Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 109 records · Page 6Linked to original sources

PubMed1985

Pentobarbital effects on plasma catecholamines: temperature, heart rate, and blood pressure.

The effects of intravenous pentobarbital were studied in dogs. Plasma pentobarbital concentrations were inversely related to epinephrine and norepinephrine concentrations. Plasma catecholamines appeared fully suppressed at pentobarbital levels greater than 25-30 micrograms/ml. Furthermore, pentobarbital levels were negatively related to rectal temperature, heart rate, and mean blood pressure. The methods of pentobarbital administration influenced plasma pentobarbital as well as epinephrine and norepinephrine levels, temperature, heart rate, and blood pressure. These observations suggest the possibility that pentobarbital inhibits the sympathetic nervous system, which in turn may affect temperature, heart rate, and blood pressure. Because pentobarbital anesthesia affects plasma catecholamine concentrations, the regimen used in animal models requires consideration when interpreting data potentially influenced by the sympathetic nervous system.

Animals↗

PubMed1985

Blood pressure and norepinephrine spillover during propranolol infusion in humans.

To determine whether a reflex increase of sympathetic nervous system activity contributes to maintenance of blood pressure during acute beta-adrenergic blockade, we measured plasma norepinephrine levels and norepinephrine kinetics during propranolol administration. During a 90-min infusion of propranolol (10 mg iv + 80 micrograms/min) in 12 normal subjects, heart rate fell from 56 +/- 2 to 49 +/- 2 (SE) beats/min (P less than 0.001), but there was no fall in mean arterial blood pressure (84 +/- 3 mmHg before and 86 +/- 3 mmHg after propranolol). Arterial plasma norepinephrine levels rose from 183 +/- 20 to 250 +/- 29 pg/ml during propranolol (P less than 0.001), suggesting increased sympathetic vasoconstrictor tone. However, isotope dilution studies using tritiated norepinephrine infusion showed that arterial plasma levels of tritiated norepinephrine rose from 743 +/- 78 to 1,002 +/- 101 dpm/ml during propranolol (P less than 0.001), indicating a reduction in the rate of norepinephrine clearance from plasma. The calculated fall in clearance from 1.90 +/- 0.13 to 1.42 +/- 0.11 1/min (P less than 0.001) entirely accounted for the rise in plasma norepinephrine, since the calculated rate of norepinephrine spillover into plasma remained at the base-line level of 340 +/- 40 ng/min during propranolol. In control studies on four subjects, arterial plasma norepinephrine levels and norepinephrine kinetics did not change from base line during the control period. We conclude that maintenance of blood pressure during propranolol infusion is not due to a reflex generalized increase of sympathetic vasoconstrictor tone.

Adult↗

PubMed1985

Hemodynamic effects of epinephrine: concentration-effect study in humans.

The hemodynamic effects of three different infusion rates of epinephrine (25, 50, or 100 ng X kg-1 X min-1 for 14 min) were examined in 10 normal human subjects. Ejection fraction and changes in cardiac volumes were assessed by radionuclide ventriculography. Plasma epinephrine was increased to levels that spanned the normal physiological range (178 +/- 15, 259 +/- 24, and 484 +/- 69 pg/ml, respectively). Epinephrine infusions resulted in dose-dependent increases in heart rate (8 +/- 3, 12 +/- 2, and 17 +/- 1 beats/min, mean +/- SE) and systolic pressure (8 +/- 1, 18 +/- 2, and 30 +/- 6 mmHg). Although epinephrine infusions had minimal effects on end-diastolic volume, there were significant increases in stroke volume (+26 +/- 2, 31 +/- 4, and 40 +/- 4%), ejection fraction (+0.10 +/- 0.01, 0.14 +/- 0.02 and 0.16 +/- 0.03 ejection fraction units), and cardiac output (+41 +/- 4, 58 +/- 5, and 74 +/- 1%). These increases in left ventricular performance were associated with a decreased systemic vascular resistance (-31 +/- 3, -42 +/- 2, and -48 +/- 8%). Supine bicycle exercise resulted in similar plasma epinephrine levels (417 +/- 109 pg/ml) and similar changes in stroke volume, ejection fraction, and systemic vascular resistance but greater increases in heart rate and systolic blood pressure. Since infusion-associated hemodynamic changes occurred at plasma epinephrine levels commonly achieved during many types of physical and emotional stress, epinephrine release may have an important role in regulating systemic vascular resistance, stroke volume, and ejection fraction responses to stress in man.

