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Biomedical subjects

M B Murphy

Publications and source records attributed to M B Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1990

Dopamine, its receptors, and atrial natriuretic peptide.

Similarities in some of the physiological effects of dopamine (DA) and atrial natriuretic peptide (ANP) have stimulated suggestions that each may contribute to the actions of the other. While there have been many studies of possible interactions, use of poorly selective receptor antagonists, inappropriate doses, different animal species and various forms of ANP has led to confusing and conflicting results. Our review of the data concludes that it is unlikely that either dopamine generation or release, or DA receptor activation (with the possible exception of its involvement in the rat), are essential to the expression of the effects of ANP. DA actions do not depend on the release of ANP while there are no studies of DA activating ANP receptors.

Animals↗
PubMed1990

Role of endogenous dopamine in the natriuresis accompanying various sodium challenges.

The contribution of endogenous dopamine (DA) to the natriuresis accompanying various sodium challenges is reviewed. Data are presented suggesting that DA participates in the control of sodium excretion produced by a normal sodium diet, increments in sodium consumption, and an acute infusion of isoosmotic saline. In contrast, the natriuresis accompanying a high sodium diet in the dog and extracellular fluid volume expansion with hypoosmotic saline or a very large volume of isoosmotic saline is independent of DA activity. Thus, the evidence suggests that DA contributes to the natriuresis produced by some, but not all, forms of sodium loading.

Animals↗
PubMed1990

Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.

The renal and hemodynamic effects of intravenously administered fenoldopam mesylate, a novel dopamine-1 receptor agonist, were compared with those of sodium nitroprusside in 28 patients (18 male; 26 black, two white; average age, 49 +/- 3 years) with an average blood pressure of 219/137 mm Hg, most of whom presented with acute target organ damage. Fenoldopam and nitroprusside lowered blood pressure safely to an average pressure of 176/105 mm Hg; highly significant dose-response relations were found for the 13 patients receiving fenoldopam and the 15 receiving nitroprusside. Volume and sodium, potassium, and creatinine concentrations were measured in freely voided urine specimens both before and during intravenous therapy. In the fenoldopam-treated patients, there were significant increases in urinary flow (92 +/- 21 to 168 +/- 37 ml/hr, p less than 0.003), sodium excretion (227 +/- 73 to 335 +/- 90 mu eq/min, p less than 0.001), and creatinine clearance (70 +/- 11 to 93 +/- 13 ml/hr, p less than 0.003). In the nitroprusside-treated group, however, all these parameters decreased, but not significantly. For direct comparison of the two agents, the increments in urinary flow rate (+76 +/- 20 vs. -16 +/- 15 ml/hr, fenoldopam vs. nitroprusside), sodium excretion (+109 +/- 28 vs. -39 +/- 28 mu eq/min), and creatinine clearance (+23 +/- 6 vs. -11 +/- 7 ml/min) were significantly greater (p less than 0.001 for each) in the fenoldopam-treated group. Significant differences were also obtained when these parameters were calculated as percentage increase over baseline. Fenoldopam and nitroprusside are effective therapies for severe, accelerated, or malignant hypertension, but fenoldopam had additional salutary renal effects in these patients.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Dopamine and dopamine receptor agonists in cardiovascular therapy.

Dopamine (DA)--previously regarded simply as the precursor of norepinephrine--is now known to have its own unique effects on cardiovascular regulation which are mediated, in part, by activating specific DA receptors. DA has long been used in the treatment of shock and heart failure. In recent years it has been used at low infusion rates for its renal effects, in combination with other more specific inotropic or pressor agents. Lack of oral bioavailability has limited its use in long-term therapy, however; levodopa and dopa conjugates which are orally absorbed and metabolized to the active form are under investigation. The novel DA1 receptor agonist fenoldopam is claiming a role in the management of hypertension, heart failure, and the preservation of renal function. DA2 receptor agonists are also being evaluated as potential antihypertensive agents.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Clinical use of dopamine receptor agonists.

