Tolerance to the humoral and hemodynamic effects of caffeine in man

Acute caffeine in subjects who do not normally ingest methylxanthines leads to increases in blood pressure, heart rate, plasma epinephrine, plasma norepinephrine, plasma renin activity, and urinary catecholamines. Using a double-blind design, the effects of chronic caffeine administration on these same variables were assessed. Near complete tolerance, in terms of both humoral and hemodynamic variables, developed over the first 1-4 d of caffeine. No long-term effects of caffeine on blood pressure, heart rate, plasma renin activity, plasma catecholamines, or urinary catecholamines could be demonstrated. Discontinuation of caffeine ingestion after 7 d of administration did not result in a detectable withdrawal phenomenon relating to any of the variables assessed.     

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.     

Circadian variations of the urinary excretion of catecholamines and electrolytes

Concomitant measurements of circadian variations in the urinary excretion of dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), epinephrine (E) as well as of creatinine, sodium and potassium under controlled dietary conditions during relative physical and emotional rest in 13 volunteers have shown that maximum excretion of all these substances occurred in the afternoon period between 14:30h and 18:00h, and minimum excretion in the morning between 4:00h and 5:00h. The changes were in some cases progressive from one collection period to the other, and synchronized for NE and E. DA and HVA excretions fluctuated from subject to subject. Excretory rhythms of sodium and potassium were found to be similar to those of the catecholamines. This can be explained by diurnal changes in renal blood flow and different renal excretory mechanisms of catecholamines. None of the catecholamines correlated with the urinary volume but urinary NE and E positively correlated with urinary creatinine, urinary NE and E with urinary DA and urinary sodium with urinary E. There are some common patterns in the diurnal rhythms of catecholamines and electrolytes but their interrelationship is different for individual catecholamines.     

The sex-peptide gene (Acp70A) is duplicated in Drosophila subobscura

OBJECTIVE: We quantified the presence of diurnal rhythms in various computerized fetal heart rate parameters in normal pregnancies to assess their clinical relevance. STUDY DESIGN: Modified cosine analysis was applied to the outcomes of computerized analysis of continuous 24-hour fetal heart rate recordings in 26 normal pregnancies. Diurnal rhythms in maternal heart rate and plasma hormones were assessed in 15 and 17 pregnancies, respectively. Correlations between maternal and fetal rhythms were calculated. RESULTS: A significant diurnal rhythm in basal heart rate was present in 73% of the fetuses and was closely related to the maternal heart rate rhythm. Diurnal rhythms in heart rate variability, accelerations, and activity were present in only 30% to 50% of the fetuses. CONCLUSIONS: The mother entrains fetal diurnal rhythms. The normal variability in neural development may account for the absence of diurnal rhythms in some fetuses.     

Rhythms in the central nervous system and 1/f fluctuations of the heart rate

We have developed a system to analyze heart rate variability (HRV) (power spectral array of the HRV) during 24 h ambulatory electrocardiographic monitoring. Several rhythms (circadian and several ultradian rhythms) were observed in the power spectral array of the heart rates and 1/f-like fluctuations in the log-log scaled heart rate power spectrum. The circadian change of the heart rate is closely related to the body temperature rhythm. The 90 min rhythm of HRV during sleep was suspected to be produced by the sleep cycle (REM/NREM) and the lower frequency peak of the HRV was coherent with oscillation in amplitude modulated respiration. These circadian and ultradian rhythm as assessed by heart rate variability exist both in normal subjects and in patients with autonomic failure. The power of the high frequency band decreases in subjects with autonomic failure. The power of low frequency components increases during periodic breathing or Cheyne-Stokes respiration. Log-log scaled analysis of the power spectrum of HRV disclosed that the slope of the HRV is markedly modulated by the range of the frequency applied for the least square regression line analysis. The increased power that might be produced by periodic breathing and decreased power in patients with autonomic failure might strongly modulate the slope of the log-log scaled HRV. It is concluded that the power spectral array of the HRV during 24 h period is useful in the detection of circadian and ultradian rhythm, and log-log scaled power spectra might be useful in the overall integration of the heart rate dynamics produced by the central nervous system. The several rhythm factors that might be produced by the central nervous system might modulate 1/f fluctuations of the HRV.     

