Renal arterioles represent the most important effecter site in the control of renal perfusion and filtration. Adenosine (Ado), angiotensin II (Ang II) and nitric oxide (NO) interact in modulating arteriolar tone. The present work investigates the mechanism of this interaction. We tested the hypothesis that AT1 receptor (AT1AR) mediated NO release in isolated perfused afferent arterioles. Further, special attention was given to mechanisms of Ado-Ang II -interactions. We found (I) that Ang II specifically induces NO release via AT1AR in arterioles. The effect is important in view of high renin and Ang II concentrations in these vessels. (II) Ado modulates the Ang II response by acting on vasoconstrictor A1AR and vasodilator A2AR. Vice versa, Ang II critically enhances the constriction to Ado, which supports the assumption of its modulating action in the tubuloglomerular feedback (TGF). (III) The synergistic effect of Ang II and Ado on arteriolar contraction is concurrent with an increase in the cytosolic calcium. Further, (IV) Ado increases the calcium sensitivity of the contractile machinery in arteriolar smooth muscle cells most probably by enhancement of the phosphorylation of the myosin light chain regulatory unit. RhoA kinase, protein kinase C and p38 MAP are involved in the Ado effect, which is not receptor mediated and depends on the Ado uptake into vascular cells. Remarkably, the enhancing action of Ado is most likely limited to Ang II; since Ado does not influence endothelin-1 and norepinephrine induced contractions. These novel results extend our knowledge about the synergistic action of Ang II and Ado in the control of renal filtration. Ado, the key factor in mediation of the TGF, develops a significant vasoconstrictor action only in the presence of Ang II. On the other hand, the Ang II induced vasoconstriction is modulated by Ado via receptor and non-receptor mediated intracellular signaling pathways.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-7702 |
| Date | January 2007 |
| Creators | Lai, Enyin |
| Publisher | Uppsala universitet, Institutionen för medicinsk cellbiologi, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 237 |
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