Comparison of canine corticosteroid responses to mean and phasic increases in ACTH

To determine the dynamics and magnitudes of adrenal corticosteroid responses to ACTH, we measured arterial plasma ACTH and corticosteroid concentrations in conscious dogs during infusions of ACTH or saline. Synthetic alpha 1-24-ACTH was infused at rates of 300,900, or 4,500 ng/30 min either as constant infusions or as three equal short infusions at 10-min intervals. In dogs infused with saline, plasma ACTH fluctuated, whereas corticosteroids did not, suggesting that ACTH is secreted episodically in dogs as in man. The magnitudes of the plasma corticosteroid responses to ACTH infusions were linearly related to the logarithm of the total amount of ACTH infused in 30 min and not to the pattern of administration. In all ACTH infusion experiments, the lag between an increase in arterial ACTH and corticosteroids was not less than 3 min. Mean ACTH half-disappearance time, metabolic clearance rate, and volume of distribution estimated from the different experiments ranged between 1.8 and 2.1 min, 24 and 38 ml . kg-1 . min-1, and 95 and 114 ml/kg, respectively. Collectively, these results explain the apparent paradox that corticosteroid responses to ACTH-releasing stimuli can be initiated before a detectable increase in ACTH above the highest control value (Wood et al. Apparent dissociation of ACTH and corticosteroid responses to ml/kg hemorrhage in conscious dogs. Endocrinology In press).     

Atrial natriuretic peptide response to physical exercise is inhibited by an antagonist of the opioid receptors

It was been shown that physical exercise increases plasma atrial natriuretic peptide (ANP) level. This effect was attributed to the hemodynamic changes of exercise which could increase atrial volume and result in ANP secretion. On the other hand, it was evidenced that morphine and opiate peptides greatly stimulate ANP release. To evaluate to what extent the endogenous opioid secretion during exercise induces the ANP release, six healthy volunteers male trained subjects were submitted to two maximal exercise tests with and without (placebo) opiate receptors blockade by naltrexone (50 mg per os). Blood samples were drawn before (rest) and after maximal exercise in order to measure by radioimmunological methods human atrial natriuretic peptide (alpha-h-ANP), beta-endorphin, plasma aldosterone (ALD), plasma renin activity (PRA) and corticotrophin (ACTH). Expired gas was collected during exercise to measure oxygen consumption. Subjects reached the same value of maximal oxygen consumption (VO2 max) at the end of exercise whatever treatment. Plasma ANP level at rest decreases slightly after administration of naltrexone (32.8 +/- 6.3 pg/ml with placebo versus 21.3 +/- 4.6 pg/ml with naltrexone) but the response to physical exercise was significantly reduced by naltrexone (73.3 +/- 14.9 pg/ml with placebo versus 46.9 +/- 8.6 pg/ml with naltrexone) (p less than 0.05). There was no statistical difference according to the treatment between the plasma levels of beta-endorphin, PRA and ACTH at rest as well as at the end of a maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women

Elevated plasma prolactin and mild hypocortisolemia have been observed in patients with rheumatic disorders. This study was designed to assess the potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary-adrenocortical function. Hypoglycemia was induced by intravenous insulin injection (0.1 IU/kg) in 10 female volunteers of fertile age during their follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo administration. Blood samples were collected from an indwelling catheter inserted into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine and glucose were measured in plasma. Domperidone administration significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14 +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol, norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and 139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/- 62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at 30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine responses to hypoglycemia was similar in both groups. We observed mild norepinephrine response to hypoglycemia but this was irrespective of the medication. In conclusion, pharmacologically-induced hyperprolactinemia did not induce significant changes of hypothalamic-pituitary-adrenocortical function and did not influence sympathoadrenal activity in healthy young women.     

Secretion of Anterior Pituitary Hormones in Man: Effects of Ethyl Alcohol

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radio-immunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113–270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 pm., p < 0.01). This increase was not seen after alcohol ingestion (p < 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 us, 106 ng/5ml, p < 0.01 and 74 us, 121 ng/ml, p < 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, we suggest that ethanol exerts these effects on a suprapituitary site.     

