Biomedical subjects

R C Veith

Publications and source records attributed to R C Veith.

At least 37 records · Page 2Linked to original sources

PubMed1995

Effects of Alzheimer's disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine.

BACKGROUND: The resting cerebrospinal fluid (CSF) norepinephrine concentration is unchanged or even increased in patients with Alzheimer's disease (AD). These in vivo findings appear to be inconsistent with the post-mortem locus ceruleus neuronal loss that is reported in patients with AD. METHODS: The effects of AD and advanced age on central nervous system noradrenergic status were estimated by comparing CSF norepinephrine concentrations following the administration of yohimbine hydrochloride, clonidine hydrochloride, and placebo in outpatients with AD and older and young normal subjects. Levels of yohimbine, its metabolite 11-hydroxy-yohimbine, and clonidine were measured in CSF and plasma samples. Behavioral responses were quantified by rating the Tension, Excitement, and Anxiety items on the Brief Psychiatric Rating Scale. RESULTS: Yohimbine-induced increases of CSF norepinephrine concentrations were greater in both patients with AD and normal older subjects than in normal young subjects. Clonidine-induced decreases of CSF norepinephrine concentrations did not differ among groups. Behavioral arousal following the administration of yohimbine was greater in patients with AD than in the other groups. CONCLUSIONS: Central nervous system noradrenergic responsiveness is enhanced in normal older subjects, and this age effect is retained in patients with AD. Behavioral sensitivity to increased central nervous system noradrenergic activity is enhanced in patients with AD.

Adult↗

PubMed1995

Lack of cholinergic regulation of vasopressin and norepinephrine responses to hypertonic saline in humans.

In vitro studies in hypothalamic-pituitary explants in the rat have suggested cholinergic mediation of arginine vasopressin (AVP) osmoregulation. In this study we attempted to demonstrate, in humans, cholinergic mediation of AVP osmoregulation. Specifically, we tested the hypothesis that the plasma AVP response to an osmolar stimulus would be attenuated by pharmacologic blockade of central nervous system muscarinic or nicotinic receptors in humans. We also evaluated the effects of cholinergic blockade on the norepinephrine (NE) response to an osmolar stimulus. Young normal males underwent hypertonic saline infusion following administration of the centrally active muscarinic antagonist scopolamine or the centrally active nicotinic antagonist mecamylamine. Neither mecamylamine nor scopolamine affected the AVP response to hypertonic saline infusion. Mecamylamine reduced NE concentrations in a dose-dependent manner, but did not affect the slope of the NE increase during hypertonic saline infusion. In a second experiment, we evaluated the effects of scopolamine and mecamylamine on the AVP and NE responses to physostigmine, a cholinesterase inhibitor which stimulates AVP release into plasma through a non-osmolar central nervous system cholinergic mechanism. Scopolamine eliminated the AVP response to physostigmine. Mecamylamine reduced NE concentrations both before and after scopolamine administration but did not affect the slope of the AVP response. These results fail to support cholinergic regulation of the AVP response to osmolar stimulation in humans.

Adult↗

PubMed1995

Enhanced hypothalamic-pituitary-adrenocortical axis responses to physostigmine in normal aging.

BACKGROUND: The purpose of this study was to determine the effects of normal human aging on the hypothalamic-pituitary-adrenocortical (HPA) axis response to the centrally active cholinesterase inhibitor physostigmine. This drug stimulates the HPA axis at a suprapituitary level by increasing central nervous system (CNS) cholinergic activity. METHODS: Plasma ACTH, beta-endorphin (beta E) and cortisol responses to a 10-minute infusion of physostigmine (.0125 mg/kg) were compared between groups of 10 normal older subjects (71 +/- 2 years [mean +/- SEM]) and 9 normal young subjects (27 +/- 2 years). Plasma physostigmine concentrations were measured to assess the comparability of the pharmacologic stimulus between groups. RESULTS: Endocrine responses were substantially greater in older subjects than young subjects for ACTH (p < .01), beta E (p < .01) and cortisol (p < .01). Plasma physostigmine concentrations did not differ between older and young subjects. CONCLUSION: This study demonstrated increased HPA axis responsivity to a CNS cholinergic stimulus in normal human aging.

