Intravenous Infusion Of Dopamine Research Articles

Blood flow redistribution by dopamine in the feline gastrointestinal tract.

The effect of intravenous infusion of dopamine (10 and 25 micrograms X kg-1 X min-1 consecutively) on visceral blood flow distribution was examined in anesthetized cats using the microsphere technique and electromagnetic flowmetry. Arterial blood pressure did not change in response to dopamine infusion, but blood flow through the superior mesenteric artery, and blood flow in the mucosa-submucosa of the gastric antrum and various gut segments increased significantly. During infusion of the high dose the increase was most marked in the mucosa-submucosa of the antrum (+355%) and distal colon (+371%). By contrast, blood flow decreased in the muscularis-serosa of the gut segments investigated, in the spleen, pancreas, and the hepatic arterial bed. The increase in blood flow through the superior mesenteric artery was blocked by the dopamine antagonist bulbocapnine (10 mg/kg i.v.). The results suggest that the receptors mediating the dopamine-induced vasodilation in the gastrointestinal tract are located in the resistance vessels of the mucosa-submucosa.

Aortic body chemoreceptor responses to dopamine, haloperidol, and pargyline.

Aortic chemoreceptor activity, from single- or few-fiber afferent nerve preparations, was measured in response to dopamine and a dopaminergic blocker, haloperidol, in 18 anesthetized cats. In six of these cats the effect of dopamine was assessed before and after inhibiting monoamine oxidase (MAO) by pargyline. Intravenous dopamine infusion (7-14 microgram X kg-1 X min-1) had a generally inhibitory effect on aortic chemoreceptor activity, but the magnitude of this effect varied with arterial partial pressure of O2 (Pao2) levels. The inhibitory effect of dopamine increased as Pao2 levels fell, and at severely hypoxic Pao2 levels (below 30 Torr) exogenous dopamine had no significant effect. The inhibitory effect of dopamine also increased during hyperoxic hypercapnia. Blockade of dopamine receptors in the aortic body by haloperidol-stimulated chemoreceptor activity significantly during hypoxia, suggesting an O2-dependent release of dopamine from the aortic body as Pao2 falls. Inhibition of MAO by pargyline had no significant effect on the control rate of activity at any level of Pao2 but augmented the inhibitory effect of exogenously administered dopamine. These data indicate that MAO is not significantly involved in the degradation of endogenous dopamine at the aortic receptor sites, but may participate in the degradation of exogenous dopamine.

Hemodynamic and natriuretic responses to intravenous infusion of dopamine in patients with essential hypertension.

In order to clarify the role of dopamine on the pathophysiology of essential hypertension, mean arterial pressure (MAP), heart rate (HR), urine volume (UV), urinary sodium excretion (UNaV), endogenous creatinine clearance (Ccr), fractional excretions of sodium (FENa), inorganic phosphorus (FEP) and potassium (FEK), plasma renin activity (PRA), plasma aldosterone concentration (PAC) and plasma noradrenaline concentration (PNA) were measured before and after intravenous infusion of dopamine (3 micrograms/kg/min, 60 min) in normotensive (NT) and essential hypertensive subjects (EHT). Following dopamine infusion, a significant decrease of MAP and an increase of HR were observed in EHT but not in NT. UV, UNaV, Ccr, FENa, FEP and FEK increased significantly in both NT and EHT, and changes in these except for Ccr were significantly greater in EHT than in NT. In EHT, following dopamine infusion, PNA was clearly elevated, but no remarkable change was found in PRA and PAC. A significantly positive correlation was found between delta UNaV and delta FENa or delta FEP, and between delta FENa and delta FEP, while no significant relation was observed between delta UNaV and delta Ccr, delta MAP or MAP before dopamine infusion. A significant inverse correlation between supine PRA before dopamine infusion and delta FENa or delta FEP and a positive correlation between age and delta FENa or delta FEP were also observed in these patients. The changes in UNaV positively correlated with delta FENa and delta FEP in both low renin (group L) and normal renin EHT (group N) and with delta Ccr i group N but not in group L. The mean values of delta FENa, delta FEP and delta FEK were significantly higher in group L as compared with those in age-matched group N. These results suggest that, since the enhanced response to infused dopamine may reflect reduced dopaminergic activity, attenuation of renal dopaminergic activity might exist and be involved through a distribution of water-sodium metabolism, at least in part, in the pathophysiological mechanism in EHT, particularly in group L.