Secretion of anterior pituitary hormones in man: effects of ethyl alcohol.

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5 g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radioimmunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113-270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 p.m., p less than 0.01). This increase was not seen after alcohol ingestion (p less than 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 vs. 106 ng/ml, p less than 0.01 and 74 vs. 121 ng/ml, p less than 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, WE SUggest that ethanol exerts these effects on a suprapituitary site.     

Hormonal and hemodynamic responses to vena caval obstruction in fetal sheep

To test the hypothesis that ACTH and vasopressin responses are quantifiable as functions of induced changes in central venous or arterial pressures, we produced various degrees of vena caval obstruction in fetal sheep (118--134 days gestation). In seven experiments, vena caval obstruction increased heart rate 18 +/- 7 beats/min and carotid arterial oxygen saturation 8.4 +/- 2.1%, but did not alter any measured vascular pressure or hormones. More severe vena caval obstruction (n = 10) decreased mean arterial pressure 13 +/- 2 mmHg, central venous pressure 1.3 +/- 0.3 mmHg, and heart rate 47 +/- 12 beats/min, and increased fetal plasma ACTH 1,047 +/- 448 pg/ml, cortisol 4.4 +/- 2.2 ng/ml, and vasopressin 47.9 +/- 24.2 pg/ml, but did not alter 11-deoxycortisol. The stimulus increased plasma cortisol (radioimmunoassay after chromatography) 100% and "corticosteroids" (radiotransinassay without chromatography) 20%, demonstrating the nonlinear relationship between these two variables. End-inflation plasma ACTH and vasopressin concentrations were significantly related to the induced decreases in mean arterial and central venous pressures, suggesting that the hormonal responses to vena caval obstruction were mediated by cardiovascular mechanoreceptors. Plasma vasopressin concentrations were linearly related to plasma ACTH concentrations (4 = 0.94; P less than 0.001), suggesting parallel release of the two hormones.     

Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion.

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.     

Pancreatic α Cell Function in the Fetal Foal During Late Gestation

Plasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term (approximately 335 days). Fetal alpha cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal alpha cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal pre-infusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper- or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic alpha cells are functional in utero but that they are unresponsive to variations in glycaemia until after birth.     

Increase in plasma ACTH induced by urethane is not a consequence of hyperosmolality

Although anesthetic doses of urethane increase plasma levels of ACTH, the exact mechanism through which this occurs is unclear. We theorized that these increases might be a consequence of an increased systemic osmolality owing to the large doses of urethane usually employed. To evaluate this possibility, we measured plasma osmolality and ACTH in a total of six rats after graded infusions of urethane (N = 3 rats) or equimolar amounts of mannitol (N = 3 rats). Rats received infusions at 15 min intervals up to a cumulative dose equivalent to an anesthetic dose for urethane (1.4 g/kg). Blood samples (0.35 ml) were withdrawn at baseline and 10 min after each infusion. Urethane and mannitol produced significant and equivalent increases in plasma osmolality. However, only urethane evoked increases in plasma ACTH which were maximal (252 ± 55 pg/ml from a baseline of 27 ± 7 pg/ml) after a cumulative dose of 1 g/kg. Thus, increases in plasma ACTH seen after anesthetic doses of urethane are unlikely to be a consequence of its effect on plasma osmolality.     

Central control of peripheral circulating somatostatin in dogs: effect of 2-deoxyglucose