Adult↗

PubMed1985

Prostaglandin E2 metabolite levels during diabetic ketoacidosis.

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.

Adult↗

PubMed1985

Insulin resistance and impaired insulin secretion in subjects with histories of gestational diabetes mellitus.

NIDDM is characterized by decreased insulin secretory responses to glucose and to nonglucose stimuli, hyperglucagonemia, and decreased tissue sensitivity to insulin. However, it has been unclear which of these abnormalities, if any, precedes the others. Since women with histories of gestational diabetes mellitus (GDM) are at high risk for eventual development of NIDDM, we measured B- and A-cell function and tissue sensitivity to insulin in eight normoglycemic, postpartum women with recent histories of GDM and in eight control subjects pair-matched for age and percent of ideal body weight. Fasting plasma glucose levels in subjects with former GDM tended to be slightly higher than in matched controls (98 +/- 3 versus 92 +/- 2 mg/dl, P = 0.07). Basal plasma insulin in subjects with former GDM was significantly higher than in controls (22 +/- 4 versus 14 +/- 2 microU/ml, P = 0.05). During an intravenous glucose tolerance test (IVGTT), relative first- and second-phase insulin responses to glucose were decreased in subjects with former GDM (2316 +/- 560 versus 7798 +/- 1036% of basal X min, P = 0.004; and 8340 +/- 946 versus 14,509 +/- 2556, P = 0.04). An index of sensitivity to insulin, SI, calculated from the IVGTT, was also lower in former GDM (1.23 +/- 0.69 X 10(-4) versus 3.58 +/- 0.78 X 10(-4) min-1/microU/ml, P = 0.001). Acute insulin responses to 5 g i.v. arginine were measured at plasma glucose levels of approximately 95, 215, and 600 mg/dl. The response at 600 mg/dl is termed the AIRmax and is used as an index of glucose-regulated insulin secretory capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Norepinephrine and MHPG levels in CSF and plasma in Alzheimer's disease.

Postmortem findings of decreased brain norepinephrine (NE) content and decreased locus ceruleus neuronal density have suggested a possible noradrenergic deficit in Alzheimer's disease (AD). We assessed CNS and peripheral noradrenergic function in patients with advanced AD, moderate AD, and age-matched normals by measuring NE and the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in CSF and plasma. Subjects were drug free for at least two weeks. Plasma and CSF NE and MHPG levels were significantly higher in patients with advanced AD than in either patients with moderate AD or normal controls, while values in the patients with moderate AD did not differ from those in normal controls. These findings do not support either a central or peripheral noradrenergic deficit in AD. Rather, they suggest increased CNS and peripheral noradrenergic activity in advanced stages of the disease.

Aged↗

PubMed1984

Plasma norepinephrine in normal young and aged men: relationship with sleep.

This study explored the relationship between age-related elevations of plasma norepinephrine (NE) levels (thought to reflect heightened sympathetic nervous system activity) and sleep. Plasma NE levels were consistently and significantly greater in 8 aged than 10 young men across a 24-hr study period. For both groups, plasma catecholamine levels remained stable near bedtimes and rise times and during spontaneous and experimentally induced nighttime awakenings; reversal of the sleep/wake pattern (nighttime wakefulness, daytime sleep) had little effect on the 24-hr plasma NE or sleep patterns, indicating that elevated NE cannot be attributed to altered sleep/wakefulness per se. The aged group had significantly more wakefulness and significantly higher plasma NE levels while in bed in all study conditions. These two variables were significantly correlated, suggesting that heightened sympathetic activity may fragment sleep with wakefulness in the aged.

Adult↗

PubMed1984

Effect of sodium salicylate on hormonal responses to hypoglycaemia in type II diabetics.