Novel protein toxin-based strategy for development of cytotoxic T lymphocyte vaccines

Unexplained episodic hypertension, hypotension, or orthostatic intolerance, tachycardia, anxiety, and flushing in 21 patients were investigated for the possibility of hypovolemia by blood volume and individual plasma catecholamines (including autocrine paracrine-born dopamine), determinations baseline, in response to upright posture and catecholamines only during the episodic blood pressure swings. Blood volume was determined by Cr51 fixed to patients' hemoglobin, free norepinephrine, epinephrine, and dopamine with dopamine sulfate following sulfatase hydrolysis, radioenzymatically. The recumbent mean 27.4+/-3% (SE) blood volume decrease from predicted values accentuating to 33.5+/-4% upright was associated with normal baseline plasma free norepinephrine, epinephrine, dopamine, dopamine sulfate, plasma renin activity, and aldosterone with normal mean postural responses from all patients except a hyperresponsive compared to controls (p < 0.04), plasma renin activity increase from 0.657+/-0.1 to 4.47+/-1.8 ng/mL/hr. During the hypertensive, hypotensive, or tachycardic episodes the moderate increase of free norepinephrine and epinephrine (p < 0.04) (but not free dopamine) contrasted with an increase of dopamine sulfate from 2.5+/-0.9 to clearly pathological values of 16.8+/-8.3 ng/mL (p < 0.0003 on % increase of individual values). We conclude that the normal (but to the degree of hypovolemia inappropriately low orthostatism- and episodes-associated sympathetic arousal) is outpaced by considerable episodic dopamine sulfate surges, reflecting extraneuronal dopamine discharge. Whether this increase contributes to the increased natriuresis directly or by inhibiting aldosterone response to renin-angiotensin, perpetuating hypovolemia, remains to be established.     

Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events

We studied the effects of cigarette smoking, sham smoking and smoking during adrenergic blockade in 10 subjects to determine whether smoking released the sympathetic neurotransmitter norepinephrine, as well as the adrenomedullary hormone epinephrine, and whether smoking-associated hemodynamic and metabolic changes were mediated through adrenergic mechanisms. Smoking-associated increments in mean (+/- S.E.M.) plasma norepinephrine (227 +/- 23 to 324 +/- 39 pg per milliliter, P less than 0.01) and epinephrine (44 +/- to 113 +/- 27 pg per milliliter, P less than 0.05) were demonstrated. Smoking-associated increments in pulse rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio were prevented by adrenergic blockade; increments in plasma growth hormone and cortisol were not. Since significant smoking-associated increments, in pulse rate, blood pressure and blood lactate/pyruvate ratio, preceded measurable increments in plasma catecholamine concentrations, but were adrenergically mediated, these changes should be attributed to norepinephrine released locally from adrenergic axon terminals within the tissues rather than to increments in circulating catecholamines.     

Hormonal and metabolic effects of paraventricular hypothalamic administration of neuropeptide Y during rest and feeding

To investigate the role of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus (PVN) in the regulation of autonomic outflow, hormonal (plasma insulin and catecholamines), metabolic (blood glucose and plasma free fatty acids) and cardiovascular (heart rate and main arterial pressure) indices were measured before, during, and after bilateral infusion of NPY (1.0, 0.2, 0.04 micrograms in 1 microliter synthetic CSF) into the PVN of conscious resting rats. Administration of the highest dose (1.0 microgram/microliter) caused bradycardia and reduced circulating norepinephrine levels without effecting circulating fuels, insulin or epinephrine. In a second experiment, feeding-induced changes in hormonal and metabolic indices were assessed after NPY administration (1.0 microgram/microliter) into the PVN. During and after feeding, NPY enhanced the feeding-induced insulin response (P < 0.01) and attenuated the feeding-induced norepinephrine response (P < 0.05). The results of the present study suggest that stimulation of NPY receptors in the PVN decreases sympathetic activity and increases parasympathetic activity in resting conditions, and that these effects are potentiated during feeding.     