Circulating plasma somatostatin concentrations are known to fluctuate in response to nutrients and hormones. However, little is known about neural or central nervous system (CNS) control of somatostatin secretion. To test whether peripheral circulating somatostatin is influenced by a central stimulus, 2-deoxyglucose (37.5 mg/kg) was infused into a lateral cerebral ventricle of six conscious dogs over a period of 15 min. Plasma somatostatin levels rose from a base line of 105 +/- 6 pg/ml (mean +/- SE) to a peak of 154 +/- 10 pg/ml (P less than 0.005) at 30 min after the onset of the infusion. Somatostatin levels were still significantly elevated (P less than 0.025) at 60 min (119 +/- 6 pg/ml) and thereafter gradually returned toward base line. Plasma glucose and glucagon levels increased in response to intraventricular 2-deoxyglucose. Glucose concentrations rose from 105 +/- 5 mg/dl to peak at 203 +/- 16 mg/dl (P less than 0.005) at 80 min and remained elevated to 120 min. The concentration of plasma glucagon increased from 41 +/- 6 to 92 +/- 18 pg/ml at 60 min (P less than 0.05) and then declined. In marked contrast to intraventricular 2-deoxyglucose, similar concentrations of 2-deoxyglucose administered intravenously (n = 4) resulted in a slight fall in plasma somatostatin. Intraventricular saline did not result in a change in plasma somatostatin. It is concluded that peripheral circulating somatostatin may be susceptible to central nervous system control.     

Effect of brief maximal exercise on circulating levels of interleukin-12

Interleukin-12 (IL-12) is a cytokine that was originally identified as natural killer cell stimulatory factor. It induces the activity of T-helper 1 (Th1) cells and exhibits strong anti-tumor activity. In this study, we studied the effects of brief anaerobic maximal exercise on circulating levels of IL-12. Six healthy males [mean (SD) 25.2 (2.6) years] performed a modified Wingate test exercise (resistance 0.075 kg/kg of body mass). The exercise consisted of five bouts of maximal cycling for 10 s, with rest intervals of 50 s between them. Blood samples were taken before, immediately after, 30 min after, 60 min after and 120 min after the exercise. Plasma concentrations of IL-12 were measured using an enzyme-linked immunosorbent assay. Data were corrected for hemoglobin and hematocrit measurements. Plasma concentrations of IL-12 averaged [mean (SD)] 234.2 (40.9) pg/ml before, 305.2 (62.1) pg/ml immediately after, 202.8 (24.2) pg/ml 30 min after, 239.7 (35.1) pg/ml 60 min after, and 199.6 (49.2) pg/ml 120 min after the exercise. We showed that plasma concentrations of IL-12 increased significantly immediately after brief anaerobic maximal cycle ergometer exercise (P < 0.01). Accepted: 29 October 1999     

Inflammatory response to acute myocardial infarction complicated by cardiogenic shock

We report a case of a 60-year-old man with acute myocardial infarction (AMI) treated using thrombolysis, and complicated by cardiogenic shock (CS). Plasma interleukin (IL) 1 beta, IL 6, IL 8, tumor necrosis factor alpha (TNF alpha), and soluble adhesion molecule (sICAM 1, sE-selectin) levels were measured at 3-h intervals. This observation showed the effect of AMI and CS on the plasma interleukin levels. Remarkable changes were found in the plasma TNF alpha level, which reached two significant peaks. The peak of the first elevation caused by AMI (80.11 pg/ml, vs. normal value 4.35 pg/ml, SD 21.3 pg/ml) was seen 6 h after the onset of the symptoms. After the period of significant decrease, TNF alpha level was increasing until the end of the observation period because of CS (the last TNF alpha level was 204.1 pg/ml). The plasma IL 1 beta level was continually increased during the period of observation (maximal IL 1 beta level 32.1 pg/ml, normal value < 10 pg/ml). The plasma IL 6 level reached the first peak caused by AMI nine hours after the onset of the symptoms (362.85 pg/ml, normal value (10 pg/ml). Because of CS, after the short period of decrease, the plasma IL 6 level was increasing until the end of the observation period (the last IL 6 level was 859.61 pg/ml). The plasma IL 8 level was also elevated throughout the time of observation (max. value 1652 pg/ml, vs. normal value < 30 pg/ml). The soluble adhesion molecule levels (sE-selectin and sICAM 1) were elevated throughout the period of observation without any significant peak.     

Effect of ACTH on the aldosterone response to potassium in sheep with adrenal transplants.

