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Biomedical subjects

E P MacCarthy

Publications and source records attributed to E P MacCarthy.

At least 37 records · Page 2Linked to original sources
PubMed1984

Natriuretic and water diuretic effects of central alpha 2-adrenoceptor agonists.

Methyldopa, clonidine, and a more recently developed drug, guanabenz, have similar antihypertensive mechanisms, predominantly suppression of central sympathetic outflow by alpha 2-receptor agonism and consequent reduction in peripheral sympathetic activity. Recent studies clearly demonstrate an important role of the sympathetic nervous system in the control of sodium excretion. Therefore, the interrelationships between the use of central alpha-adrenergic agonists as antihypertensive agents and their influence on renal handling of sodium are important. Certain problems accompany the use of the older centrally acting drugs as monotherapy. As a response to the hypotensive effects of these drugs, certain renal adaptations take place which presumably are homeostatic attempts to restore blood pressure and plasma volume to baseline, but which lead to a positive sodium balance, antihypertensive tolerance and occasionally the development of overt edema. The high incidence of tolerance has led most physicians to use diuretics on a routine basis, superimposing the side effects of diuretics and compromising compliance. The potential natriuretic properties of guanabenz appear to counter-balance the sodium retaining side effects commonly seen with other centrally acting and vasodilating antihypertensive drugs. This property, therefore, makes this agent a scientifically interesting and potentially useful therapeutic drug for the therapy of high blood pressure.

Adrenergic alpha-Agonists↗
PubMed1984

Abnormalities of fibrinolysis in essential hypertension.

A highly-standardized plate method was used to study fibrinolytic profiles in 14 patients with essential hypertension and 245 normotensive healthy control subjects. Compared with the normotensive group, the group with essential hypertension showed a defect in fibrinolysis, as evidenced by a significant increase in the mean level of inhibitor of plasminogen activation, and a subset of the hypertensive patients also showed a significant decrease in the mean level of vascular plasminogen activator. There were no significant differences between the two groups in relation to plasma fibrinogen level, total fibrinolytic activity and plasmin inhibitor. The alterations in inhibitor of plasminogen activation and vascular plasminogen activator in the patients with essential hypertension may reflect a defect in the fibrin-clearing mechanism and, perhaps, contribute to the vascular complications of hypertension.

Adult↗
PubMed1984

Natriuretic and water diuretic effects of guanabenz, a central alpha-2 agonist.

I should like to preface my concluding remarks by noting that our observations are still of a preliminary nature. Guanabenz, an acute central adrenergic inhibitor produces in human subjects (previously volume expanded with saline) changes similar to those previously described in animals, namely a rise or no change in GFR, an enhancement of water diuresis, and a significant natriuresis. Within one week of the acute study and during chronic administration of guanabenz, all of these changes were reversed: GFR, the magnitude of the water diuresis and the enhanced sodium excretion had returned to the baseline pre-guanabenz levels, indicating that certain adaptive, restorative mechanism were operative. One may conclude, however, that the potential natriuretic properties of guanabenz (even during chronic administration), counter-balance the sodium retaining side effects commonly seen with other centrally acting and vasodilating antihypertensive drugs. This property, therefore, makes this agent a scientifically interesting and potentially useful therapeutic drug in the treatment of high blood pressure.

Adult↗
PubMed1983

Human mononuclear cell modulation of endothelial cell proliferation.

Endothelial cell proliferation is a histologic characteristic of several forms of nephritis characterized by infiltration of the glomerulus with mononuclear cells. To investigate the mechanism mediating this event, human endothelial cells isolated from umbilical veins and cultured in vitro were incubated with supernatants of cultured human mononuclear cells. Supernatants from mononuclear cells exerted a dose-dependent stimulatory effect on endothelial cell proliferation. The stimulatory effect of supernatant was almost entirely removed by prior depletion of mononuclear cells of monocytes by adherence, suggesting that a monocyte product was responsible for the activity. To investigate the nature of the ligand responsible, partially purified human interleukin I added to endothelial cell cultures was found to stimulate cellular proliferation.

Cell Adhesion↗
PubMed1980

Prediction of response to antihypertensive therapy with prazosin.

Blood-pressure responses and changes in plasma drug concentration were studied in 11 hypertensive patients after an initial oral dose of 2 mg of prazosin. Subsequently, blood pressure was monitored during long-term treatment with prazosin. The prazosin reactivity index, a value derived during the first-dose study, appeared to predict the long-term antihypertensive effect of prazosin alone or prazosin combined with bendrofluazide.

Adult↗
PubMed1979

Indomethacin-induced hyperkalaemia.

A patient with mild chronic renal failure developed significant hyperkalaemia while receiving indomethacin therapy. The hyperkalaemia, which was reversed by discontinuing indomethacin, is attributed to a drug-induced defect in the cellular uptake of potassium.

Humans↗
PubMed1979

Responsiveness to prazosin in renal failure.

1. The fall in blood pressure produced by a test dose of prazosin was greater in a group of patients with chronic renal failure than in a group with normal renal function. 2. This difference could not be attributed to increased reactivity, measured as the slope of the regression line relating mean blood pressure and plasma prazosin concentration, nor to retarded elimination of the drug. 3. The enhanced antihypertensive effect of prazosin in renal failure appears to reflect changes in the bioavailability or distribution of the drug, which result in higher drug concentrations for a given dose.

Adult↗
PubMed1979

False-negative saralasin responses in renovascular hypertension.

Blood pressure responses to the infusion of saralasin and plasma renin levels were measured in 31 hypertensive patients following preparation with frusemide. Five patients had unilateral renal artery stenosis, with renal vein ratios lateralising strongly to the affected side. Saralasin produced depressor responses in 3 of these but failed to evoke significant effects in the other 2, despite the fact that in both cases hypertension was subsequently alleviated by renal bypass surgery. A further period of more severe sodium depletion increased plasma renin levels and the depressor effect of saralasin, but did not help to differentiate renal artery stenosis from other forms of hypertension.

Adult↗
PubMed1978

Labetalol in hypertensive emergencies.

Labetalol, a combined alpha-blocking and beta-blocking agents, was administered by intravenous bolus to six severely hypertensive patients. The blood pressure response was unsatisfactory in every case. It is concluded that intravenous administration of labetalol is not useful in hypertensive emergencies which occur in patients who are already receiving other antihypertensive agents.

Adult↗
PubMed1978

Comparative haemodynamic effects of clonidine and guanfacine.

Dose-response relationships were established for the acute effects on arterial pressure and heart rate of the antihypertensive agents, clonidine and guanfacine, administered intravenously or intramuscularly to anaesthetized rats. The intramuscular route appeared to be preferable to the intravenous, for the direct pressor potency of each drug was thereby greatly reduced in relation to the hypotensive efficacy. The potency of clonidine was 10-20 times that of guanfacine, but the same maximal fall in blood pressure was obtained with either agent administered by either route. Both agents caused a marked, dose-related suppression of plasma renin activity. When either clonidine or guanfacine was administered twice daily for 3 weeks and then discontinued, a phase of blood pressure overshoot with tachycardia commenced within 24 hr of the last injection. These withdrawal effects were more evident in guanfacine-treated rats than in clonidine-treated rats.

Animals↗