Prostaglandins and prostaglandin synthesis inhibitors are known to influence the secretion of a number of hormones. More specifically, sodium salicylate is known to increase insulin secretion in Type II diabetics in response to a glucose stimulus. To challenge the hypothesis that prostaglandins may be instrumental in a generalized defect of glucose recognition in Type II diabetics, the effect of sodium salicylate on the hormonal counter-regulatory response to insulin-induced hypoglycaemia was examined. Before salicylate treatment, seven Type II diabetics had brisk increases (mean +/- SEM) in circulating adrenaline (time 0 = 50 +/- 7 pg/ml; peak = 1630 +/- 330 pg/ml), noradrenaline (time 0 = 260 +/- 46 pg/ml; peak = 770 +/- 140 pg/ml), glucagon (time 0 = 38 +/- 6 pg/ml; peak = 75 +/- 10 pg/ml) and pancreatic polypeptide (time 0 = 149 +/- 30 pg/ml; peak = 1170 +/- 180 pg/ml) in response to insulin-induced hypoglycaemia. In contrast to previous studies in normal subjects, treatment with sodium salicylate failed to augment hypoglycaemia-induced secretion of adrenaline, noradrenaline or pancreatic polypeptide in Type II diabetics. The glucagon response to hypoglycaemia was augmented by sodium salicylate when the data were expressed as the incremental area under the glucagon vs. time curve, but not when peak response was used for analysis. These results are inconsistent with a prostaglandin-related generalized defect in glucose recognition in Type II diabetics and suggest that augmentation of hormone secretion in these patients by sodium salicylate may be specific for glucose-induced insulin secretion.

Diabetes Mellitus, Type 2↗

PubMed1984

Lack of a direct alpha-adrenergic effect of epinephrine on glucose production in human subjects.

To determine whether alpha-adrenergic stimulation can directly increase glucose production in humans, we infused epinephrine plus propranolol in six normal subjects. The contribution of pancreatic islet effects was eliminated by the infusion of somatostatin. Despite high levels of epinephrine (1,234 +/- 255 pg/ml; mean +/- SE), plasma glucose fell from 85 + 1 to 71 +/- 7 mg/dl. Glucose production rate fell from 1.88 +/- 0.06 to 1.50 +/- 0.16 mg X kg-1 X min-1. During control studies in the same subjects (propranolol and somatostatin without epinephrine), plasma glucose fell from 87 +/- 1 to 75 +/- 3 mg/dl and glucose production fell from 1.93 +/- 0.10 to 1.58 +/- 0.13 mg X kg-1 X min-1. Thus, under conditions of suppressed insulin and falling glucose levels, both of which favor a positive response, a high level of alpha-adrenergic stimulation failed to directly increase glucose production. To ensure that the liver was not refractory to other stimuli, glucagon was administered during infusion of epinephrine and propranolol. In these studies, plasma glucose rose to 175 +/- 20 mg/dl and glucose production plateaued at 3.71 +/- 0.30 mg X kg-1 X min-1 (n = 7). These findings were similar to the effects of propranolol, somatostatin, and glucagon without epinephrine on plasma glucose (196 +/- 15 mg/dl) and glucose production (3.65 +/- 0.29 mg X kg-1 X min-1). Thus, although the liver remained responsive to glucagon during alpha-adrenergic stimulation, no alpha-adrenergic augmentation of glucose production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Adaptation of B and A cell function during prolonged glucose infusion in human subjects.

States of insulin resistance are characterized by hyperinsulinemia that often appears to be out of proportion to the minimal degree of hyperglycemia. One possible explanation for these findings is that mild hyperglycemia per se can cause an adaptive increase in islet sensitivity to glucose, leading to increased insulin output at a given glucose level. To test this hypothesis, we compared acute insulin responses (AIR) and acute glucagon responses (AGR) to 5-g arginine injections before and after 20-h glucose infusions (200 mg X m-2 X min-1) in 11 healthy men of varying age and degree of adiposity. The 20-h glucose infusion caused an increase in fasting plasma glucose (PG) in all subjects (95 +/- 2 vs. 130 +/- 3 mg/dl). PG was clamped at three levels (approximately 95, 165, and 235 mg/dl) before and after the 20-h glucose infusion. Despite matching of PG levels, consistent increases of AIR were observed after the 20-h glucose infusion: 86 +/- 10 vs. 57 +/- 8 at PG = 95 (P = 0.002); 241 +/- 20 vs. 192 +/- 22 at PG = 165 (P = 0.02); and 508 +/- 59 vs. 380 +/- 50 microU/ml at PG = 235 mg/dl (P = 0.009). In addition, the slope of the relationship between AIR and PG level (potentiation slope), a measure of B cell sensitivity to glucose, increased consistently from 2.28 +/- 0.35 (control) to 3.07 +/- 0.45 (P = 0.004) after the 20-h infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Islet function and stress hyperglycemia: plasma glucose and epinephrine interaction.

