Search PubMed⌕ Search

Biomedical subjects

N D Vlachakis

Publications and source records attributed to N D Vlachakis.

At least 37 records · Page 2Linked to original sources

Enzymatic deconjugation of catecholamines in human and rat plasma and red blood cell lysate.

We have developed a method for enzymatic hydrolysis of both sulfated and glucuronidated catecholamines in plasma and red blood cell lysate. Hydrolysis occurs in the course of the radioenzymatic assay for catecholamines. In human plasma, catecholamines are conjugated almost entirely with sulfate while, in rat plasma, glucuronides are the main conjugates of epinephrine and dopamine but not norepinephrine. Rat plasma contains less percent conjugated catecholamine than human plasma. Human red blood cell lysate contains less conjugated catecholamine than plasma, whereas free E in lysate exceeds that of plasma and free NE has same level both in sulfated + glucuronidated) catecholamines and the nature of conjugated catecholamines.

Animals↗

Response of thiazide-induced hypokalemia to amiloride.

The effects of amiloride hydrochloride on thiazide-induced hypokalemia were evaluated. In metabolic balance studies, amiloride reversed thiazide-induced urinary potassium loss, restored plasma bicarbonate concentration and pH to pretreatment levels, and produced further increases in aldosterone secretion. Effects of long-term administration of hydrochlorothiazide and an amiloride-hydrochlorothiazide combination were compared in outpatients who had experienced thiazide-induced hypokalemia while receiving oral potassium supplements. After eight weeks, those given hydrochlorothiazide alone had an average serum potassium level of 3.01 +/- 0.08 mEq/L). Those given the amiloride-hydrochlorothiazide combination had an average serum potassium level of 3.75 +/- 0.008 mEq/L, not significantly different from the control value (3.82 +/- 0.08 mEq/L). Both groups had increased plasma aldosterone concentrations and plasma renin activity. The potassium-conserving effect of amiloride persisted with extended therapy.

Aldosterone↗

Medroxalol combined with hydrochlorothiazide in the treatment of hypertension.

The antihypertensive effect and safety of hydrochlorothiazide administration as a single drug and together with medroxalol were determined in 20 patients with primary hypertension. Following two biweekly intervals on placebo and hydrochlorothiazide, medroxalol was started at 100 mg three times a day and titrated against blood pressure response up to a maximum of 300 mg three times a day. In nine patients the effect of the single and the combined drug therapy on blood pressure during isometric handgrip exercise, on plasma renin activity, and on plasma catecholamines and their deaminated metabolites was investigated. The administration of hydrochlorothiazide was associated with a significant decrease in blood pressure, but heart rate did not change. The addition of medroxalol produced a substantial decrease in blood pressure and heart rate in both the recumbent and upright positions (P less than 0.001). Due to careful titration of medroxalol, orthostatic hypotension was observed only in one patient. Neither hydrochlorothiazide alone nor the combined drug regimen prevented or diminished the rise in blood pressure with exercise. Although plasma renin activity decreased during the combined drug therapy, there was no correlation between the initial levels or the change in plasma renin activity and the extent of decrease in blood pressure. The concentration of plasma epinephrine increased during the combined drug period, whereas catecholamine metabolites increased significantly during both periods of the study. It is concluded that medroxalol combined with hydrochlorothiazide constituted a potent and safe antihypertensive therapy for the duration of the present study.

Adrenergic alpha-Antagonists↗

Hemodynamic effect of lofexidine with a diuretic in hypertension.

We measured the first dosage effect and the long-term effect of lofexidine on blood pressure, heart rate, plasma catecholamines, and their major metabolites in 16 patients with primary hypertension who were receiving 50 mg hydrochlorothiazide twice a day while they were recumbent and upright and during isometric handgrip contraction. We also measured the first dosage effect of lofexidine on forearm blood flow and its long-term effect on plasma renin activity. Lofexidine, both in a single dose and after long-term therapy, induced a substantial fall in blood pressure of patients in recumbent and upright positions, whereas it decreased heart rate in both positions only during long-term dosing. Lofexidine did not prevent or diminish the pressure and heart rate rise by isometric handgrip contractions. Single and long-term lofexidine dosing induced a fall in plasma levels of catecholamines and their metabolites. There was a positive correlation between the fall in blood pressures and the reduction in plasma norepinephrine during long-term therapy. There was a positive correlation between the decrease in blood pressure induced by single doses and by long-term dosing, which suggests that lofexidine in a single dosage at the start of therapy may facilitate identification of responders.

Adult↗

Catecholamines and their major metabolites in plasma and cerebrospinal fluid of man.