Autonomic regulation during rest and mental load in Gilles de la Tourette syndrome

Cardiovascular and catecholaminergic activity during mental load were studied in patients with Tourette syndrome. Patients and controls performed the Color Word Test, preceded by a baseline period, with continuous measurements of heart rate and blood pressure. Blood samples for assay of plasma catecholamine concentrations were obtained before and during the test. The patients showed higher heart rate and blood pressure during baseline than controls, but no differences regarding plasma catecholamines. The tics corresponded with transient increases in heart rate and blood pressure. Spectral analysis of cardiovascular variability during mental load gave only limited evidence of increased sympathetic activity and no alterations in parasympathetic activity in the patients. Therefore, our findings indicate enhanced cardiovascular activity in the patients but not during mental load. The effects of tics on the cardiovascular parameters illustrate the functional complexity of the autonomic nervous system in Tourette syndrome.     

Ambulatory blood pressure, nocturnal blood pressure reduction and plasma catecholamines

OBJECTIVE AND DESIGN: Controversial data have been reported on plasma catecholamines in hypertensives. Aims of this study were to find whether 24-hour ambulatory blood pressure was correlated with circulating catecholamines and to investigate whether nocturnal blood pressure reduction was associated with baseline plasma catecholamines. Samples for catecholamine determination were obtained in 34 consecutive male subjects after a 30-minute rest and before ambulatory blood pressure monitoring. RESULTS: Hypertensive patients (n = 22; 24-hour blood pressure: 145 +/- 14/94 +/- 6 mm Hg) showed similar norepinephrine and epinephrine levels when compared with normotensives (n = 12; 24-hour blood pressure: 124 +/- 6/81 +/- 6 mm Hg), and higher dopamine values (hypertensives: 64.6 +/- 58; normotensives: 26.2 +/- 31 pg/ml; p < 0.05). A positive correlation was observed between dopamine and diastolic nocturnal blood pressure (p < 0.05) while a negative correlation was found between dopamine and nocturnal diastolic blood pressure reduction (p < 0.025). No significant relationship was observed between both norepinephrine and epinephrine, and 24-hour blood pressures. CONCLUSIONS: Since previous reports have documented malfunctioning of dopaminergic system in hypertension, the higher levels of circulating plasma dopamine found in hypertensive patients in the present study may account for a peripheral compensatory increase. The correlation between dopamine and nocturnal blood pressure fall seems to indicate that the impairment of dopaminergic system may influence the 24-hour blood pressure profile, affecting the nocturnal blood pressure reduction.     

Elevated plasma catecholamines without alteration in cardiovascular responsiveness in young men with borderline hypertension

Plasma catecholamines and cardiovascular responses to upright posture, exogenous noradrenaline (NA), and isoproterenol (IP) were examined in 20 young men with borderline hypertension and in 10 age-matched normotensive volunteers. Resting plasma NA and adrenaline (Ad) levels were higher in the borderline hypertensive patients. Significant correlations were found among plasma NA and mean blood pressure (MBP) or heart rate (HR), and between plasma Ad and HR in all individuals in the supine position. The increases in plasma NA were similar between groups for orthostatic positions. Pressor response to exogenous NA and chronotropic response to exogenous IP were not augmented in borderline hypertensives. A negative correlation was found between plasma NA before infusion and the increases of MBP produced by NA or the increases of HR produced by IP in all the individuals. Our observations suggest that there is hyperactivity of the sympathoadrenal system without enhancement in cardiovascular reactivity to catecholamines in young men with borderline hypertension.     

Basal sympatho-adrenal function in quadriplegic man

Plasma catecholamines (CA) were measured at 15 min intervals over a 4 h time period in 5 supine, chronic, quadriplegic male humans subjects. CA levels fluctuated over time through a wide range, often exhibiting brief bursts of very high CA levels which differed from the slower duration fluctuations seen in normal subjects. Spikes of increased plasma CA often, but not always, correlated with muscle spasms, urination or pain and were often accompanied by appropriate changes in blood pressure and heart rate. When examined over a 4 h period, the subjects' median plasma norepinephrine (NE) levels (305.5 +/- 26.8 pg/ml) were within the normal, age-corrected range while plasma epinephrine (E) levels (210.4 +/- 48.9 pg/ml) were higher than those seen in normal control subjects (89.0 +/- 6.9 pg/ml) tested under similar conditions. Also, plasma NE and E levels in the quadriplegics correlated positively in 3 out of 5 subjects which was similar to the balance in normal subjects. Therefore, resting sympatho-adrenal tone, as indicated by plasma catecholamine levels, in quadriplegics is not decreased, but is either normal or increased. Activation of these systems is probably under the control of local spinal reflexes which appear to be capable of maintaining many of the resting automatic functions of the individual.     

