title: Enhanced adenosine A(2B) mediated coronary response in reserpinised rat heart.
abstract: In this study, we investigated the effect of noradrenaline depletion on contractile recovery in rat isolated heart following myocardial ischaemia. Groups tested included control tissues and hearts from reserpinised rats. Reserpine 1 mg/kg s.c. was injected into rats 18 to 24 h prior to experiments. Hearts underwent 15 min global normothermic ischaemia followed by 30 min reperfusion. Functional data (end diastolic pressure (EDP), heart rate (HR), left ventricular developed pressure (LVDP), dP/dt(max), dP/dt(min)) showed that contractile function following ischaemia-reperfusion is unaffected by reserpinisation. However, pre- and post-ischaemic coronary flow rates (CFR) were increased by 16 to 38% in hearts from reserpinised rats versus control hearts. Pre-ischaemic CFRs in control hearts (11.17+/-0.67 ml/in(-1) x g tissue(-1), n=9) were significantly lower then CFRs derived from reserpinised rat hearts (14.57+/-0.72 ml/min(-1)/g tissue(-1), n=10). Post-ischaemic reactive hyperaemia was evident in all groups. CFRs in reserpinised hearts remained elevated when compared to pre-ischaemic values through reperfusion (P<0.05). Reserpine treatment did not significantly alter pre- or post-ischaemic adenosine efflux. The A(2B) adenosine receptor antagonist alloxazine (10 microM) attenuated pre- and post-ischaemic CFRs in both control and reserpinised hearts (P<0.05) without altering the hyperaemic response while the A(2A) adenosine receptor antagonist 8-(3-chlorostyryl) caffeine (1 microM) did not alter CFRs in both groups. The A(3) adenosine receptor antagonist MRS1191 (0.1 microM) increased CFR in control and reserpinised hearts (P<0.05). Catecholamine depletion with reserpinisation enhances the responsiveness of the coronary resistance vessels to endogenous adenosine through activation of the A(2B) adenosine receptor.
authors.affiliation: Heart Foundation Research Centre, School of Health Sciences, Griffith University, PMB50 Gold Coast Mail Centre, 9726, Queensland, Australia. r.rosemeyer@mailbox.gu.edu.au
authors.forename: Roselyn B
authors.initials: RB
authors.lastname: Rose'Meyer
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Harrison
authors.forename: John P
authors.initials: JP
authors.lastname: Headrick
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D005415:Flavins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D012110:Reserpine / Q000494:pharmacology*; D013997:Time Factors; D014439:Tyramine / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors; D005415:Flavins; D011687:Purines; D014665:Vasodilator Agents; C047235:N-(1-methyl-2-phenylethyl)adenosine; C008173:isoalloxazine; D012110:Reserpine; D000241:Adenosine; C030985:purine; D009638:Norepinephrine; D014439:Tyramine