Effects of vagotomy and glossopharyngectomy on respiratory response to dopamine‐agonists

In normal rats lightly anesthetized with halothane apomorphine increased both resting and CO2-dependent minute ventilation (VM) by stimulating respiratory frequency (RF) whereas tidal volume (VT) was slightly decreased. Acute bilateral glossopharyngectomy, which impaired carotid body function, did not change the apomorphine effects in contrast to bilateral vagotomy, which abolished the RF response of the drug, but now increased VT. Intravenous infusion of dopamine increased VM by elevating RF, and this effect was only slightly blunted by bilateral glossopharyngectomy but nearly abolished by vagotomy and totally eliminated by the combined procedures. The respiratory response to dopamine was depressed in rats with chronically destroyed central catecholaminergic neurons. These findings indicate that there may be two different dopaminergic stimulatory mechanisms that modulate RF-one peripheral and one central-and both depend upon afferent vagal activity. With impaired vagal function, however, two other dopaminergic stimulatory mechanisms effecting VT are evident-one central, and one peripheral which involves the carotid body.

Pharmacologic antagonism of beta adrenergic blockade in dogs. II. Hemodynamic effects of simultaneous intravenous infusion of isoproterenol and dopamine during chronic propranolol administration: Spotnitz HM, et al, J Thorac Cardiovasc Surg79:103–108, (Jan) 1980

Pharmacologic antagonism of beta adrenergic blockade in dogs. II. Hemodynamic effects of simultaneous intravenous infusion of isoproterenol and dopamine during chronic propranolol administration: Spotnitz HM, et al, J Thorac Cardiovasc Surg79:103–108, (Jan) 1980

Effects of dopamine on chemoreflexes in breathing.

The effects of intravenous infusion of dopamine (20 microgram.min) on the steady-state ventilatory and carotid chemoreceptor responses to successive levels of isocapnic hypoxia and hyperoxic hypercapnia were investigated in cats anesthetized with alpha-chloralose. Dopamine infusion was followed by a maximal decrease in ventilation in about 20 s. Thereafter, the effect diminished and stabilized. Termination of dopamine infusion was promptly followed by an increase in ventilation. These ventilatory responses were smaller than the corresponding carotid chemoreceptor responses. The steady-state effect of dopamine infusion was to diminish ventilation at all levels of arterial O2 tension, the decrease being greater during hypoxia than that during hyperoxia. Bilateral section of the carotid sinus nerves significantly diminished but did not abolish the inhibitory effect of dopamine on ventilation during hyperoxia. Thus the ventilatory depression due to dopamine infusion is not entirely due to its effect on the carotid chemoreceptors. Dopamine decreased ventilatory responses to successive levels of hypercapnia by the same magnitude without changing the slope of the response curves. The steady-state relationship between chemoreceptor activity and ventilation shows that the ventilatory equivalent for carotid chemoreceptor activity is increased during dopamine infusion because of its greater inhibitory effect on carotid chemoreceptor activity than on ventilation with the decrease of arterial O2 tension.

Effect of dopamine infusion on serum prolactin concentration in normal and hyperprolactinaemic subjects.

The serum prolactin response to intravenous dopamine infusion (5 micrograms . kg-1 . min-1) was measured in twenty-one healthy subjects, in seven hyperprolactinaemic patients without evidence of a pituitary tumour, and in twenty-one patients with prolactinomas. Mean serum prolactin values were significantly suppressed in all three groups, without any significant difference between the degree of suppression. A decrease of serum prolactin to below 50% of basal values occurred in fifteen healthy subjects, in four patients without evidence of pituitary tumour, and in fourteen patients with prolactinomas. These findings demonstrate that most human prolactin-secreting pituitary adenomas are normally suppressible by exogenously administered dopamine and that dopamine infusion is not able to distinguish between tumorous and non-tumorous hyperprolactinaemia. Since intravenously infused dopamine is believed to inhibit prolactin secretion by acting at pituitary level, it is suggested that a normal functioning of pituitary dopamine receptors is maintained in most human prolactinomas.

Parathyroid hormone response to dopamine in cattle.