The development of novel DA receptor agonists, with various receptor selectivities, has confirmed the therapeutic utility of modulationing the peripheral dopaminergic system as Goldberg proposed 30 years ago. In addition to the acute therapy of heart failure, circulatory shock, and renal dysfunction, for which low dose DA has been standard therapy for many years, there is substantial evidence that DA receptor modulation will make a significant contribution to the chronic therapy of hypertension and congestive heart failure. However, development of drugs with adequate oral bioavailability remains a priority if we are to exploit fully these therapeutic possibilities.

Cardiovascular Diseases↗
PubMed1990

Equivalent antihypertensive effects of combination therapy using diuretic + calcium antagonist compared with diuretic + ACE inhibitor.

To test the hypothesis that the combination of a calcium antagonist and diuretic is less effective in lowering BP than the combination of ACE inhibitor plus diuretic, we compared two groups of patients. The first was a group of 157 consecutive patients (32% male, 90% black, aged 57 +/- 1 years) in whom the only change in therapy was the addition or deletion of either a calcium antagonist or diuretic. Each patient served as his/her own control, with a follow-up time of 41 +/- 4 days. The BP responses of this group were compared with those of another group of 170 consecutive patients (33% male, 85% black, aged 55 +/- 1 years), who had had the addition or deletion of an ACE inhibitor or diuretic some 32 +/- 2 days previously. As there were no statistically significant differences either between drugs within the classes or between the addition or deletion of a drug, the BP results were pooled. Combination therapy with calcium antagonist + diuretic was associated with a 13.4 +/- 1.7/5.4 +/- 0.9 mmHg drop in supine BP; the ACE inhibitor + diuretic combination lowered supine BP by 12.3 +/- 1.6/8.0 +/- 0.9 mmHg compared with monotherapy (all P less than 0.001 by paired t-test). The effects on standing BP were similar: calcium antagonist + diuretic, 13.2 +/- 1.9/5.6 +/- 0.9 mmHg; and ACE inhibitor + diuretic, 12.3 +/- 1.5/7.0 +/- 0.9 mmHg (all P less than 0.001). There were no significant differences in BP responses between the calcium antagonist + diuretic and ACE inhibitor + diuretic combinations. These data indicate that, regardless of the order of addition or subtraction, the combination of calcium antagonist + diuretic was more effective in lowering BP than either agent used alone, and that the combination of calcium antagonist + diuretic was as effective as the ACE inhibitor + diuretic combination.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Potentiation by dopexamine of the cardiac responses to circulating and neuronally released norepinephrine: a possible mechanism for the therapeutic effects of the drug.

Dopexamine is a new dopamine receptor agonist which also inhibits the uptake of norepinephrine (NE) into sympathetic nerves. Dopexamine was infused intravenously (i.v.) in anesthetized dogs at a rate used for treatment of congestive heart failure (4 micrograms/kg/min) before and during i.v. infusions of NE (0.26 +/- 0.06 and 0.57 +/- 0.12 micrograms/kg/min) and before and during cardioaccelerator nerve stimulation (0.25 and 0.50 Hz). Increments in cardiac contractile force produced by both infusion rates of NE were greater during dopexamine infusion; increases in heart rate (HR) and mean arterial pressure (MAP) produced by the higher infusion of NE also were increased by dopexamine. During cardioaccelerator nerve stimulation, 0.25 and 0.50 Hz, the increments in HR were significantly greater during dopexamine infusion; MAP also increased significantly during cardioaccelerator nerve stimulation (0.50 Hz) in the presence of dopexamine. Plasma NE concentration was significantly elevated during infusion of dopexamine. However, dopexamine did not enhance the elevated plasma NE concentration produced by NE infusions. This study demonstrates that infusion of dopexamine potentiates the cardiovascular effects resulting from neuronally released and exogenously infused NE.

Adrenergic Agonists↗
PubMed1989

Effects of dopamine receptor activation on the level of cyclic AMP in the trabecular meshwork.

