Dopamine vascular effects

Cardiovascular effects of Infusion of norepinephrine, epinephrine, Isoproterenol, and dopamine in humans. Infusions were made intravenously during the time indicated by the broken lines. Heart rate is given in beats per minute, blood pressure in millimeters of mercury, and peripheral resistance in arterial blood pressure. (Reprinted with permission from Allwood MJ, Cobbald AF, and Ginsburg J. Peripheral vascular effects of noradrenaline, isopropyl-noradrenaline, and dopamine. Br Med Bull 19 132, 1963. Reproduced by permission of the Medical Department, The British Council. 

Age-dependent, receptor-mediated drug effects have been observed with dopamine. The effect of dopamine on blood flow (estimated by measuring the pulsatility index by ultrasonography) was assessed in the right renal, superior mesenteric, and middle cerebral arteries in sick premature infants (52). Renal blood flow increased during the dopamine infusion, but mesenteric and cerebral blood flow were not altered. In adults, dopamine does increase blood flow to the intestine, indicating that the lack of response in preterm neonates is related to the immaturity of the mesenteric vascular bed. 

Dobutamine, a synthetic catecholamine, is a - and 82-receptor agonist with some a -agonist effects (see Table 14—14). Unhke dopamine, dobutamine does not cause release of NE from nerve terminals. The overall hemodynamic effects of dobutamine are the result of its effects on adrenergic receptors and reflex-mediated actions. Its P2-receptor-mediated effects are greater than those of dopamine, and /82-receptor-mediated vasodilation will tend to offset some of the -receptor-mediated vasoconstriction. Thus the uet vascular effect is usually vasodilation. The positive inotropy is primarily a P -receptor-mediated effect. Cardiac -receptor stimulation by dobutamine causes an increase in contractility but generally no significant change in heart rate and may provide an explanation for the apparently more modest chronotropic actions of dobutamine compared with dopamine. 

FIGURE 10-2 Modified from Allwood MJ etal. Peripheral vascular effects of noradrenaline, isopropylnoradrenaline, and dopamine. BrMed Bull 19 132—136, 1963. By permission of Oxford University Press. 

Dopamine produces dose-dependent hemodynamic effects because of its relative affinity for cq-, /Jr, /J2-, and Dr (vascular dopaminergic) receptors. Positive inotropic effects mediated primarily by / -receptors become more prominent with doses of 2 to 5 mcg/kg/min. At doses between 5 to 10 mcg/kg/min, chronotropic and -mediated vasoconstricting effects become more prominent. Especially at higher doses, dopamine alters several parameters that increase myocardial oxygen demand and potentially decrease myocardial blood flow, worsening ischemia in some patients with coronary artery disease. 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Dopamine is an intermediate product in the biosynthesis of noradrenaline. Furthermore it is an active transmitter by itself in basal ganglia (caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence and some areas in the frontal cortex. It is functionally important, for example in the extra-pyramidal system and the central regulation of emesis. In the periphery specific dopamine receptors (Di-receptors) can be found in the upper gastrointestinal tract, in which a reduction of motility is mediated, and on vascular smooth muscle cells of splanchnic and renal arteries. Beside its effect on specific D-receptors, dopamine activates, at higher concentrations, a- and -adrenoceptors as well. Since its clinical profile is different from adrenaline and noradrenaline there are particular indications for dopamine, like situations of circulatory shock with a reduced kidney perfusion. Dopamine can dose-dependently induce nausea, vomiting, tachyarrhythmia and peripheral vasoconstriction. Dopamine can worsen cardiac ischaemia. 

The cardiovascular response to dopamine in humans depends on the concentration infused. Low rates of dopamine infusion can produce vasodilation in the renal, mesenteric, coronary, and intercerebral vascular beds with little effect on other blood vessels or on the heart. The vasodilation produced by dopamine is not antagonized by the p-adrenoceptor blocking agent propranolol but is antagonized by haloperidol and other dopamine receptor-blocking agents. 

Prompt intensive treatment with corticosteroids may be lifesaving when an excessive inflammatory reaction has resulted in septic shock. A massive infusion of corticosteroids can restore cardiac output and reverse hypotension by sensitizing the response of adrenoceptors in the heart and blood vessels to the stimulating action of catecholamines. This protective role of steroids may be due to a direct effect on vascular smooth muscle. The combination of glucocorticoids and dopamine therapy preserves renal blood flow during shock. 

Intravenous administration of dopamine promotes vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels, via activation of Di receptors. Activation of the Di receptors in the renal vasculature may also induce natriuresis. The renal effects of dopamine have been used clinically to improve perfusion to the kidney in situations of oliguria (abnormally low urinary output). The activation of presynaptic D2 receptors suppresses norepinephrine release, but it is unclear if this contributes to cardiovascular effects of dopamine. In addition, dopamine activates Bj receptors in the heart. At low doses, peripheral resistance may decrease. At higher rates of infusion, dopamine activates vascular a. receptors, leading to vasoconstriction, including in the renal vascular bed. Consequently, high rates of infusion of dopamine may mimic the actions of epinephrine. 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

Vascular smooth muscle tone is regulated by adrenoceptors consequently, catecholamines are important in controlling peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance, whereas 2 receptors promote smooth muscle relaxation. There are major differences in receptor types in the various vascular beds (Table 9-4). The skin vessels have predominantly receptors and constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels. Vessels in skeletal muscle may constrict or dilate depending on whether ffor 13 receptors are activated. Consequently, the overall effects of a sympathomimetic drug on blood vessels depend on the relative activities of that drug at and 8receptors and the anatomic sites of the vessels affected. In addition, Di receptors promote vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels. Activation of the Di receptors in the renal vasculature may play a major role in the natriuresis induced by pharmacologic administration of dopamine. 

The required properties of such an agent Included (1) selectivity for peripheral vascular dopaminergic receptors versus < -and 6-adrenerglc receptors which could mediate pressor and cardiac effects, (2) absence of central dopaminergic and emetic effects, and (3) potent oral renal vasodilator effects. Dopamine has been associated with diuresis and natriuresls. Possible mechanisms include a direct tubular effect on sodium transport, indirect effects produced by changes in total or regional renal blood flow, or effects resulting from a dopamine Induced decrease in aldosterone release from the adrenal (9). Since diuretics play a key role in antihypertensive therapy, the addition of a natriuretic/diuretic component to the renal vasodilator profile would be valuable and appeared to be feasible. 

Epinephrine [ep ee NEF rin] is one of five catecholamines—epinephrine, norepinephrine, dopamine, dobutamine, and isoproterenol—commonly used in therapy. The first three catecholamines occur naturally, the latter two are synthetic compounds (see Figure 6.7). Epinephrine is synthesized from tyrosine in the adrenal medulla and released, along with small quantities of norepinephrine, into the blood stream. Epinephrine interacts with both a and p receptors. At low doses, p effects (vasodilation) on the vascular system predominate, whereas at high doses, a effects (vasoconstrictor) are strongest. 

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