The effects of dopaminergic agonists on plasma levels of parathyroid hormone (PTH) have been studied in cattle. PTH increased within minutes in a dose-dependent manner during intravenous infusions of dopamine (DA) or epinine. Bromocriptine, in amounts that lowered plasma prolactin, inconsistently elevated PTH. Pimozide suppressed PTH responses to DA, whereas propranolol, phentolamine, phenylephrine, and atropine were ineffective. Plasma calcium and magnesium remained unaltered during DA and epinine infusions. Therefore DA appears to stimulate PTH secretion directly. After prolonged DA infusions, the secretion of PTH became resistant to both the administration of DA and isoproterenol, whereas the parathyroid glands remained responsive to a hypocalcemia. On the other hand, calcium suppressed PTH responses to DA. The results suggest that DA, beta-adrenergic agonists, and low calcium stimulate PTH secretion by separate but closely related mechanisms. Based on biochemical and histochemical observations on DA occurring in high amounts in bovine parathyroid glands, it is conceivable that this amine might stimulate PTH secretion at the level of the gland.

Interaction of dopamine and haloperidol with O2 and CO2 chemoreception in carotid body.

Effects of dopamine and of a dopaminergic blocker, haloperidol, on the responses of carotid body chemoreceptors to hypoxia and hypercapnia were investigated in 16 anesthetized cats. Intravenous infusion of dopamine (10-20 micrograms.min-1) decreased carotid body chemoreceptor responses to hypoxia and hypercapnia. The effect was greater at higher levels of arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) stimulus. Thus, the magnitude of the dopamine effect depended on the degree of both PO2- and PCO2-mediated excitation of the receptors. Haloperidol potentiated responses to both hypoxia and hypercapnia but apparently did not stimulate the receptors in the absence of these stimuli. Potentiation by haloperidol and inhibition by dopamine of excitatory effects due to PaO2 decrease and PaCO2 increase are complementary. The data suggest that chemoreception of dopamine, O2, and CO2 converge at some site in the carotid body. Persistence of hypoxic and hypercapnic responses, following dopamine-blocking doses of haloperidol, does not support the theory that regulation of dopamine release is responsible for O2 and CO2 chemoreception in carotid body of the cat.

Dopamine-induced diuresis in the cat without changes in renal hemodynamics.

The effects of intravenous (i.v.) and intraarterial (i.a.) injection and infusion of dopamine (DA) on renal hemodynamics, regional sympathetic activity and kidney function were investigated in anaesthetized cats. In response to the i.v. bolus injection of DA (25 microgram/kg), mean arterial blood pressure (MABP) was increased by 19.7%, renal blood flow (RBF) by 16.6%, and regional sympathetic discharges were inhibited. The principal effect of i.a. bolus injection of DA into the renal artery was vasoconstriction. Vasodilation was observed neither after lower doses of DA nor after pretreatment with phenoxybenzamine. During continuous i.v. infusion of 10 microgram DA kg-1 min-1 MABP, RBF, renal sympathetic discharges and glomerular filtration rate (GFR) did not change, whereas urine volume was increased by 120.5%, sodium excretion by 99.7%, chloride excretion by 143.2%, and potassium excretion by 31.9%. Urine osmolality was decreased and osmolal clearance increased. Raising the DA dose to 25 microgram kg-1 min-1 resulted in a fall of GFR, but the diuretic response was not significantly different from that of the low dose. Bulbocapnine (6 mg/kg i.v.) antagonized the DA-induced diuresis. In conclusion, the diuretic effect of DA in the cat is not dependent on a change in RBF, GFR or renal sympathetic activity. This suggests that a tubular site of action is primarily responsible for DA diuresis.

Pharmacologic antagonism of beta adrenergic blockade in dogs: II. Hemodynamic effects of simultaneous intravenous infusion of isoproterenol and dopamine during chronic propranolol administration

Chronic beta adrenergic blockade was induced in eight dogs with 240 to 360 mg of oral propranolol dailty for 2 to 6 weeks. Beta blockade was confirmed by a minimal heart rate response to isoproterenol, 0.06 micrograms/kg/min, in a pentobarbital-anesthetized, open-chest preparation. Subsequent to confirmation of beta blockade, hemodynamic effects of isoproterenol and dopamine were examined individually and in combination. A desirable balance of arterial pressure and cardiac output was achieved by combining isoproterenol, 0.2 to 2.0 micrograms/kg/min, with dopamine, 5 to 20 micrograms/kg/min. This combination increased mean arterial pressure (109 +/- 9 versus 81 +/- 7), cardiac output (4.3 +/- .5 versus 2.8 +/- .3 L/min) and heart rate 156 +/- 4 versus 120 +/- 7) (p less than 0.05). The hemodynamic effects of combined isoproterenol-dopamine were superior to the effects of either drug alone and suggest a method for effective circulatory support of man during chronic beta adrenergic blockade.