Adrenocorticotropic Hormone↗

PubMed1994

Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra.

The hormone insulin can down-regulate the function and synthesis of the re-uptake transporter for norepinephrine (NET) in vivo and in vitro. In the present study we tested whether this action of insulin is generalized to another member of the catecholamine transporter family. We determined the level of dopamine transporter (DAT) mRNA expression in the ventral tegmental area (VTA)/substantia nigra compacta (SNc) of rats which were chronically treated with vehicle or insulin via the third cerebral ventricle (i.c.v.). DAT mRNA was significantly elevated in the VTA/SNc of rats treated with insulin, as compared with levels in vehicle-treated rats. This is in contrast to our previous observation that i.c.v. insulin decreases NET mRNA in the rat locus coeruleus, and suggests that insulin may have differential and specific modulatory effects on CNS catecholaminergic pathways.

Animals↗

PubMed1994

Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma norepinephrine kinetics.

BACKGROUND: To determine whether elevations of plasma norepinephrine (NE) in major depression represent increased sympathetic nervous system (SNS) activity and to assess the effects of desipramine hydrochloride on sympathetic function. METHODS: SNS activity was assessed in depressed patients and controls by an isotope-dilution, plasma NE kinetic technique using mathematical modeling and compartmental analysis. This approach provided estimates of the rate of NE appearance into an extravascular compartment, which is the site of endogenous NE release from SNS nerves, the corresponding rate of NE appearance into plasma, and the rate of NE clearance from plasma. RESULTS: Norepinephrine appearance into the extravascular and vascular compartments was significantly elevated in 17 depressed patients compared with that in 36 controls. The rate of NE clearance from plasma was similar in both groups. This is compatible with increased SNS activity in major depression. Desipramine, given for 2 days, significantly reduced the concentration of NE in plasma of patients and controls by markedly suppressing the rates of extravascular and vascular NE appearance, compatible with a short-term reduction in SNS activity. Desipramine prolonged the rate of NE clearance from plasma, consistent with a blockade of NE re-uptake into SNS nerve terminals. The initial suppression of SNS activity by desipramine was reversed by long-term (28 days) treatment of patients, with extravascular and vascular NE appearance rates returning to approximately basal levels. An associated rise in plasma NE concentrations compared with the baseline was attributable to a progressive reduction in plasma NE clearance. CONCLUSION: Sympathetic nervous system activity is elevated in major depression and is suppressed by short-term desipramine administration. The demonstration of SNS reactivation occurring with prolonged desipramine treatment is compatible with the theory that long-term treatment desensitizes CNS alpha 2-adrenergic receptors and emphasizes the value of examining the temporal course of responses to pharmacological challenges of neuroendocrine systems. Previously reported elevations of plasma NE during prolonged administration of tricyclic antidepressants are probably the result of a reduction in plasma NE clearance, not an increase in SNS activity.

Adult↗

PubMed1994

Desipramine-induced increase in norepinephrine transporter mRNA is not mediated via alpha 2 receptors.

In situ hybridization for the norepinephrine transporter (NET) was performed in rats receiving short-term (2 days) treatment with either an alpha-2 (alpha 2) receptor agonist (clonidine) or antagonist (yohimbine) followed by saline or desipramine (DMI). The 'saline' group received intraperitoneal injections of either clonidine, yohimbine or saline followed by an injection of saline. The 'DMI' group received intraperitoneal injections of either clonidine, yohimbine or saline followed by an injection of DMI. Dosages given were clonidine (0.10 mg/kg), yohimbine (0.5 mg/kg) and DMI (10 mg/kg). In the 'saline' group, the clonidine/saline animals had significantly less NET mRNA expression compared to the saline/saline animals. In the 'DMI' group an attentuation of the DMI-induced increase in NET mRNA was observed in the clonidine/DMI animals compared to the saline/DMI animals. In both treatment groups, administration of yohimbine did not alter the expression of NET mRNA compared to the appropriate control animals. These findings suggest that the DMI-induced increase in NET mRNA is not mediated via alpha 2 receptors for, although clonidine attenuates DMI's effect, there is no reciprocal enhancement with the alpha 2 antagonist yohimbine. Clonidine's attenuation of DMI's effect may occur via the imidazole receptor as clonidine is an agonist at the imidazole receptor but yohimbine has no known activity at it. Additional studies are needed to clarify the mechanism of the DMI-induced increase in NET mRNA and to correlate changes in NET mRNA with transporter expression at the synaptic membrane.