In 36 patients undergoing elective surgery under spinal anesthesia, plasma and cerebrospinal fluid (CSF) concentrations of catecholamines and their major metabolic products were determined. The development of specific and sensitive radioenzymatic assays make these determinations possible. The levels of norepinephrine, epinephrine, and the O-methylated metabolite, normetanephrine, were greater in the plasma then the CSF, although the difference was significant for norepinephrine and epinephrine only (P less than 0.01 for both) On the other hand the levels of both deaminated metabolites dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA) were greater in the CSF the in plasma, but the difference was significant for DOPEG only (P less than 0.01). Although there was a positive and significant correlation between the levels in plasma and CSF of all these compounds, their concentrations in CSF may reflect metabolism of catecholamines in the central nervous system.

Adult↗

Hypertension and propranolol therapy: effect on blood pressure, plasma catecholamines and platelet aggregation.

The effects of propranolol on blood pressure, plasma catecholamine concentration and platelet aggregation were examined in 16 patients with uncomplicated primary hypertension. The patients were studied at rest, during isometric handrip stress and 48 hours after sudden discontinuation of propranolol therapy. Plasma catecholamine concentration and platelet aggregation studies were also carried out in 11 age-matched normotensive and healthy subjects at rest. Plasma catecholamine concentration and platelet aggregation were greater in the hypertensive than in the normotensive subjects, but the difference reached statistical significance for aggregation only. Exercise significantly increased catecholamines and platelet aggregability. The administration of propranolol (240 mg/day) produced a significant decrease in systolic and diastolic blood pressue and in aggregation (the percent of light transmission at 1 microM adenosine diphosphate, at rest) and a significant increase in catecholamine concentration. However, propranolol did not prevent the changes in all these variables with exercise. The abrupt discontinuation of propranolol was not associated with any subjective or objective untoward cardiovascular effect or abnormal changes in plasma catecholamines. However, in some patients the platelet aggregation studies demonstrated a hyperaggregable state, which may be due to a state of supersensitivity of platelets to circulating catecholamines.

Blood Pressure↗

Sympathetic nervous system tonicity and post-coronary artery bypass hypertension.

To elucidate the pathogenesis of hypertension following coronary bypass surgery, blood pressure and plasma catecholamine concentration were measured in 28 patients with coronary artery disease who were undergoing myocardial revascularization procedures. Measurements were obtained on arrival in the operating room and 1 and 4 h after surgery. One hour after surgery, plasma norepinephrine (NE) increased significantly by 495 +/- 108 pg/ml (P less than 0.001) in the coronary artery disease group which developed hypertension, but the increase was not significant in the coronary artery patients who remained normotensive after surgery. However, 4 h after surgery, plasma NE increased significantly and to the same extent in both coronary artery disease groups, regardless of the change in blood pressure. Plasma epinephrine (E) also increased significantly 1 and 4 h after surgery in both groups. The observed change in plasma catecholamine concentration is direct evidence that the stress of surgery is a potent adrenergic stimulus, but the hemodynamic significance of the plasma catecholamine change remains unclear.

Blood Pressure↗

Increased plasma normetanephrine in spontaneously hypertensive rats.

Plasma catecholamine and total plasma normetanephrine concentrations were determined in 11 spontaneously hypertensive rats (SHR) and in 11 age and sex matched Wistar Kyoto control rats (WKy). Plasma norepinephrine concentration, obtained from tail vein blood of restrained rats, was 356 +/- 67 pg/ml in SHR and 297 +/- 61 in WKy (NS), whereas epinephrine was 1079 +/- 117 in SHR and 695 +/- 107 in WKy (p < 0.05). Total plasma normetanephrine concentration was 1825 +/- 472 pg/ml in SHR and 535 +/- 109 in WKy (p < 0.02). Since normetanephrine is mainly an extraneuronal metabolite of norepinephrine, its plasma concentration could reflect the amount of the neurotransmitter which reaches effector cell sites suggesting enhanced sympathetic function accounts for blood pressure elevation in SHR. A simple and specific radioenzymatic assay for measurement of total plasma normetanephrine in rat was described.

Animals↗

Plasma normetanephrine measurements for detection of pheochromocytoma in patients with hypertension.

We describe a simple and specific radioenzymatic assay for measurement of total plasma normetanephrine (NMN), which is an extension of a previously developed procedure for measuring of urinary NMN. Plasma NMN is deconjugated by acid hydrolysis at pH 1.0 and boiled for 20 min. The assay is based on the conversion of NMN to its N-methylated, tritiated derivative metanephrine (3H-MN), utilizing phenylethanolamine N-methyltransferase and S-adenosyl-[3H]methionine. The assay is rapid, sensitive and results can be obtained in less than 4 h. Many antihypertensive drugs tested did not interfere with the assay. This assay could be used for detection of pheochromocytomas in patients with hypertension.

Adrenal Gland Neoplasms↗