular hyperfiltration
2015 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 87, no 1, 109-115 p.Article in journal (Refereed) Published
Diabetes is associated with increased risk for development of kidney disease, and an increased glomerular filtration rate is an early indication of altered kidney function. Here we determine whether reduced adenosine A(2a) receptor-mediated vasodilation of the efferent arteriole contributes to the increased glomerular filtration rate in diabetes. The glomerular filtration rate, renal blood flow, and proximal tubular stop flow pressure were investigated in control and streptozotocin-diabetic rats during baseline and after administration of the adenosine A(2a) receptor antagonist ZM241385 or the adenosine A(2a) receptor agonist CGS21680. The diabetes-induced glomerular hyperfiltration was reduced by 24% following A(2a) receptor stimulation but was unaffected by A(2a) receptor inhibition. Contrarily, glomerular filtration rate in controls increased by 22% after A(2a) receptor inhibition and was unaffected by A(2a) stimulation. The increased glomerular filtration rate after A(2a) receptor inhibition in controls and decreased glomerular filtration rate after A(2a) receptor activation in diabetics were caused by increased and decreased stop flow pressure, respectively. None of the interventions affected renal blood flow. Thus, the normal adenosine A(2a) receptor-mediated tonic vasodilation of efferent arterioles is abolished in the diabetic kidney. This causes increased efferent arteriolar resistance resulting in increased filtration fraction and hyperfiltration.
Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Hybrid Model Option A , 2015. Vol. 87, no 1, 109-115 p.
diabetes mellitus; glomerular filtration rate; glomerular hyperfiltration; renal hemodynamics
IdentifiersURN: urn:nbn:se:liu:diva-113735DOI: 10.1038/ki.2014.219ISI: 000346977900014PubMedID: 24940797OAI: oai:DiVA.org:liu-113735DiVA: diva2:784591
Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation2015-01-302015-01-292015-01-30