In vivo demonstration of α-adrenoceptor-mediated positive inotropy in pithed rats:: evidence that noradrenaline does not stimulate myocardial α-adrenoceptors

1 This study examines whether positive inotropy via or-adrenoceptors could be observed in vivo in pithed rats. Cardiac contractility was measured as the maximum rate of rise of left ventricular pressure (dP/dt(max)). Heart rate and aortic blood pressure were also recorded. 2 The selective alpha(1)-adrenoceptor agonists, methoxamine, cirazoline, amidephrine and phenylephrine caused dose-related increases in dP/dt(max). This response was progressively reduced by increasing doses of the alpha(1)-adrenoceptor antagonist prazosin. However, since the concomitant increase in diastolic blood pressure (DBP) was also blocked, the changes in dP/dt(max) may have been a consequence of increased after load. 3 Adrenaline and noradrenaline also increased dP/dt(max), accompanied by presser responses. Propranolol (1 mg kg(-1)) antagonized the increase in dP/dt(max) in response to noradrenaline, suggesting beta-adrenoceptor involvement, but not that to adrenaline. The additional presence of prazosin (1 mg kg(-1)) further shifted the dose-response curves for both noradrenaline and adrenaline to the right. 4 Analysis of the increases in dP/dt(max) at predetermined increases in DBP by each agonist revealed three groups of regression lines. Adrenaline in the presence of propranolol and the four selective alpha(1)-adrenoceptor agonists occupied a common central position. Above this group were adrenaline and noradrenaline in the absence of antagonists; their additional effects on contractility were beta-adrenoceptor-mediated since the regression lines were lowered by propranolol. Clearly below the main group of agonists was noradrenaline in the presence of propranolol. 5 Thus, for a given increase in DBP, adrenaline (in the presence of beta-blockade) and the alpha(1)-adrenoceptor agonists exert an additional inotropic effect to noradrenaline (also in the presence of beta-blockade). This is concluded to be an alpha-adrenoceptor-mediated increase in cardiac contractility which is not shared by noradrenaline.