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Biomedical subjects

N Alexander

Publications and source records attributed to N Alexander.

At least 91 records · Page 5Linked to original sources
PubMed1984

Acute effect of labetalol on blood pressure in relation to the sympathetic nervous system and plasma renin activity.

A single oral dose of 300 mg labetalol was given to 10 subjects with uncomplicated primary hypertension; its effects on blood pressure, heart rate (HR), plasma renin activity (PRA), and plasma concentration of catecholamines and of their major metabolites, octopamine ( OTP ), and dopamine-beta hydroxylase (DbH) were investigated. Although HR did not change after dosing, both systolic and diastolic blood pressure decreased in 2 hr and remained below control up to 12 hr. There was symptomatic orthostatic hypotension in two subjects in the first 2 hr after dosing. PRA decreased in the first 2 hr and followed a gradual rise that became significant at 24 hr. Although DbH did not change, plasma concentrations of norepinephrine (NE) and its major metabolites and of OTP increased between 2 and 4 hr after dosing and remained elevated up to 12 hr. There was no correlation between change in blood pressure and control levels or changes of PRA or NE concentrations.

Blood Pressure↗
PubMed1984

Role of conjugation and red blood cells for inactivation of circulating catecholamines.

We investigated the extent of catecholamine (CA) conjugation in plasma and accumulation inside red blood cells (RBCs) after forced immobilization of the rat. A control blood sample was obtained from undisturbed rats resting in home cages via an indwelling aortic catheter. Then rats were immobilized for 2 h, and blood samples were taken during stress at 15 min and 2 h and at 30 min poststress. Both sulfate and glucuronide conjugates were deconjugated by enzymatic hydrolysis and measured by radioenzymatic thin-layer chromatographic methods. In plasma of resting rats, the major conjugate of norepinephrine (NE) is sulfate and that of epinephrine (E) and dopamine (DA) is glucuronide; total conjugates in plasma are 53, 57, and 97% of total NE, E, and DA, respectively. During stress, sulfate conjugates of NE, E, and DA increased significantly along with free NE, E, and DA. DA glucuronide unexpectedly declined at 2 h of stress and 30 min poststress. Concentrations of free CAs rose in RBCs during stress, as did NE sulfate, the only conjugate present in RBC lysate. We conclude that both CA conjugation and RBC accumulation are enhanced when large amounts of free CA enter the circulation as a result of immobilization stress and that the relative importance of these inactivation pathways is different for the three CAs.

Animals↗
PubMed1984

Role of conjugation and red blood cells for inactivation of circulating normetanephrine.

Plasma and red blood cell (RBC) concentrations of normetanephrine (NMN), in both free and glucuronide-conjugated forms, were measured before, during, and after forced immobilization, an intense stressor of the sympathoadrenal system of rats. In this study NMN glucuronide was deconjugated by enzymatic hydrolysis; free and total NMN were assayed by radioenzymatic, thin-layer chromatographic procedures. In plasma, free NMN and NMN glucuronide are 777 +/- 99 and 792 +/- 74 pg/ml, respectively, when rats are at rest. Both free NMN and NMN glucuronide increased about 200% after 15 min of stress; in absolute amounts, increases were equivalent to that of the simultaneous increase in norepinephrine (NE). At 2 h of stress, NMN glucuronide, but not free NMN, increased further and significantly. The mean concentration of RBC-free NMN is about 50 times higher than that of plasma-free NMN, and it did not change significantly during stress; RBCs do not contain conjugated NMN. RBC NMN levels showed a strong correlation with RBC catechol methyltransferase activity. The latter seems to operate under conditions of substrate saturation; an acute release of NE leads to temporary storage of NE in RBCs but not conversion to NMN. The results indicate that conjugation of NMN with glucuronic acid is an important route for inactivation of plasma NMN formed during forced immobilization stress, whereas free NMN does not accumulate in RBCs during stress.

Animals↗
PubMed1983

Catecholamines and phenylethanolamine N-methyltransferase in selected brain nuclei and in the pineal gland of neurogenically hypertensive rats.

