School of Medicine

University of Washington School of Medicine
CVANS: The Structure Function

HUBIO 543
UW Restricted

CVANS MODULE

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Catecholamines as Neurotransmitters/Hormones

Actions of Catecholamines

Effects of slow infusion of catecholamines in humans

The data shown in this section were adapted from a classical publication on the effects of catecholamine infusion in human volunteers (Allwood et al., British Medical Bulletin 19: 132-136, 1963). In this publication catecholamines were infused in human volunteers for 15 min. The infusion rates for the three potent catecholamines were 10 micrograms (mcg) per min. Dopamine, which is a much less potent compound, was infused at a rate of 500 mcg/ min. Because each of these compounds has a very short half life, a steady state level was (presumably) reached in plasma within a few minutes and a steady state set of effects persisted for most of the 15 min of infusion.

There are some differences between the effects of catecholamines infused slowly in humans (as here) versus a large, rapid IV bolus in dogs (as in the virtual). The differences are due mainly to the size and duration of dosage, as well as the performance of cardiovascular reflexes in conscious humans versus those in an anesthetized dog (often vagotomized, or otherwise vagally compromised, etc). In humans, for example the dose of epinephrine was equivalent to about 0.14 mcg/kg/min. In the experimental dog the dose was 2 mcg/kg, injected as a bolus (much less than a minute). In spite of some differences in the responses, the same underlying pharmacological actions of EPI (activation of vascular alpha-1 and beta-2 receptors and activation of cardiac beta-1 adrenergic receptors) are present in both species.

Epinephrine

EPI is a potent agonist of both alpha and beta receptors. Thus it produces both vasodilation (mainly in skeletal muscle beds) and vasoconstriction (especially skin and viscera). The vasodilatory effects, mediated by beta-2 receptors are activated at low concentrations. At intermediate concentrations both beta-2 and alpha-1 effects on blood vessels are present. EPI exerts direct positive inotropic and chronotropic effects (beta-1), although the latter may be blunted or masked by the baroreceptor reflex. The result shown here is an overall slight decrease in peripheral resistance, an increase in pulse pressure with little or no change in mean blood pressure. Because mean blood pressure did not change, the positive chronotropic effect of epinephrine was also evident.

Norepinephrine

NE is an agonist of alpha receptors and beta-1 receptors. It produces intense vasoconstriction without any component of vasodilation. By its action on beta-1 receptors it exerts direct positive inotropic and chronotropic effects, the latter possibly masked by the baroreceptor reflex. The result is that NE increases peripheral vascular resistance, pulse pressure and mean arterial pressure. Because of the increase in mean arterial pressure, there is a reflex bradycardia.

Isproterenol

ISO is an agonist of beta receptors. It produces vasodilation (beta-2) without any component of vasoconstriction. By its action on beta-1 receptors it exerts direct positive inotropic and chronotropic effects. The result is that ISO decreases peripheral vascular resistance, pulse pressure and mean arterial pressure. Heart rate increases substantially because of direct effects of ISO and reflexly because of the decreased mean arterial pressure.

Dopamine

DA is an agonist of dopamine D1 receptors and a less potent agonist of beta-1 receptors. At high concentrations it may act as an agonist of alpha-1 receptors and may promote the release of NE from sympathetic nerve terminals. D1 receptors promote vasodilation in renal, mesenteric and coronary beds. The result is that DA decreases peripheral vascular resistance, increases pulse pressure and mean arterial pressure. The positive chronotropic effect of DA produces a small increase in heart rate as well.