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.

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The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac volume overload. Aortocaval shunt (ACS) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoproterenol dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index were evaluated in plasma and heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol, and the beta(1)/beta(2)-adrenoceptor ratio were estimated. Four weeks of cardiac volume overload resulted in a 55% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 3.9 +/- 0.1 mg/g in sham and ACS rats, respectively) and a 20% increase in protein contents (from 11.3 +/- 0.7 to 13.8 +/- 1.1 mg/100 mg ventricles in sham and ACS rats, respectively). Furthermore, NA and A concentrations and NA turn-over index were increased in ACS rats (14, 40 and 80% versus sham, respectively). A shift to the right of the responses in heart rate, left ventricular systolic pressure, +dP/dtmax and -dP/dtmax responses following increasing doses of isoproterenol was observed, without change in the dose inducing maximum effect. Total beta-adrenoceptor characteristics and beta(1)/beta(2) ratio were unchanged. However, beta(1)-adrenoceptor density increased in epicardium while decreasing in endocardium of left ventricle from ACS rats. Rightward shift at lower doses of isoproterenol-induced cardiac responses in volume-overloaded rats are not likely due to overall beta-adrenoceptor density changes.

The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac pressure-overload. Abdominal aortic constriction (AAC) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoprenaline dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index (DHPG /NE ratio) were evaluated in heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol and the beta (1)/beta (2)-adrenoceptor ratio were estimated. Four weeks of cardiac pressure overload resulted in a 70% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 4.2 +/- 0.3 mg/g in sham and AAC rats, respectively) and a 24% increase in protein contents (from 11.3 +/- 0.7 to 14.0 +/- 1.1 mg/100 mg ventricle in sham and AAC rats respectively). The ventricle NA content was similar in AAC and sham, while the ventricle A content and NA turn-over index were significantly increased in AAC rats (35 and 80% vs sham, respectively). Dose response of isoprenaline was significantly shifted to the right for all studied effects in AAC rats. However, maximal response (in relative values) was similar in AAC and sham rats only for heart rate but not for parameters depending on left ventricle contractile response. The beta-adrenoceptor density was significantly decreased in AAC by 30% without apparent affinity change and due to decreases in beta (1)-sites in septum and to beta (1)- and beta (2)-adrenoceptors in left ventricle endocardium. Decreases in isoprenaline-induced cardiac responses in AAC rats are associated with beta (1)-adrenoceptor density reduction and modification of beta (1)- and beta (2)-adrenoceptor ratio. These modifications are not the only reason for such dose response changes, at least for contractile response.