The highly basic peptide adipocytokine apelin-13 is the ligand for the G protein-coupled orphan receptor APJ (Tatemoto et al., 1998). The Apelin/APJ system is espressed in almost all tissues. On cardiovascular apparatus, apelin produces inotropic effects involving Na+/H+ and Na+/Ca2+ exchangers (Szokody et al., 2002) and vasodilatatory effects involving nitric oxide (NO) (Tatemoto et al., 2001). Simpkin et al. (2007) observed that in isolated rat hearts the addition of apelin during reperfusion attenuates ischaemia-reperfusion (I/R) injury. Since global I/R induces myocardial contracture, we wanted to see whether Apelin-induced vasodilation and myocardial protection can counteract the effect of contracture on coronary vascular resistance (CVR). Method. Thirty eight anaesthetized rats were killed by decapitation. The hearts were excised and perfused at constant flow with oxygenated Krebs-Henseleit buffer. Coronary perfusion and left ventricular pressure (LVP) were recorded. After stabilization, the hearts underwent 30 min of global ischaemia and 20 min of reperfusion. Apelin-13 was given at 0,5 mM concentration. Five groups of hearts were performed. In Group I (n = 7; control) the hearts underwent I/R only. In Group II (n=7) they received apelin before I/R for 20min. The other groups received apelin during reperfusion for the same duration. While Group III (n=6) received only apelin, the NOS inhibitor L-NNA and the guanylate-cyclase (GC) inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ) were added in Group IV (n=8) and V (n=6) respectively. Results. Data are give as means ± SEM. In Group I a 26±11% increase of CVR occurred in reperfusion. Apelin before ischaemia (Group II) caused a 23±7% increase of CVR during stabilization and 80±18% at the end of reperfusion. When apelin was given during reperfusion (Group III) CVR was similar as in Group I (34±7%) and did not change if NO-synthase and guanylil-cyclase were blocked by L-NNA (Group IV, 45±20%) and ODQ (Group V, 42±16%) respectively. During reperfusion end-diastolic LVP was increased 20±9 folds in Group I, 14±4 in Group II and 22±10 in Group IV. It is likely that apelin before ischaemia induces a vasoconstriction by the activation by Na+/H+ and Na+/Ca2+ exchangers not only in myocardium but also in coronary smooth muscle cells. During reperfusion myocardial contracture contributed to the further increase of CVR. Given after ischaemia apelin produced a vasodilatation that exceeded the effect of contracture. The absence of any effect of NO blockade suggests that apelin-induced vasodilatation may be mediated not only by NO but also by some other factors (e.g. hyperpolarizing factor).
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