Anesthesia with spinal cord stimulation--II). The effects on the cardiovascular function and the level of the plasma catecholamines

In 78 patients who underwent general anesthesia and surgery with nitrous oxide (50-60%) and SCS, SCS decreased heart rate and blood pressure. Both the skin temperature and the amplitude of plethysmographic wave of a left finger increased with SCS. Among plasma catecholamines, only epinephrine level rose significantly with SCS. These results suggest that in addition to the analgesic action, SCS may have sympathetic blocking action, but not suppressive action on release of epinephrine from adrenal gland.     

Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients

OBJECTIVE: To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). DESIGN AND METHODS: After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges. RESULTS: Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). CONCLUSIONS: The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.     

Distribution of coronal and root caries experience among persons aged 60+ in South Australia

The time course of the effects of intravenous or intracoronary administration of peptide leukotrienes on metabolic parameters and on systemic and coronary hemodynamics was evaluated in 15 patients with normal coronary arteries. Peptide leukotriene C4 (2 nmol given as a bolus intravenous injection) induced an early fall (at 2 min) in mean arterial pressure (P < 0.02) associated with a rise in heart rate (P < 0.001) and in plasma levels of epinephrine (P < 0.05) and norepinephrine (P < 0.005), but without significant changes in coronary blood flow or coronary vascular resistance. Mean arterial pressure, heart rate, norepinephrine, and epinephrine returned to baseline values 10 min after leukotriene C4 administration. In contrast, at 10 min post leukotriene C4, with coronary blood flow and myocardial oxygen consumption unchanged, an increase in coronary vascular resistance (P < 0.05) and in myocardial oxygen extraction (P < 0.01) was observed, which returned to baseline values at 20 min post leukotriene C4. Peptide leukotriene D4 (3 nmol, given in the left coronary artery) induced an early (20 s) and transient fall in mean arterial pressure (P < 0.001) paralleled by a rise in heart rate and plasma levels of epinephrine and norepinephrine, all of which returned to baseline at 10 min. Coronary vascular resistance increased at 10 and 15 min (P < 0.02 and P < 0.05, respectively) and myocardial oxygen extraction at 15 min (P < 0.02). These results suggest that small doses of peptide leukotrienes induce both an early and transient fall in mean arterial pressure associated with secondary sympathoadrenergic activation, and a late increase in small coronary arteriolar resistance.     

Renin, aldosterone and arterial pressure responses to acute beta-adrenergic receptor blockage in hypertensive patients

The effect of acute (intravenous) beta-adrenergic blockade with propranolol or pindolol on arterial pressure (BP), plasma renin activity (PRA), and plasma concentration of aldosterone (PA) was evaluated in 20 essential hypertensive men. BP, PRA and PA were determined during continuous recumbency over-night (8 p.m. to 6 a.m.) every 30 min. Two groups of patients were observed. Patients of group 1 exhibited a characteristic day-night rhythm of PRA with low values before midnight and large increases early in the morning. Conversely, no rhythm and very low PRA values were observed in patients of group II. BP was higher in group II than in group I. In group I following intravenous propranolol or pindolol, BP fell within minutes and levels as well as rhythms of PRA were converted to those of group II without treatment. In group II day-night profiles of PRA and BP remained unchanged. Rhythm and concentration of PA in the two groups were not influenced by either drug. In 4 patients of group I infusion of angiotensin II inhibitor did not lower BP. The observations suggest that in the two groups dissimilarities in rhythms of PRA as well as in BP responses to beta-blockade may reflect differences in neuro-adrenergic tone.     