Clonidine overdose: A review

The pharmacology and pharmacokinetics of clonidine and the symptoms and treatment of acute clinidine overdosage are reviewed. Clonidine, a relatively safe and effective antihypertensive agent when used at therapeutic dosages, reduces blood pressure through a centrally mediated reduction in vasomotor tone. The primary symptoms of clonidine overdosage are central nervous system depression, bradycardia, hypotension, miosis, hypotonia, respiratory depression and possibly seizures. Gastric lavage followed by administration of activated charcoal is used to decrease absorption following acute oral ingestion. Intravenous fluid therapy and dopamine infusion are recommended for severe hypotension, and atropine sulfate is used to manage persistent bradycardia. Treatment of hypotension with alpha-adrenergic blocking agents (e.g., tolazoline) is not recommended unless patients fail to respond to dopamine infusion and administration of i.v. fluids.

Gastrointestinal propulsion and mixing in the rat during infusion of dopamine.

The influence of continuous intravenous infusion of dopamine on gastric evacuation, small bowel propulsion and mixing was studied in the rat. The study revealed no influence of dopamine infusion on gastrointestinal transport mechanisms.

The portal hypertensive effect of dopamine

Intravenous infusions of either dopamine, vasopressin, or simultaneous dopamine and vasopressin were administered to normal adult mongrel dogs, and the effect on systemic and portal hemodynamics monitored. Dopamine increased superior mesenteric artery blood flow and portal venous pressure. Because of this portal hypertensive effect, dopamine should not be given to patients with cirrhosis and portal hypertension. Dopamine administered with vasopressin failed to protect against a reduction in cardiac output, and completely reversed the portal hypotensive effect of vasopressin. Isoproterenol remains the drug of choice for offsetting the adverse hemodynamic effects of vasopressin administration.

Effects of dopamine on whole kidney function and proximal transtubular volume fluxes in the rat.

The renal effects of dopamine were studied using clearance and micropuncture techniques in rats. Intravenous infusion of dopamine (4.7 - 10(-6) mol - kg-1 - h-1) increased glomerular filtration rate and renal blood flow. Renal blood flow was measured by an electromagnetic flowmeter. The increase in filtered fluid and sodium was nearly completely matched by increased tubular reabsorption. Thus, only a small rise in urine flow and in urinary sodium excretion was observed. The micropuncture experiments using the split oil droplet method of Gertz demonstrated a stimulation of the transepithelial fluid transfer after injection of dopamine (10(-4) M) into the proximal tubular lumen. This effect was abolished by simultaneous injection of propranolol (10(-3) M) which, by its own, did not affect transtubular volume fluxes. It is concluded that dopamine, by stimulation of beta-adrenoceptors, may increase reabsorptive capacity of the proximal tubular epithelium independent of changes in renal hemodynamics.

Blood pressure responses to noradrenaline and dopamine infusions in Parkinson's disease and the Shy‐Drager syndrome.

Studies of pulse rate and blood pressure responses to graded intravenous infusions of noradrenaline and dopamine were performed on five patients with Parkinson's disease, five with the Shy-Drager syndrome and seven healthy subject. Cardiovascular reflex responses to standing and to the Valsalva manoeuvre were found to be preserved in all patients with Parkinson's disease but to be grossly defective or absent in all with the Shy-Drager syndrome. Each subject received separate intravenous infusions of L-noradrenaline and dopamine, delivered at increasing rates, until a 30% rise in systolic blood pressure was achieved. Heart rate decreased during pressor responses to noradrenaline in control subjects and patients with Parkinson's disease, but increased in those with the Shy-Drager syndrome. Heart rate increased during pressor responses to dopamine in all subjects. Compared to control subjects supersensitivity to noradrenaline was observed both in patients with Parkinson's disease and, to a greater extent, in those with the Shy-Drager syndrome. Subsensitivity to dopamine was observed in patients with Parkinson's disease, but supersensitivity in those with the Shy-Drager syndrome.