Catecholamines (dopamine, norepinephrine and epinephrine) and the epinephrine-forming enzyme, phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28) were measured in selective brainstem and hypothalamic nuclei and in the pineal gland of acutely (3 days after operation) and chronically (2 weeks after operation) neurogenically hypertensive (sinoaortically denervated, SAD) rats. Alterations in catecholamine levels and in PNMT activity were restricted to a few brain nuclei and the pineal gland, and were dependent on the time elapsed since SAD. Our results suggest a participation of discrete hypothalamic norepinephrine and brainstem epinephrine neurons in the development and maintenance of neurogenic hypertension.

Animals↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1982

Familial insensitivity of the pituitary and periphery to thyroid hormone: a case report in two generations and a review of the literature.

A clinically euthyroid 2-yr-old girl was found to have diffuse goiter that measured 3 X 5.5 cm with a prominent systolic bruit. Serum free T4 (3.4 ng/dl) and serum T3 (360 ng/dl) remained elevated for the next 10 months even though she remained clinically euthyroid. Elevation of serum free T4 (3.0 ng/dl) and serum T3 (265 ng/dl) was also present in the 24-yr-old nongoitrous mother who had symptoms and signs of hypothyroidism. Following intravenous injection of TRH, basal TSH levels of 2.7 and 2.8 microunits/ml increased to peak values of 17 and 21 microunits/ml at 30 min in the daughter and mother, respectively. Administration of exogenous T3 followed by sequential testing with boluses of TRH revealed retention of TSH responsiveness in both daughter and mother during pretreatment with dosage regimens of T3 below 125 micrograms daily. Maintenance of TSH responsiveness to TRH in the presence of elevated levels of serum free T4 and serum T3 indicates relative pituitary insensitivity to thyroid hormone which could be overridden by increasing the circulating levels of serum T3 three to fivefold over the already elevated basal levels. The absence of clinical signs of thyrotoxicosis indicates peripheral insensitivity to thyroid hormone with elevated circulating concentrations presumptively compensating for the defect. Resistance to thyroid hormone in two generations of the same family suggests genetic inheritance, and is concordant with four earlier reports of familial aggregation in this syndrome.

Adult↗
PubMed1982

Blood pressure and sodium excretion in the sinoaortic denervated rat during chronic high and low sodium intake and acute sodium loading.

We studied the effects of dietary sodium on the magnitude of hypertension in sinoaortic denervated (SAD) rats. Groups of SAD rats and sham operated (SO) controls drank tap water and received chows with different amounts of sodium: low (0.08%), regular (0.4%), high (3%) or very high (7%) sodium; other groups, some after unilateral nephrectomy, received regular chow and 1% saline to drink. These various sodium regimens were started before operations and were continued for at least 12 weeks after SAD and SO. Weekly systolic tail-cuff pressures of SAD rats were significantly higher throughout the 12 week postoperative period than those of SO rats regardless of sodium regimen (p less than 0.05 to less than 0.01). Analysis of variance indicated no significant differences between pressures of SAD rats on regular or low sodium chows and those receiving any of the high sodium regimens. When SAD rats were switched from regular to high sodium diets no significant change was induced in systolic pressures. We then examined renal sodium excretion in response to oral sodium loading or to intravenous saline infusion in groups of SAD and SO rats. Both types of studies revealed that SAD rats excreted the extra sodium significantly faster than SO rats. We conclude that hypertension induced by SAD is not dependent on the amount of sodium in the diet and that the magnitude of hypertension is not increased by chronic high sodium intake. The rapid excretion of sodium suggests SAD rats have an enhanced sensitivity to activation and/or to effects of neural and/or humoral factors affecting renal sodium excretion.

Animals↗
PubMed1982

Intermittent long-term administration of a potent gonadotropin-releasing hormone agonist in normal men.