Comparative evaluation of the structural characteristics of the circadian cardiovascular rhythms of healthy persons and in ischemic heart disease

Certain indices of haemodynamics and ECG have been recorded in a biorhythmological study in 141 patients with ischaemic heart disease and in 26 practically healthy individuals. It was established that both the healthy individuals and the patients with ischaemic heart disease have diurnal rhythms of pulse rate, systolic and diastolic pressure, minute heart volume, R--R QRST, TQ intervals and R and T waves on ECG. The acrophases of diurnal rhythms of these indices in the healthy people are in mutual concordance with maximum figures during the daily and early evening hours. In the healthy the acrophase of T wave is seen during the day, in patient with ischaemic heart disease at night and early in the morning. This points to disorders of the bioelectric processes in the myocardium due to its nutritional changes over the 24 hours.     

Apoptosis in the chick wing bud and the permanence of FGF-2 rescue

The concentrations of plasma epinephrine (E) and norepinephrin (N) measured at rest in bullfrogs (Rana catesbeiana) were 12.0 and 8.2 nmol liter-1 respectively: the ratio of [E]/[N] was 1.33 (+/- SE 0.35). Adrenal glands contained high concentrations of epinephrine (2,923 nmole g wet weight-1) and norepinephrine (6,194), at a ratio of 0.46 (+/- SE 0.04) [E]/[N]. This differs from the measured plasma ratio and endogenous release ratios of about 2 for [E]/[N] reported for other Rana species, although the 95% confidence interval of our plasma ratio (0.97) spans the range of values from 0.36 to 2.3, including the observed plasma ratio of 0.46. Therefore, resting plasma catecholamine levels generally reflect the proportional adrenal content of catecholamines. Plasma epinephrine and norepinephrine concentrations significantly increased after activity to 50.4 and 18.1 nmol liter-1, respectively. The ratio of epinephrine to norepinephrine ([E]/[N]) also increased (but not significantly) to 8.53 (+/- SE 4.23), suggesting a shift away from some adrenal tone at rest to sympathetic nerve dominance with activity. Graded hemorrhage led to further increases in plasma epinephrine concentration and [E]/[N] but not norepinephrine, indicating sympathetic but not adrenal involvement. The in vitro epinephrine sensitivity of vascular beds indicates recruitment of the dorsal aorta vascular beds before the pulmocutaneous vascular bed. The minimum sensitivity of vascular beds to perfused epinephrine (10(4) nmol liter-1) was at higher concentrations than maximal plasma concentrations measured during hemorrhage. The bullfrog is less tolerant of hemorrhage than the cane toad Bufo marinus. The major difference in the catecholamine response of these two species was the massive contribution of adrenal catecholamines with severe hemorrhage in toads, which is absent in bullfrogs. This suggests that the enhanced hemorrhage and dehydration tolerance of toads may in part be the result of their greater adrenal gland development and activity.     

I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives

Moxonidine is an I1-imidazoline receptor agonist that reduces blood pressure in hypertensives. Experimental data suggest that moxonidine inhibits central sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg moxonidine orally on muscle sympathetic nerve activity and heart rate in an open study in 8 healthy volunteers. Furthermore, we studied the effects of 0.4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pressure, 24-hour blood pressure profile, and hormone plasma levels in 25 untreated hypertensives in a double-blind, placebo-controlled study. Moxonidine decreased muscle sympathetic nerve activity in both healthy volunteers (P<0.05 versus baseline) and hypertensives (P<0.02 versus placebo). Plasma norepinephrine also decreased (P<0. 01), whereas plasma epinephrine and renin levels did not change (P=NS). Furthermore, moxonidine decreased systolic (P<0.0001) and diastolic (P<0.001) blood pressure. Heart rate decreased after moxonidine in healthy subjects (P<0.05); in hypertensives, heart rate decreased during the night hours (P<0.05) but not during daytime (P=NS). Plasma levels of LDL, HDL, and total cholesterol were not influenced by the drug (P=NS). Moxonidine decreases systolic and diastolic blood pressure by inhibiting central nervous sympathetic activity. This makes this new drug suitable for the treatment of human hypertension and possibly for other cardiovascular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure.     

Geranylgeranylpyrophosphate, a metabolite of mevalonate, regulates the cell cycle progression and DNA synthesis in human lymphocytes

To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at approximately 75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.