Catecholamines and a number of other hormones released during stress states contribute to the development of hyperglycemia by directly stimulating glucose production and interfering with tissue disposal of glucose. However, hyperglycemia stimulates the secretion of insulin and inhibits the secretion of glucagon, effects that will diminish the degree of hyperglycemia resulting from direct actions of stress hormones on glucose production and disposal. The key additional role of catecholamines in the development of stress hyperglycemia is interference with the normal feedback control of insulin and glucagon secretion by circulating glucose levels. Although pancreatic islet responses to hyperglycemia may be modulated by catecholamines, any increase of insulin secretion or suppression of glucagon secretion that does occur may be important for limiting the degree of elevation of circulating glucose that results. Thus, plasma insulin and glucagon levels during stress states will reflect the interaction between the opposing effects of hyperglycemia and catecholamines. Diabetic patients who have impaired islet responses to glucose will be particularly prone to the development of marked hyperglycemia during stress states because they may be unable to respond to the influence of hyperglycemia in counteracting adrenergic inhibition of insulin secretion and stimulation of glucagon secretion.

Animals↗

PubMed1984

Evidence for noncholinergic ganglionic neural stimulation of B cell secretion.

Insulin levels increase after 2-deoxyglucose (2DG) administration in dogs. This observation is in contrast to the decrease in insulin level post-2DG in baboons and rabbits. To evaluate a possible neural mechanism mediating this increase in insulin level, we studied normal mongrel dogs with 2DG alone, 2DG during ganglionic blockade, beta-adrenergic blockade, and postganglionic parasympathetic blockade. There was an increase in plasma epinephrine, norepinephrine, pancreatic polypeptide, insulin, and glucose post-2DG alone. During ganglionic blockade, the increase in epinephrine, norepinephrine, and pancreatic polypeptide post-2DG was completely abolished, verifying ganglionic blockade of sympathetic and parasympathetic pathways, respectively. Despite this, ganglionic blockade failed to abolish the insulin rise after 2DG. Postganglionic parasympathetic blockade did not change the insulin rise after 2DG. However, beta-adrenergic blockade completely abolished the insulin rise after 2DG. The above data suggests that 1) the insulin rise post-2DG is beta-adrenergic but 2) the ganglionic neurotransmitter mediating the 2DG-induced insulin rise during ganglionic blockade is noncholinergic (possibly peptidergic).

Animals↗

PubMed1984

Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men.

To determine whether islet adaptation during insulin resistance involves increased responsiveness to the level of plasma glucose, insulin resistance was induced in nine normal men by giving dexamethasone (Dex) (3 mg twice daily for 2 days). Plasma insulin and acute insulin responses (AIR) to isoproterenol were measured at three different glucose levels under control and Dex conditions. During Dex there were elevations above control levels of basal glucose (104 +/- 2 vs. 94 +/- 3 mg/dl) and insulin (21 +/- 3 vs. 13 +/- 2 microU/ml, both P less than 0.03). When glucose levels were raised stepwise by matching amounts using glucose clamps, AIR to isoproterenol rose as a linear function of glucose level under both conditions but rose more steeply during Dex. That is, the potentiating effect of glucose (delta AIR/delta glucose) was greater during Dex: 1.3 +/- 0.2 vs. 0.8 +/- 0.2 (P less than 0.01). Similarly, matched increments in glucose level produced greater increments in prestimulus insulin level during Dex (P less than 0.03). We conclude that 48 h of Dex raises the "gain" of the potentiating effect of glucose. Because the direct effect of glucocorticoids on B cell function has been reported to be inhibitory, the observed stimulation is likely to be a result of the insulin resistance caused by Dex.

Adaptation, Physiological↗

PubMed1984

Pentobarbital anesthesia suppresses basal and 2-deoxy-D-glucose-stimulated plasma catecholamines.