The effects on pituitary-gonadal function of the potent gonadotropin-releasing hormone agonist D-trp6-pro9-n-ethylamide-LHRH (LRFA), 50 micrograms subcutaneously every 4th day for 10 weeks, were evaluated in seven normal men. A modest rise in mean serum LH levels was noted during the treatment period. Mean serum FSH levels were unchanged. Mean plasma testosterone (T) levels remained at 3.1 ng/ml or above. Sperm density during the control period varied widely within and between subjects, with a mean range of 69-137 million/ml. The mean sperm density fell to a nadir of 40 million/ml during treatment, but no consistent pattern was observed for each subject, with values varying between 4 and 368 million/ml. Elevated LH and T values were observed on eight and seven occasions, respectively, in five subjects, and corresponded to blood samples drawn 24 and 48 h after the last LRFA injection. Depressed T values were observed on 10 occasions in six patients, and in all but one, corresponded to blood drawn 72 and 96 h after the last injection. One subject had daily blood samples drawn at the start of and 4 weeks after beginning therapy. An agonist effect on LH, FSH, T, and estradiol was observed both times, although the effect was blunted on the second occasion. We conclude that treatment every 4 day with LRFA does not appear to be a promising regimen to induce consistent suppression of the pituitary-gonadal axis in man.

Adult↗
PubMed1981

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↗
PubMed1981

Reversible inhibition of testicular steroidogenesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men: an approach toward the development of a male contraceptive.

We studied the antifertility effects of a potent gonadotropin-releasing hormone agonist, D-Trp6-Pro9-N-ethylamide-LHRH (LHRHA) in eight normal men, who received daily subcutaneous injections for six to 10 weeks. Plasma testosterone levels fell substantially in all eight. Plasma 17-hydroxyprogesterone and serum estradiol-17 beta levels decreased concordantly with plasma testosterone. Impotence developed in five men between the sixth and seventh weeks of treatment, with resolution in each case within two weeks of stopping treatment. Serum gonadotropin levels also fell during treatment, briefly rebounding above basal levels when therapy ended. Sperm density and motility fell t a nadir during the seventh to 18th week after therapy. In six subjects sperm levels fell to 6 X 10(6) sperm per milliliter or less, and in the other two they decreased 70 and 86 per cent below basal mean values. Sperm density returned to pretreatment levels in all men during the 10-to-14-week recovery period. These results are consistent with LHRHA-induced pituitary "desensitization" but do not exclude a direct inhibitory effect of LHRHA on testicular steroidogenesis and spermatogenesis.

Adult↗
PubMed1981

Genetic difference in the sympathetic nervous activity and susceptibility to atherosclerosis in pigeon.

Norepinephrine (NE) accumulation, dose response to NE and NE content were studied in the aortas of White Carneau (WC) and Show Racer (SR) pigeons in order to determine if a correlation exists between the atherosclerosis susceptibility of WC and atherosclerosis resistance of SR with the degree of sympathetic nerve ending activity. In addition, the age factor was included by comparing results in 4-14 month-old and 5-year-old animals. NE accumulation by abdominal aorta samples from SR pigeons of both age groups and by thoracic segments from 5-year-old SR was significantly higher than that by WC pigeon samples. The difference in NE accumulation had lower P-values in older than in younger pigeons. Maximal contraction of SR abdominal aorta was significantly higher than that of WC samples. The ED50 to exogenous NE decreased with age in both strains but the decrease was statistically significant only in WC strain. Finally, NE content of abdominal aorta segments was significantly higher in SR than in WC pigeons. Ne content of thoracic aorta did not differ in the 2 strains. The results complement our previous work indicating that sympathetic nerve endings in the vessel wall may have a trophic influence which modulates the metabolic pattern of the arteries. Thus, atherosclerosis and perhaps age, are related degenerative vascular changes associated with reduced indices of sympathetic activity.

Aging↗
PubMed1980

Cardiovascular responses to central catecholamines of sinoaortic denervated rats.

The characteristic movement-related arterial pressure dips seen in sinoaortic-denervated (SAD) animals suggested they should have enhanced vasodepressor responses to central adrenergic agonists. This was tested by comparing the reductions in mean arterial pressure and heart rate of conscious sham-operated (SO) and SAD rats during injections of norepinephrine (NE) or epinephrine (E) (0.25--16 micrograms) into the fourth cerebral ventricle. NE produced significantly greater maximum vasodepression and, simultaneously, significantly less bradycardia in SAD than SO rats. E, like NE, produced significantly more vasodepression in SADs, but unlike NE, elicited the same magnitude of bradycardia in both groups. The pressures were reduced and the log-dose pressure response curves shifted to the left in SAD rats. These results provide indirect evidence that central sensitivity to intracerebroventricular catecholamines is altered in SAD rats and that the direction of change in sensitivity is divergent for pressure and heart rate.

Animals↗