We examined the effects of dopamine and of a selective DA1 agonist, fenoldopam, on the levels of cyclic AMP in the trabecular meshwork, freshly excised from porcine and canine eyes. As measured by radioimmunoassay, fenoldopam at a concentration of 10(-5) M caused a 4-fold increase in the cyclic AMP content, from a basal level of 24.4 +/- 1.9 to 101.8 +/- 6.3 pmol/mg protein, of the trabecular meshwork samples from porcine eyes. In tissue samples from canine eyes, fenoldopam at a concentration of 10(-4) M increased the endogenous cyclic AMP level from a basal value of 26.0 +/- 4.6 to 64.2 +/- 5.7 pmol/mg protein. Dopamine, although less potent, produced a similar response. Preincubation with a DA1 receptor antagonist, SCH 23390, inhibited the increase in cyclic AMP levels by 90%. Such inhibition did not occur with the alpha- and beta-receptor antagonists phenoxybenzamine and propranolol, respectively. This investigation demonstrates that adenylate cyclase-coupled DA1 receptors are present in porcine and canine trabecular meshwork tissue.

Animals↗
PubMed1989

Improved safety of glucagon testing for pheochromocytoma by prior alpha-receptor blockade. A controlled trial in a patient with a mixed ganglioneuroma/pheochromocytoma.

The glucagon stimulation test has been superseded in recent years by the clonidine suppression test because it can provoke dangerous increases in blood pressure in patients with pheochromocytomas. We describe the first patient in whom a pheochromocytoma was diagnosed by a glucagon test, after which the blood pressure (but not the plasma catecholamine) response to a second injection of glucagon was blocked by pretreatment with phenoxybenzamine. After the tumor (which contained both pheochromocytoma and ganglioneuroma tissue) was removed, a third glucagon test result was negative. This experience suggests that patients with normal plasma catecholamine levels who are suspected of harboring a pheochromocytoma may be accurately diagnosed, but potentially dangerous increases in blood pressure may be minimized, by performing the glucagon test after alpha-adrenergic blockade.

Adrenal Gland Neoplasms↗
PubMed1988

Role of the beta 2 adrenoceptor in mediating positive inotropic activity in the failing heart and its relation to the hemodynamic actions of dopexamine hydrochloride.

In patients with severe congestive heart failure, it has been suggested that since myocardial beta 1 adrenoceptors are selectively down-regulated, activation of beta 2 receptors may be a preferable approach to augmenting contractility. Accordingly, dopexamine hydrochloride (1, 2 and 4 micrograms/kg/min) and dopamine (2 and 4 micrograms/kg/min) were administered to 8 patients with dilated cardiomyopathy. Left ventricular (LV) dimensions, thicknesses and pressures were obtained using simultaneous high-fidelity pressure measurements and echocardiographic recordings. LV contractility was assessed using the load-independent relation between LV end-systolic wall stress and rate-corrected velocity of fiber shortening. Cardiac index increased in a dose-related manner with both drugs, and was accompanied by a decline in systemic vascular resistance, a measure of peripheral arteriolar tone. LV end-diastolic pressure was unaltered except for a decrease from 29 +/- 6 to 19 +/- 5 mm Hg (p less than 0.017) at the highest dose of dopexamine hydrochloride. Heart rate was unchanged during the infusion of dopamine but increased significantly with dopexamine hydrochloride. LV end-systolic wall stress, a measure of LV internal load, decreased with both drugs. With dopamine, a dose-dependent positive inotropic effect was observed. Dopexamine hydrochloride, at the 4 micrograms/kg/min infusion dose, exerted a mild positive inotropic effect comparable to that noted with dopamine at 2 micrograms/kg/min. Thus, dopamine and dopexamine hydrochloride improved overall LV performance. With dopamine, a substantial positive inotropic effect occurred in association with a reduction in LV afterload. The increased cardiac index observed with dopexamine hydrochloride was due primarily to peripheral vasodilatation and a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Reduced specificity of the clonidine suppression test in patients with normal plasma catecholamine levels.

Although originally devised to discriminate between patients with pheochromocytoma and those with elevated plasma catecholamine levels for other reasons, the clonidine suppression test has recently been used in patients with normal resting catecholamine levels. Upon review of 49 patients evaluated for pheochromocytoma, 26 had elevated plasma norepinephrine levels and underwent clonidine suppression testing. Only one of 13 patients with sustained elevated norepinephrine levels before clonidine administration had a false-positive clonidine test result, in contrast to five of 13 patients whose pre-clonidine norepinephrine levels had decreased into the normal range. This difference was statistically significant (by chi-square) at p less than 0.05. Clonidine suppression testing for pheochromocytoma should be performed only in patients with elevated catecholamine levels, because it carries a higher false-positive rate in patients with normal resting norepinephrine levels; a more accurate diagnosis may be made in such patients using glucagon stimulation tests.

