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INVITED REVIEW

Vasoconstrictor and vasodilator effects of adenosine in the kidney

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Submitted 6 February 2003 ; accepted in final form 30 March 2003

Adenosine is an ATP breakdown product that in most vessels causes vasodilatation and that contributes to the metabolic control of organ perfusion, i.e., to the match between oxygen demand and oxygen delivery. In the renal vasculature, in contrast, adenosine can produce vasoconstriction, a response that has been suggested to be an organ-specific version of metabolic control designed to restrict organ perfusion when transport work increases. However, the vasoconstriction elicited by an intravenous infusion of adenosine is only short lasting, being replaced within 1–2 min by vasodilatation. It appears that the steady-state response to the increase of plasma adenosine levels above normal resulting from the infusion is global renal vasorelaxation that is the result of A₂AR activation in most parts of the renal vasculature, including larger renal arteries, juxtamedullary afferent arterioles, efferent arterioles, and medullary vessels. A₂AR-mediated vasorelaxation is probably facilitated by endothelial receptors that cause the release of nitric oxide and other endothelial relaxing factors. In contrast, isolated perfused afferent arterioles of superficial and midcortical nephrons of rabbit and mouse, especially in their most distal segment at the entrance to the glomerulus, respond to adenosine with persistent vasoconstriction, indicating predominant or exclusive expression of A₁AR. A₁AR in afferent arterioles are selectively activated from the interstitial aspect of the vessel. This property can dissociate A₁AR activation from changes in vascular adenosine concentration, a characteristic that is ideally suited for the role of renal adenosine as a paracrine factor in the control of glomerular function.

adenosine receptors; vascular resistance; renal blood flow; endothelium

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