1 The aim of this study was to investigate whether histamine H 3 -receptor agonists could inhibit the eects of cardiac sympathetic nerve stimulation in the dog. 2 Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1 ± 4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-a-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP). 3 Cardiac sympathetic stimulation induced a noradrenaline release into the coronary sinus along with a tachycardia and an increase in left ventricular pressure and contractility without changes in mean arterial pressure. 4 Functional H 3 -receptors are present on sympathetic nerve endings in the dog heart. Their stimulation by R-a-methyl-histamine or BP 2.94 can inhibit noradrenaline release by the heart and its associated haemodynamic eects.

Kinin B1‐receptors are induced by various inflammatory stimuli. Since myocardial ischaemia‐reperfusion results in inflammation, we questioned whether it could induce B1‐receptor‐dependent responses to des‐Arg9‐bradykinin (DBK). Thirty‐six rabbits were submitted either to a 30 min coronary occlusion followed by a 3 h reperfusion or to a sham operation. The response to DBK was then tested in vivo on mean arterial pressure (MAP) and in vitro on isolated hearts and arterial rings. DBK induced a dose‐dependent decrease in MAP in the ischaemia‐reperfusion group (DBK, 10 μg kg−1, intra‐arterial: ‐12 ± 2 vs. ‐5 ± 2 mmHg in the sham group, P < 0.02), which was significantly antagonised by [Leu8]‐des‐Arg9‐bradykinin (LBK), a B1‐receptor antagonist. Following ischaemia‐reperfusion, isolated hearts responded to DBK by a decrease in coronary perfusion pressure greater than that of the sham group. DBK dose‐dependently decreased the isometric force of isolated carotid rings (DBK, 10−5m: ‐9 ± 2 vs. ‐1 ± 2 % in the sham group, P < 0.02) and mesenteric arteries (DBK, 10−6m: ‐38 ± 7 %vs. ‐3 ± 2 % in the sham group, P < 0.001). The vascular effects of DBK seen after ischaemia‐reperfusion were significantly antagonised by LBK. The presence of B1‐receptors in ischaemia‐reperfusion animals was confirmed by immunolocalisation and Western blot analysis. This study demonstrates that myocardial ischaemia‐reperfusion induces a global induction of functional kinin B1‐receptors in the endothelium.

1. We have tested the effects of 2 month oral treatment with the KATP opener, nitric oxide (NO) donor and anti-oxidant molecule nicorandil (0.1 mg/kg per day) on major physiological parameters and heart function of 4-, 12- and 24-month-old rats. 2. Several methods were used: (i) measurement of blood pressure using a non-invasive tail-cuff method; (ii) perfusion of isolated heart; (iii) lactate dehydrogenase (LDH) dosage; and (iv) measurement of monophasic action potential of rat isolated hearts. 3. Blood pressure and ventricular action potential duration regularly increase with age in control animals, whereas nicorandil restores these parameters in aged animals to levels present in young adult animals. Moreover, following ischaemia, nicorandil treatment improved isolated heart survival rate (100 vs. 50% for nicorandil-treated rats and controls, respectively), heart work and left ventricular developed pressure, whereas it decreased cardiac cell damage (LDH release) and perfusion pressure. 4. This condition of chronic oral nicorandil treatment presents a strong potential in the improvement of cardiac function in normal and pathological ageing.

1 Endotoxin is known to confer a delayed protection against myocardial infarction. Lipopolysaccharide (LPS) treatment also induces the de novo synthesis of kinin B 1 -receptors that are not present in normal conditions. The aim of this study was to evaluate whether LPS-induced B 1 -receptors are implicated in the reduction of infarct size brought about by LPS. 2 Rabbits were submitted to a 30-min coronary artery occlusion and 3-h reperfusion sequence. Six groups were studied: pretreated or not (control animals) with LPS (5 mg 3 The presence of B 1 -receptors in LPS-pretreated animals was con®rmed by a decrease in mean arterial pressure in response to B 1 stimulation. LPS-pretreatment signi®cantly reduced infarct size (6.4+1.7%, of area at risk vs 24.1+2.5% in control animals, P50.05). This protection was not modi®ed by B 1 -receptor antagonism (7.4+2.2%, NS) or stimulation (5.2+1.2%, NS). Neither antagonist nor agonist modi®ed infarct size in control animals. 4 In conclusion, these data suggest that LPS-induced myocardial protection in the rabbit is not related to concomitant de novo B 1 -receptor induction.