Adrenal Gland Neoplasms↗
PubMed1988

Effects of selective dopamine-1 receptor activation on intraocular pressure in man.

The lack of specific agonists and antagonists has, until recently, precluded investigation of a role for dopamine receptors in the control of intraocular pressure. In the present study, we have examined the effects of fenoldopam, a novel selective dopamine1 (DA1) receptor agonist, on intraocular pressure, in eight healthy human volunteers. Fenoldopam, infused intravenously at 0.5 micrograms kg-1 min-1, increased intraocular pressure from 14.6 +/- 0.9 to 17.6 +/- 1.4 mmHg (P less than 0.05) while a control saline infusion had no effect. Pupil diameter and blood pressure did not change. In the same subjects, i.v. norepinephrine or angiotensin II both increased intraocular pressure--from 13.8 +/- 1.4- to 17.6 +/- 1.4 mmHg and from 13.4 +/- 1.3- to 17.5 +/- 1.7 mmHg respectively (P less than 0.05), and mean arterial pressure by about 20 mmHg. These data suggest that: (1) DA1 receptor activation can modulate intraocular pressure; (2) the intraocular pressure effects of the DA1 receptor agonist, fenoldopam, are independent of changes in systemic blood pressure, in contrast to those of norepinephrine or angiotensin II where intraocular and systemic blood pressures increase in parallel; (3) the ability of a DA1 receptor antagonist to lower intraocular pressure merits investigation.

Adolescent↗
PubMed1988

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma.

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma are two of the most common acute complications of diabetes. The pathophysiologic changes that occur in both disease states represent an extreme example of the super-fasted state. The physiology of the fed and fasted state, evaluation, therapeutic issues, recommendations for therapy, immediate follow up care, and complications of therapy are reviewed for both syndromes.

Diabetic Coma↗
PubMed1988

The role of alpha-adrenoceptor blockade in the antihypertensive effects of fenoldopam in humans.

Fenoldopam, a dopamine-1 receptor agonist, has been reported to exhibit alpha-adrenoceptor-blocking actions in intact and isolated animal preparations. To determine whether alpha-adrenoceptor blockade contributes to its antihypertensive properties in humans, the effects of fenoldopam on the pressor responses to norepinephrine and angiotensin II were compared in eight normal volunteers. Fenoldopam (0.5 micrograms/kg/min) shifted the dose-response curves for both agonists to the right (p less than 0.05). Dose ratios for an increase in mean blood pressure of 10 mm Hg were 3.3 +/- 0.9 for norepinephrine and 3.2 +/- 0.6 for angiotensin II (p not significant). Consequently, fenoldopam is not a selective alpha-adrenoceptor antagonist at therapeutic concentrations in humans.

Adrenergic alpha-Antagonists↗
PubMed1988

Evaluation of the Suntech Accutracker. A novel noninvasive ambulatory blood pressure monitor.

The "Accutracker," a novel ambulatory blood pressure monitor based on auscultation triggered by the electrocardiographic R wave, was evaluated by comparing its blood pressure readings with those obtained by direct auscultation. Simultaneous measurements were made (in 24 volunteers, by 4 trained observers) using a Y connector so that the Accutracker and a mercury sphygmomanometer were in parallel. Average blood pressure by direct auscultation (215 readings) was 129.1 +/- 12.0/77.8 +/- 14.4, and by Accutracker was 130.9 +/- 13.0/75.9 +/- 14.5 mm Hg (P less than 0.01). The Accutracker overestimated systolic blood pressure by 1.7 +/- 5.8 and underestimated diastolic blood pressure by 1.9 +/- 7.6 mm Hg. The average difference between pairs of readings was 5.0 mm Hg for systolic and 5.5 mm Hg for diastolic pressure. These data indicate that the concordance of blood pressure readings recorded by Accutracker and direct auscultation is sufficient to justify its use in noninvasive ambulatory blood pressure monitoring.

Auscultation↗