Animals↗

PubMed1994

Canine liver releases neuropeptide Y during sympathetic nerve stimulation.

To determine whether the liver or gut releases neuropeptide Y (NPY) from their sympathetic nerves, we performed bilateral thoracic sympathetic nerve stimulation (BTSNS) in halothane-anesthetized dogs and calculated gut and liver NPY spillover. BTSNS markedly increased hepatic NPY spillover (delta = +32 +/- 8 ng/min) and arterial NPY concentration (delta = +220 +/- 56 pg/ml), despite no effect on gut NPY spillover (delta = +8 +/- 7 ng/min). To determine the liver's contribution to this increase of circulating NPY, hepatic nerves were selectively stimulated (HNS). Liver NPY spillover increased markedly (delta = +114 +/- 42 ng/min, P < 0.025) during HNS, causing a large increase of arterial NPY (delta = +586 +/- 237 pg/ml, P < 0.025). Using this ratio of liver spillover to arterial increments of NPY, we calculated that the liver makes a major contribution (70%) to circulating NPY levels during BTSNS. The predominant form of canine NPY coeluted with synthetic [Met17]NPY and the minor form of canine NPY coeluted with the oxidized form of [Met17]NPY on high-performance liquid chromatography. We therefore conclude that dog NPY is likely [Met17]NPY and that the liver, rather than the gut, is a major source of circulating NPY during sympathetic nerve stimulation and perhaps stress.

Animals↗

PubMed1993

Autonomic dysfunction in patients with dementia of the Alzheimer type.

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.

Aged↗

PubMed1993

A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training.

A computer simulation of the circulatory system was used to kinetically model secretion, inhibition, and clearance of tissue plasminogen activator (t-PA) during three different processes that increase active t-PA levels: epinephrine infusion, exercise, and endurance training. Infusion of epinephrine stimulated an increase in t-PA secretion that was proportional to the plasma epinephrine concentration. In addition, epinephrine infusion increased hepatic blood flow and t-PA clearance, thus slowing the increase of plasma t-PA levels. During exercise, t-PA levels increased due both to increased t-PA secretion and to decreased clearance secondary to reduced hepatic blood flow. The increase in t-PA secretion during exercise was directly proportional to the epinephrine concentration in blood with the same ratio of t-PA secretion to epinephrine as found during epinephrine infusion, suggesting that increased plasma epinephrine during exercise was the primary stimulus for t-PA secretion. Lastly, the simulation predicted that 6 months of endurance training produced a decrease in resting plasminogen activator inhibitor type 1 (PAI-1) secretion, resulting in less t-PA inhibition and an overall increase in active t-PA after training. Accurate analysis of the regulation of active t-PA levels in blood required simultaneous modeling of t-PA and PAI-1 secretion, hepatic clearance, and inhibition of t-PA by PAI-1.

Computer Simulation↗

PubMed1993

Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects.

To assess the effect of desipramine (DMI) on corticotropin-releasing-factor (CRF) activity in the central nervous system, we measured cerebrospinal fluid (CSF) concentrations of CRF in healthy volunteers following short-term administration of DMI or placebo. DMI administration for 2 days was associated with a significant dose-related reduction in CRF concentrations. There was a nonsignificant 6% reduction in CRF concentrations among the 10 subjects who received 50 mg DMI (delta CRF: -3 +/- 2 pg/ml) and a significant 14% fall in the CRF concentrations of the eight subjects who received 100 mg DMI (delta CRF: -8 +/- 3 pg/ml). The mean CSF concentration of CRF was unchanged in the six subjects randomized to placebo (delta CRF: 1 +/- 5 pg/ml). DMI administration had no effect on CSF norepinephrine concentrations (n = 24) or on plasma cortisol (n = 25). We conclude that short-term administration of DMI in healthy volunteers is associated with a dose-related reduction in CSF concentrations of CRF.