Since pentobarbital anesthesia is known to attenuate certain autonomic reflexes, we tested whether pentobarbital would suppress both basal and stimulated levels of plasma catecholamines and whether a large stimulus might counterbalance this suspected suppression. In untrained dogs, sampled by venipuncture, pentobarbital (30 mg/kg iv) decreased the plasma concentration of epinephrine (E) from 146 +/- 9 to 38 +/- 8 (SE) pg/ml (n = 46) and norepinephrine (NE) from 276 +/- 13 to 91 +/- 10 pg/ml (both P less than 0.0005), suggesting that barbiturate anesthesia suppresses sympathetic outflow in these mildly stressed animals. Pentobarbital also had a marked suppressive effect on the lower baseline catecholamines (E, 84 +/- 14 pg/ml; NE, 118 +/- 10 pg/ml; n = 6) of trained, chronically catheterized dogs, suggesting that it was capable of suppressing resting sympathetic outflow as well. To determine whether pentobarbital anesthesia also suppressed reflex activation of the sympathetic nervous system, the plasma catecholamine response to the neuroglucopenic agent, 2-deoxy-D-glucose (2-DG), was measured in conscious and in pentobarbital-anesthetized dogs. In conscious dogs, the administration of 2-DG (100 mg/kg iv) doubled the base-line plasma concentration of E and NE 30 min after the 2-DG injection. In contrast, the administration of 2-DG (100 mg/kg iv) to pentobarbital-anesthetized dogs produced no significant increase of either plasma catecholamine, suggesting marked suppression of this sympathetic reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

PubMed1984

Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.

In order to assess whether patients with noninsulin-dependent diabetes mellitus (NIDDM) possess normal insulin secretory capacity, maximal B cell responsiveness to the potentiating effects of glucose was estimated in eight untreated patients with NIDDM and in eight nondiabetic controls. The acute insulin response to 5 g intravenous arginine was measured at five matched plasma glucose levels that ranged from approximately 100-615 mg/dl. The upper asymptote approached by acute insulin responses (AIRmax) and the plasma glucose concentration at half-maximal responsiveness (PG50) were estimated using nonlinear regression to fit a modification of the Michaelis-Menten equation. In addition, glucagon responses to arginine were measured at these same glucose levels to compare maximal A cell suppression by hyperglycemia in diabetics and controls. Insulin responses to arginine were lower in diabetics than in controls at all matched glucose levels (P less than 0.001 at all levels). In addition, estimated AIRmax was much lower in diabetics than in controls (83 +/- 21 vs. 450 +/- 93 microU/ml, P less than 0.01). In contrast, PG50 was similar in diabetics and controls (234 +/- 28 vs. 197 +/- 20 mg/dl, P equals NS) and insulin responses in both groups approached or attained maxima at a glucose level of approximately 460 mg/dl. Acute glucagon responses to arginine in patients with NIDDM were significantly higher than responses in controls at all glucose levels. In addition, although glucagon responses in control subjects reached a minimum at a glucose level of approximately 460 mg/dl, responses in diabetics declined continuously throughout the glucose range and did not reach a minimum. Thus, A cell sensitivity to changes in glucose level may be diminished in patients with NIDDM. In summary, patients with NIDDM possess markedly decreased maximal insulin responsiveness to the potentiating effects of glucose. Such a defect indicates the presence of a reduced B cell secretory capacity and suggests a marked generalized impairment of B cell function in patients with NIDDM.

Adult↗

PubMed1984

Effect of pentobarbital anesthesia on plasma norepinephrine kinetics in dogs.

To assess the effect of barbiturate anesthesia on sympathetic nervous system activity, plasma norepinephrine (NE) kinetics were measured in trained dogs with an indwelling right atrial catheter before and during iv administration of pentobarbital sodium (30 mg/kg, iv, plus continuous infusion at 0.1-0.2 mg/kg X min). Plasma NE levels fell by 64 +/- 6% from 103 +/- 22 to 42 +/- 18 pg/ml (mean +/- SEM; n = 6; P less than 0.001) during pentobarbital anesthesia. As measured with the isotope dilution method using steady state kinetics, basal NE spillover rate into plasma was 203 +/- 92 ng/min; this level fell by 91 +/- 2% (P less than 0.001) to 24 +/- 13 ng/min during anesthesia. Clearance of NE from plasma was also impaired by the anesthesia. Before pentobarbital administration, the NE clearance rate from plasma was 1.7 +/- 0.4 liters/min; this rate fell during anesthesia by 71 +/- 6% (P less than 0.001) to 0.5 +/- 0.2 liters/min. During control studies in which no barbiturate was administered, there was no change in plasma NE levels (111 +/- 11 vs. 116 +/- 19 pg/ml; n = 3), NE spillover rate into plasma (209 +/- 56 vs. 204 +/- 61 ng/min), or clearance of NE from plasma (1.8 +/- 0.4 vs. 1.7 +/- 0.2 liters/min). The marked suppression of the NE spillover rate into plasma during pentobarbital administration suggests that this type of anesthesia causes a profound suppression of baseline sympathetic nervous system activity in trained dogs. The observed fall of plasma NE levels underestimated the degree of suppression of sympathetic nervous activity by the anesthesia, since there was a concurrent fall in NE clearance from plasma.

