uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Adenosine A1 receptor-dependent and independent pathways in modulating renal vascular responses to angiotensin II
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Karolinska Institutet. (Dept Physiology & Pharmacology)
Karolinska Institutet. (Dept Physiology & Pharmacology)
Charité-Universitätsmedizin Berlin, Germany. (Institute of Vegetative Physiology)
Show others and affiliations
2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 1, 268-276 p.Article in journal (Refereed) Published
Abstract [en]

AIM: Renal afferent arterioles are the effector site for autoregulation of glomerular perfusion and filtration. There is synergistic interaction between angiotensin II (ANG II) and adenosine (Ado) in regulating arteriolar contraction, however, the mechanisms are not clear. In this context, this study investigated the contribution of A1 receptor dependent and independent signaling mechanisms.

METHODS: Isolated perfused afferent arterioles from transgenic mice (A1+/+ and A1-/-) were used for vascular reactivity studies. Cultured vascular smooth muscle cells (VSMC) were used for phosphorylation studies of signaling proteins that induce arteriolar contraction.

RESULTS: Maximal arteriolar contraction to ANG II was attenuated in A1-/- (22%) compared with A1+/+ (40%). Simultaneous incubation with low dose Ado (10-8 mol/L) enhanced ANG II-induced contraction in A1+/+ (58%), but also in A1-/- (42%). An Ado transporter inhibitor (NBTI) abolished this synergistic effect in A1-/-, but not in wild-type mice. Incubation with Ado+ANG II increased p38 phosphorylation in aortic VSMC from both genotypes, but treatment with NBTI only blocked phosphorylation in A1-/-. Combination of ANG II+Ado also increased MLC phosphorylation in A1+/+ but not significantly in A1-/-, and NBTI had no effects. In agreement, Ado+ANG II-induced phosphorylation of p38 and MLC in rat preglomerular VSMC was not affected by NBTI. However, during pharmacological inhibition of the A1 receptor simultaneous treatment with NBTI reduced phosphorylation of both p38 and MLC to control levels.

CONCLUSION: Interaction between ANG II and Ado in VSMC normally involves A1 receptor signaling, but this can be compensated by receptor independent actions that phosphorylate p38 MAPK and MLC.

Place, publisher, year, edition, pages
2015. Vol. 213, no 1, 268-276 p.
Keyword [en]
afferent arteriole, microcirculation, vascular smooth muscle cell, kidney, p38 MAP kinase, myosin light chain
National Category
URN: urn:nbn:se:uu:diva-230758DOI: 10.1111/apha.12399ISI: 000346475000021OAI: oai:DiVA.org:uu-230758DiVA: diva2:741733
Available from: 2014-08-28 Created: 2014-08-28 Last updated: 2015-01-26Bibliographically approved
In thesis
1. Local Purinergic Control of Arteriolar Reactivity in Pancreatic Islets and Renal Glomeruli
Open this publication in new window or tab >>Local Purinergic Control of Arteriolar Reactivity in Pancreatic Islets and Renal Glomeruli
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Local control of regional blood flow is exerted mainly through the arterioles. An adequate minute-to-minute regulation of blood perfusion of the kidney and the pancreas is obtained by the modulation of arteriolar reactivity, which will influence the organ function. The importance of purinergic signaling in this concept has been addressed, with special emphasis on the role of the adenosine A1 receptor. The effects of adenosine on two specialized vascular beds, namely the renal glomerulus and the pancreatic islets, have been examined. Characteristic for these regional circulations is their very high basal blood flow, but with somewhat different responses to vasoconstrictor and vasodilator stimuli. By adapting a unique microperfusion technique it was possible to separately perfuse isolated single mouse arterioles with attached glomeruli or pancreatic islets ex vivo. Microvascular responses were investigated following different additions to the perfusion fluid to directly examine the degree of dilation or constriction of the arterioles. This has been performed on transgenic animals in this thesis, e.g. A1 receptor knockout mice. Also effects of P2Y receptors on islet arterioles were examined in both normoglycemic and type 2 diabetic rats. Furthermore, interference with adenosine transport in glomerular arterioles were examined.. Our studies demonstrate important, yet complex, effects of adenosine and nucleotide signaling on renal and islet microvascular function, which in turn may influence both cardiovascular and metabolic regulations. They highlight the need for further studies of other purinergic receptors in this context, studies that are at currently being investigated.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 65 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1024
afferent arteriole, islet arteriole, adenosine, A1 receptor, ATP, P2Y receptor, microperfusion, angiotensin II, type 2 diabetes, hypertension, oxidative stress, nitric oxide, tubuloglomerular feedback
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-230770 (URN)978-91-554-9018-8 (ISBN)
Public defence
2014-10-16, C2: 301, BMC, Husargatan 3, Uppsala, 13:00 (English)
Available from: 2014-09-24 Created: 2014-08-28 Last updated: 2015-01-22

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Gao, XiangPersson, Erik
By organisation
Department of Medical Cell Biology
In the same journal
Acta Physiologica

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 288 hits
ReferencesLink to record
Permanent link

Direct link