Adult↗

PubMed1993

Hypertonic saline infusion increases plasma norepinephrine concentrations in normal men.

We recently demonstrated in patients with panic disorder that hypertonic saline infusion induces acute panic with the same frequency and intensity as the standard hypertonic sodium lactate infusion. We now report the effects in normal men of hypertonic saline infusion on neuroendocrine systems possibly relevant to panic and anxiety. We administered a 150-min infusion of hypertonic saline (5% sodium chloride) which increased plasma osmolality from 288 +/- 1 to 303 +/- 2 mOsm/kg and produced the appropriate increase of plasma arginine vasopressin (AVP). Plasma norepinephrine (NE) increased substantially during hypertonic saline infusion compared to a normal saline infusion of equal volume and duration. Mean arterial pressure (MAP) also increased and there were significant positive correlations between MAP and NE, but not between MAP and AVP during hypertonic saline infusion. Plasma epinephrine and cortisol did not differ between conditions. Although the pattern of plasma adrenocorticotrophic hormone (ACTH) response differed between hypertonic saline and normal saline conditions, ACTH concentrations did not increase compared to baseline in either condition. These data suggest that hypertonic saline infusion increases sympathetic nervous system activity in normal men.

Adrenocorticotropic Hormone↗

PubMed1993

Evidence for two differentially regulated populations of peripheral beta-endorphin-releasing cells in humans.

In the current study we tested the hypothesis that human plasma beta-endorphin (beta E) is derived from at least two subpopulations of beta E-releasing cells: one sensitive to glucocorticoids as well as to dopamine (DA; regulated analogously to the corticotrophs of the rat pituitary), and one insensitive to glucocorticoids but sensitive to DA (regulated analogously to the melanotrophs of the rat pituitary). To test this hypothesis, human plasma levels of ACTH, cortisol, and beta E-like immunoreactivity were measured at baseline and after haloperidol treatment (0.05 mg/kg, i.v.) in two experimental groups, one pretreated with dexamethasone (1.5 mg) and one pretreated with placebo. Plasma PRL levels were also measured in both groups as an indicator of DA receptor blockade. Dexamethasone partially suppressed both baseline and haloperidol-stimulated levels of human plasma beta E-like immunoreactivity, whereas it completely suppressed both basal and haloperidol-stimulated levels of ACTH and cortisol and had no statistically significant effect on either basal or haloperidol-stimulated PRL levels. These data support a negative feedback effect of glucocorticoids on one DA-sensitive cell population that releases both ACTH and beta E (corticotroph like), but not on a second cell population that releases beta E but not ACTH.

Administration, Oral↗

PubMed1992

Basal sympathoadrenal function in posttraumatic distress disorder.

Research has consistently shown that patients with posttraumatic stress disorder (PTSD) manifest greater changes in heart rate, blood pressure, and plasma epinephrine than controls when exposed to trauma-related laboratory stressors. However, findings are equivocal as to whether PTSD subjects differ from controls on basal, or tonic, measures of autonomic activity. In this study, PTSD patients (n = 11) and asymptomatic controls (n = 11) were compared on measures of basal sympathoadrenal function, including plasma norepinephrine and epinephrine as well as heart rate and blood pressure. Results showed that PTSD patients were not significantly different from control subjects on any measure. Although phasic alterations in autonomic function in PTSD have been consistently found in previous research, this study suggests that tonic sympathetic nervous system activity in PTSD patients may not differ from that of healthy controls.

Adrenal Glands↗

PubMed1992

Fibrinolytic response during exercise and epinephrine infusion in the same subjects.