Effects of Dopamine on Kidney Function and on the Adenyl Cyclase Phosphodiesterase System in Man

Clearance studies were made to determine the influence of intravenous infusions of dopamine (between 2.5 and 3.5 mug.kg.-1min.-1) on renal function and on the adenyl cyclase phosphodiesterase system in eleven patients with chronic renal disease. Glomerular filtration rate (+ 19%), effective renal plasma flow )+ 29%), sodium (+ 199%) and potassium (+ 40%) clearances were significantly increased. These effects were associated with a stimulation of the adenyl cyclase phosphodiesterase system demonstrated by an increase of cyclic adenosine 3'5'-monophosphate in plasma and urine. The results suggest that dopamine probably affects renal function by activating the adenyl cyclase phosphodiesterase system.

CIRCULATING LEVELS OF CORTICOTROPHIN AND CORTISOL AFTER INFUSIONS OF L‐DOPA, DOPAMINE AND NORADRENALINE, IN MAN

Intravenous infusions of noradrenaline and dopamine in normal saline, and L-dopa in sodium lactate, were given to seven patients with Parkinsonism, and to five healthy volunteers. Infusions of saline and lactate were given, in a similar manner, to six additional healthy volunteers, who formed a control group. Dopamine and noradrenaline were each given in gradually increasing doses, for periods of 4 min, until a 30% increase in systolic blood pressure had occurred. L-Dopa (320 mg) was given a constant rate of infusion over 80 min. Plasma fluorogenic corticosteroids (cortisol) increased with dopamine , and decreased with noradrenaline. These changes were significantly different from the control group in the case of noradrenaline only. ACTH values changed in a similar manner. L-Dopa produced a consistent rise in both ACTH and cortisol that was significantly different from control subjects. The implications of these observations are discussed.

Effect of dopamine and calcium on lipolysis and myocardial ischemic injury following acute coronary occlusion in the dog.

Ischemic myocardial injury was quantified as the sum of S-T segment elevations in epicardial electrocardiogram recordings (ΣS-T) following acute coronary artery occlusions in 17 dogs. ΣS-T rose from 3 ± 1 mv to 26 ± 4 mv ( P < 0.001) following occlusion. Myocardial contractility was similarly stimulated by intravenous infusions of dopamine or calcium. At reocclusions of the coronary artery, ΣS-T increased to 73 ± 12 mv ( P < 0.001) with dopamine and to 41 ± 7 mv ( P < 0.001) with calcium; the difference was statistically significant ( P < 0.005). Arterial concentrations of free fattv acids (FFA a ) were raised from 248 ± 33 µEq/liter to 888 ± 161 µEq/liter ( P < 0.005) with dopamine, but administration of calcium did not influence FFA a . After inhibition of lipolysis with β-pyridyl carbinol, no difference in ΣS-T or FFA a was observed; the mean values were 31 ± 4 mv for ΣS-T and 144 ± 13 µEq/liter for FFA a . Myocardial lipolysis was suggested in three experiments in which β-pyridyl carbinol reduced ΣS-T with dopamine, although FFA a remained unchanged. These measurements suggest that dopamine-induced lipolysis contributes significantly to the enlargement of ischemic injury in the myocardium following acute coronary artery occlusion, probably due to the metabolic stimulation of myocardial oxygen requirements. Test doses of dopamine given to seven patients raised FFA a by 225 ± 87 µEq/liter ( P < 0.03).

Redistribution of renal intracortical blood flow during dopamine infusion in dogs.

We determined the effect of intravenous and renal intra-arterial infusion of dopamine on the distribution of intracortical blood flow in kidneys of anesthetized dogs. Total renal and renal intracortical blood flows in dogs receiving dopamine intravenously were quantified by the radioactive microsphere technique with reference sampling. In dogs receiving dopamine by renal intra-arterial infusion, total renal and renal intracortical blood flows were determined from radioactive microsphere and electromagnetic flowmeter data. Tissue perfusion rates for the total kidney, the renal cortex, the renal outer cortex, and the renal inner cortex increased following either intravenous or direct renal intra-arterial infusion of dopamine. Dopamine infusion by either method caused a relative redistribution of renal blood flow from the outer twothirds to the inner one-third of the renal cortex. During direct dopamine infusion into the renal artery, no significant changes in renal hemodynamics occurred in the contralateral kidney. No changes in arterial blood pressure occurred during dopamine infusion by either method. These observations imply that the change in the fractional distribution of renal intracortical blood flow following dopamine infusion is not dependent on a systemic mode of action. This pattern of flow redistribution suggests that the intrarenal dopamine-specific receptor may be in higher number in the inner cortex or that the redistribution of cortical flow after dopamine infusion may reflect differing initial physiological states of the inner and outer cortical receptors for dopamine.