Enhanced adenosine A2B mediated coronary response in reserpinised rat heart.
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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/dtmax, dP/dtmin) 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/inm1.g tissuem1, n=9) were significantly lower then CFRs derived from reserpinised rat hearts (14.57-0.72 ml/minm1/g tissuem1, 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 A2B adenosine receptor antagonist alloxazine (10 wM) attenuated pre- and post-ischaemic CFRs in both control and reserpinised hearts (P<0.05) without altering the hyperaemic response while the A2A adenosine receptor antagonist 8-(3-chlorostyryl) caffeine (1 wM) did not alter CFRs in both groups. The A3 adenosine receptor antagonist MRS1191 (0.1 wM) 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 A2B adenosine receptor.
Naunyn-Schmiedeberg's Archives of Pharmacology