To determine whether exercise-induced increases in tissue plasminogen activator (t-PA) were related to plasma epinephrine concentration during exercise, 14 healthy men (aged 24 to 62 years) were studied during epinephrine infusions (10, 25 and 50 ng/kg per min) and graded supine bicycle exercise, beginning at 33 W and increasing in 33-W increments until exhaustion. Plasma epinephrine, active and total t-PA, active plasminogen activator inhibitor type 1 (PAI-1) and t-PA/PAI-1 complex concentrations were measured at each exercise and infusion level. During epinephrine infusion, active and total t-PA levels increased linearly with the plasma epinephrine concentration (respective slopes [+/- SEM] of 0.062 +/- 0.003 and 0.076 +/- 0.003 pmol/ng epinephrine). During exercise, t-PA levels did not increase until plasma epinephrine levels increased, after which both active and total t-PA levels again increased linearly with the plasma epinephrine concentration, but at twice the rate observed with epinephrine infusion (0.131 +/- 0.005 and 0.147 +/- 0.005 pmol/ng, respectively). The t-PA level in blood was directly proportional to the plasma epinephrine concentration during both exercise and epinephrine infusion, suggesting that epinephrine release during exercise stimulates t-PA secretion. In these healthy subjects, active plasminogen activator inhibitor type 1 and t-PA/PAI-1 complex levels were low (41 +/- 11 and 21 +/- 5 pmol/liter, respectively) and did not change significantly during exercise or epinephrine infusion. It is concluded that approximately 50% of the increase in t-PA during exercise is due to stimulated release of t-PA by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Corelease of galanin and NE from pancreatic sympathetic nerves during severe hypoglycemia in dogs.

To determine whether norepinephrine (NE) and galanin are coreleased during reflex activation of the sympathetic nervous system by hypoglycemia, we administered insulin to halothane-anesthetized (0.8%) dogs and measured the spillover of NE and galanin-like immunoreactivity (GLIR) into pancreatic venous plasma. Insulin injection produced hypoglycemia [plasma glucose (PG) = 34 +/- 3 mg/dl] but did not activate pancreatic noradrenergic (delta pancreatic NE output = +20 +/- 130 pg/min) or galaninergic nerves (delta GLIR output = +40 +/- 50 fmol/min). To determine whether more severe hypoglycemia would activate these nerves, insulin was administered to dogs infused with somatostatin (SS; 2.5 micrograms/min) to block the counterregulatory increase of glucagon secretion. SS reduced the glucagon response to hypoglycemia by greater than 90%, which allowed PG to decrease to 14 +/- 1 mg/dl. Pancreatic NE output increased by 470 +/- 140 pg/min (P less than 0.005); however, pancreatic GLIR output did not increase significantly (delta = +70 +/- 50 fmol/min). When SS was discontinued, pancreatic NE output increased by 490 +/- 200 pg/min (P less than 0.025), and GLIR output increased by an additional +160 +/- 70 fmol/min (P less than 0.025; total delta from baseline = +230 +/- 90 fmol/min, P less than 0.025), suggesting that SS may restrain pancreatic NE and galanin release. Pancreatic NE and GLIR spillover were also increased during severe hypoglycemia when ganglionic neurotransmission was partially impaired with hexamethonium but not when the neural pathway was interrupted by spinal cord transection. We conclude that NE and galanin are coreleased from pancreatic sympathetic nerves when these nerves are centrally activated during severe hypoglycemia in halothane-anesthetized dogs.

Animals↗

PubMed1992

Alpha 2-adrenergic regulation of galanin and norepinephrine release from canine pancreas.

We found previously that electrical stimulation of the mixed autonomic pancreatic nerves (MPNS) is anesthesized dogs elicits marked and rapid increases of pancreatic output of both norepinephrine (NE) and galanin, and on that basis hypothesized a role for galanin as a sympathetic cotransmitter in the endocrine pancreas. In the present study, direct evidence was sought for the co-release of galanin and NE from canine pancreas by determining whether pancreatic galanin output is subject to modulation by presynaptic alpha 2-adrenergic mechanisms as has been established for NE. During MPNS (8 Hz, 1 ms, 10 mA, 10 min) in anesthesized dogs, both pancreatic NE and galanin outflow were increased with similar temporal patterns during consecutive stimulations. Blockade of presynaptic alpha 2-adrenoceptors with yohimbine increased and stimulation of presynaptic alpha 2-adrenoceptors with clonidine reduced NE and galanin outflow. Over all experiments, pancreatic spillover of galanin was highly correlated with that of NE. It is concluded that presynaptic alpha 2-adrenergic mechanisms modulate not only NE but also pancreatic galanin release, suggesting that galanin is co-released with NE from noradrenergic nerves in the endocrine pancreas.

