Differential cardiovascular and neuroendocrine effects of epinine and dopamine in conscious pigs before and after adrenoceptor blockade

Abstract

1 The effects of epinine or dopamine (both 1-10 tg kg-min-') on systemic haemodynamics and plasma concentrations of catecholamines and prolactin were studied in conscious pigs before and after combined non-selective a-and P-adrenoceptor blockade.2 The plasma concentrations of the two compounds did not differ from each other over the entire dose-range. 3 Epinine increased aortic blood flow (AoBF, 24 ± 6%), which was due to an increase in heart rate (HR) for doses less than 10 ,g kg-' min-'. At 10 fg kg-' min-', HR decreased slightly (10 ± 3%, as compared to the value obtained at 5 psg kg-' min-') and stroke volume increased up to 15% (P <0.05). Mean arterial pressure (MAP, 99 ± 3 mmHg at baseline) decreased dose-dependently (14 ± 2%, P <0.05) up to the infusion rate of 5 tLg kg-' min-, but increased by 4.0 ± 1.8 mmHg during infusion of 10 1tg kg' min-'. Systemic vascular resistance (SVR) decreased up to 23 ± 3% for doses less than 10 yg kg-I min', but did not change further during infusion of the highest dose. LVdP/dt,,,, increased during the two highest infusion rates up to 22 ± 6% (P <0.05). After the infusion was stopped there was an abrupt increase in HR (18 ± 4%, P<0.05) and a further decrease in SVR before all parameters returned to baseline. 4 Dopamine caused increases in AoBF (27 ± 3%) similar to epinine, the only difference being that HR continued to increase (32 ± 5%) and MAP (13 ± 3%) and SVR continued to decrease (31 ± 3%) over the entire dose-range. The increase in LVdP/dt,,,, at the highest dose (48 ± 4%, P <0.05) was more pronounced than with epinine. 5 Adrenoceptor blockade inhibited all epinine-induced changes, but did not affect the dopamineinduced changes in AoBF, SVR and MAP, but attenuated the increases in HR and LVdP/dtmax. 6 Noradrenaline (NA) and adrenaline (Ad) concentrations did not change during infusion of epinine or dopamine, but NA increased by 50% within 2.5 min after stopping the infusion of epinine. After adrenoceptor blockade NA and Ad concentrations did not change during infusion of dopamine, which contrasted with a decrease of 55 ± 5% (P<0.05) in NA during infusion of epinine. 7 Prolactin concentrations decreased gradually from 480 ± 40 pg ml-' to 270 ± 50 pg ml1' (P < 0.05) during infusion of epinine, but did not change significantly during dopamine infusion. 8 The differential effects of epinine and dopamine on MAP, SVR, plasma NA (before and after adrenoceptor blockade) and prolactin, leads us to conclude that in conscious pigs, epinine is a more potent a, P2 and D2-receptor agonist, but a weaker D,-receptor agonist than dopamine.

Systemic, pulmonary and coronary haemodynamic actions of the novel dopamine receptor agonist in awake pigs at rest and during treadmill exercise Z1046

“…D 2 ‐receptors are situated on sympathetic nerve endings (inhibition of noradrenaline release), in the zona glomerulosa cells of the adrenal cortex (inhibition of angiotensin II‐stimulated aldos‐terone release) and in sympathetic ganglia (inhibition of ganglionic transmission). Experimental and clinical evidence is accumulating that specific dopamine agonists may be of use in the treatment of hypertension and heart failure (Goldberg, 1972; Van Woerkens et al , 1991; 1992c; Rousseau et al , 1994). In particular, combined D 1 ‐/D 2 ‐receptor agonists could be of benefit in hypertension as they are likely to minimize barore‐flex‐mediated activation of the sympathetic nervous system.…”