Anesthesia↗

PubMed1984

Prolonged infusion of somatostatin with glucagon replacement increases plasma glucose and glucose turnover in man.

To determine the effect of isolated beta-cell impairment on glucose turnover, we administered a 46-h infusion of somatostatin (200 micrograms/h) with glucagon replacement (0.75 ng/kg X min) to eight normal men. Fasting plasma insulin levels fell slightly, but significantly, from 8 +/- 2 (+/- SEM; control) to 6 +/- 2 microU/ml 46 h after beginning the infusion (P less than 0.001). Over the same period, fasting plasma glucose rose from 89 +/- 2 to 114 +/- 2 mg/dl (P less than 0.001), and plasma glucagon levels remained unchanged (79 +/- 5 vs. 82 +/- 8 pg/ml P = NS). Glucose turnover was measured by isotope dilution using [3-3H]glucose. The glucose production rate rose consistently from a baseline value of 2.08 +/- 0.04 to 2.45 +/- 0.06 mg/kg X min (P less than 0.01). The glucose disposal rate also rose consistently from 2.11 +/- 0.04 to 2.53 +/- 0.09 mg/kg X min (P less than 0.01). We conclude that prolonged mild selective insulin deficiency produced by infusion of somatostatin with glucagon replacement in normal men causes an elevation of the fasting plasma glucose level, which is maintained by glucose overproduction rather than by glucose underutilization. Overproduction of glucose may also be important in maintaining basal hyperglycemia in patients with noninsulin-dependent diabetes mellitus who have a similar impairment of insulin secretion.

Adolescent↗

PubMed1984

Dose-dependent suppression of norepinephrine appearance rate in plasma by clonidine in man.

Clonidine is an alpha 2-receptor agonist which lowers both blood pressure and plasma norepinephrine (NE) levels in man. To determine whether the clonidine-induced fall in plasma NE is due to decreased NE appearance into plasma or increased NE clearance from plasma, NE infusions [( 3H]NE; 15 microCi/m2 bolus and 0.35 microCi/m2 X min infusion) were performed in 10 normal subjects, aged 25-56 yr. Arterialized plasma samples were obtained for measurements of steady state [3H]NE specific activity and plasma NE to allow calculation of plasma NE appearance rate and NE clearance before and 120-140 min after 1.5 and 5.0 micrograms/kg oral clonidine. Using an identical protocol, responses were compared in 4 subjects after placebo administration. Clonidine produced a dose-related reduction in mean arterial blood pressure, but no significant change in heart rate. The basal supine plasma NE concentration of 204 +/- 21 pg/ml (mean +/- SEM) fell by 27% (P less than 0.02) after low dose clonidine and by 51% (P less than 0.001) after high dose clonidine. There was no change in plasma epinephrine levels. The basal plasma NE appearance rate of 0.25 +/- 0.03 microgram/m2 X min was reduced by 32% (P less than 0.01) after low dose clonidine and by 52% (P less than 0.001) after high dose clonidine. The basal plasma NE clearance of 1.2 +/- 0.08 liters/m2 X min was unchanged after clonidine treatment. There was no change in mean plasma NE levels, plasma NE appearance rate, or mean arterial pressure after placebo administration. These findings demonstrate that the clonidine-induced fall in plasma NE levels is due to a dose-dependent suppression of plasma NE appearance rate and provide evidence for alpha 2-adrenergic inhibition of sympathetic nervous system activity in normotensive subjects.

Adult↗