Adrenergic alpha-Agonists↗

PubMed1992

Neurohypophyseal and pituitary-adrenocortical responses to the alpha 1 agonist methoxamine in humans.

To test the hypothesis that the release of neurohypophyseal peptides into plasma in humans is stimulated by a central nervous system (CNS) alpha 1 adrenergic mechanism, we measured the responses of arginine vasopressin (AVP) and oxytocin (OT) to intravenous methoxamine, an alpha 1 agonist which enters the CNS following peripheral administration. The potential confound of baroreceptor inhibition of AVP release by the pressor effect of methoxamine was addressed by measuring the plasma AVP response to infusion of norepinephrine (NE), an alpha 1 agonist which does not enter the CNS and which produced an equivalent pressor effect. We also assessed the pituitary adrenocortical system responses to methoxamine and norepinephrine infusions by measuring plasma ACTH and cortisol concentrations. In addition, plasma NE and epinephrine were measured. Methoxamine, but not NE, increased plasma AVP compared to placebo infusion. Neither methoxamine nor NE affected plasma OT. The AVP elevation was delayed until more than 60 min after the methoxamine infusion began and the peak AVP level occurred 30 min after cessation of the infusion. In contrast, ACTH and cortisol increased early during methoxamine infusion and ACTH returned to baseline promptly after the infusion ceased. Although it is possible that the AVP response to methoxamine reflected stimulation of AVP release at a CNS level, it is also possible that the AVP increase represented a rebound response to withdrawal of methoxamine.

Adrenal Cortex↗

PubMed1992

Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.

BACKGROUND: Cardiac aging is characterized by a reduced heart rate response to beta-agonist stimulation with isoproterenol, but whether the ejection fraction and other cardiovascular responses are reduced in humans is largely unknown. In addition, whether reduced beta-agonist responses can be improved with exercise training has not been determined in humans. METHODS AND RESULTS: Cardiovascular responses to graded isoproterenol infusions (3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15 older (age, 60-82 years) and 17 young (age, 24-32 years) rigorously screened healthy men. Thirteen older and 11 young subjects completed 6 months of endurance training and were retested. At baseline, the older group had reduced responses to isoproterenol for heart rate (+65% older versus +92% young, p less than 0.001), systolic blood pressure (+9% versus +24%, p less than 0.001), diastolic blood pressure (-12% versus -24%, p less than 0.05), ejection fraction (+12 versus +20 ejection fraction units, p less than 0.001), and cardiac output (+70% versus +100%, p less than 0.001). The mean plasma isoproterenol concentrations achieved during the infusions were marginally higher (p = 0.07) in the older group (128 +/- 58, 227 +/- 64, 354 +/- 114, and 700 +/- 125 pg/ml) than in the young (79 +/- 20, 178 +/- 49, 273 +/- 79, and 571 +/- 139 pg/ml). Intensive training increased maximal oxygen consumption by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 ml/kg/min, p less than 0.001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 ml/kg/min, p less than 0.001), but training did not augment any of the cardiovascular responses to isoproterenol in either group. The mean plasma isoproterenol concentrations at the four infusion doses were unchanged after training in both groups. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, blood pressure, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol in healthy men. Altered beta-adrenergic responses probably contribute to the reduced cardiac responses to maximal exercise that also occur with aging. Furthermore, intensive exercise training does not increase cardiac responses to beta-adrenergic stimulation with isoproterenol in either young or older men. The reduced beta-adrenergic response appears to be a primary age-associated change that is not caused by disease or inactivity.

Adult↗