Mesenteric and renal vascular effects of diadenosine polyphosphates (APnA).
Diadenosine polyphosphates (APnA) are endogenous dinucleoside molecules consisting of two adenosine moieties linked via their 5'-ribose positions by a variable number of phosphate groups. APnA have been shown to be present in different cell types and to be released from platelets as well as co-released with catecholamines and ATP from bovine adrenal medulla. Candidate metabolites of APnA are ATP, ADP, AMP and adenosine. Vascular effects induced by APnA and their metabolites in several models have been reported to be mediated by A1- and A2-adenosine receptors as well as P2-purinoceptors. APnA have been demonstrated to differentially affect regional perfusion, to influence cardiac output and blood pressure as well as the reactivity of isolated blood vessels and vascular beds. Vascular effects of APnA vary with the number of phosphate groups linking the adenosine molecules. This review outlines the effects of APnA on mesenteric and renal circulation. The effects of the antagonists varying with the type of vascular bed and the heterogeneous and dynamic vascular effects of diadenosine polyphosphates indicate a regionally different distribution of P2X and of P2Y purinoceptors in resistance arteries from different vascular beds. Although APnA have vasoconstrictor effects on the local level, it was repeatedly confirmed that systemically applied APnA induce hypotensive effects. The vasoconstrictor effects of APnA in isolated vessels are most prominent under resting tone conditions. In vivo, the vasculature exhibits a vasotone which makes dilatory effects more likely. Information on effects of APnA in vivo is still limited despite the fact that these compounds already have been used in man.
Gabriëls
Gert
G
Medizinische Klinik und Poliklinik D, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Albert-Schweitzer-Strasse 33, Münster, Germany. gabrie@uni-muenster.de
Rahn
Karl Heinz
KH
Schlatter
Eberhard
E
Steinmetz
Martin
M
D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects*; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015226:Dinucleoside Phosphates; D018048:Receptors, Purinergic P2; D014665:Vasodilator Agents; C020733:diadenosine tetraphosphate