The importance of physiological ACTH stimulation in maintaining the response of aldosterone secretion to potassium was studied in 5 conscious sheep with cervical adrenal autotransplants. Endogenous ACTH secretion was suppressed by dexamethasone. Constant local infusions of potassium that raised adrenal venous plasma by 2 mmol/l increased aldosterone secretion from 3 +/- 1 ng/min (mean +/- SE) to levels of 50 +/- 13 ng/min at 30 min, after which secretion fell to 14 +/- 6 ng/min at 230 min. Addition of submaximal ACTH (0.04 - 0.10 mU/min) to potassium infusions produced similar responses at 0--130 min, but aldosterone secretion increased at 130--190 min and was more sustained (40 +/- 9 ng/min at 230 min; P less than 0.05). Infusions of submaximal ACTH alone did not significantly increase aldosterone secretion above basal levels. Infusions of maximal ACTH (16.6 mU/min) produced higher aldosterone secretion in the group given ACTH replacement. These results show that the aldosterone response to potassium is phasic and poorly sustained in the absence of ACTH. Responsiveness can be restored by doses of ACTH insufficient alone to stimulate aldosterone secretion.     

Ontogeny of endocrine (ACTH, vasopressin, cortisol) responses to hypotension in lamb fetuses

We studied the ACTH, vasopressin (AVP), and cortisol responses to nitroprusside-induced hypotension in 27 chronically cannulated lamb fetuses between 0.53 and 0.98 gestation. Age-related differences in the hormonal responses to hypotension were found. Hypotension was associated with peak AVP levels of 7.8 +/- 2.7 pg/ml (mean +/- SE) in animals less than 0.68 gestation and 63.5 +/- 20 pg/ml in animals 0.89-0.98 gestation (P less than 0.05). The peak ACTH response was 95 +/- 20 pg/ml in the youngest animals and 380 +/- 111 pg/ml in animals 0.83-0.88 gestation (P less than 0.05). These observations suggest that maturation of the systems (possibly neuroendocrine) subserving the hormonal responses occurs in utero. Fetal plasma cortisol levels did not increase in response to the increase in ACTH except in animals 0.89-0.98 gestation. At this time, the basal plasma cortisol levels were high (58.8 +/- 16.8 pg/ml) and the ACTH response to hypotension was attenuated. Taken together, these findings suggest functional negative feedback regulation of ACTH by cortisol in the late gestation fetus.     

Pulsatile secretion of ACTH, GH, LH and TSH in man.

Blood samples were taken every 4 min for 80 min from 5 healthy subjects. Plasma ACTH, GH, LH and TSH were estimated by radioimmunoassays. The mean peak intervals were 11, 12, 13 and 14 minutes respectively and mean peak amplitudes were 25 pg, 1.1 ng, 11 ng and 5.3 muU. Mean durations of ascending and descending limbs of the plasma patterns of these hormones were also measured. The timing of the different hormone peaks appeared to be independent.     

Concomitant increase in plasma atrial natriuretic peptide and cyclic GMP during volume loading

Summary To investigate the effects of fluid expansion on endogenous atrial natriuretic peptide (ANP) and cyclic 3,5-guanosine monophosphate (cGMP), four male volunteers were studied before, during and after intravasal volume loading. Volume expansion was performed by intravenous infusion of 2,000 ml isotonic saline solution within 30 min. Mean plasma ANP levels increased 2.5-fold from 31.2 pg/ml to 81.7 pg/ml 40 min after the start of infusion. Plasma cGMP levels paralleled the rise in ANP, shwoing a mean cGMP increment from 2.7 pmol/ml to a maximum of 8.2 pmol/ml. Both ANP and cGMP levels were back to basal levels 120 min after termination of the infusion. Stimulation of endogenous ANP release by volume loading suggests that ANP is involved in the regulation of fluid homeostasis in man. The parallel rise in plasma cGMP levels supports the idea that cGMP is a mediator for the effects of ANP.Abbreviations ANP atrial natriuretic peptid - cGMP cyclic 3,5-guanosine monophosphate - PRA plasma renin activity     

The effect of trimetazidine on C-reactive protein, cytokines and adhesion molecules in the course of acute myocardial infarction

The aim of this randomised, double-blind, placebo controlled, parallel group study was to assess the effect of trimetazidine (TMZ), a potent antiischaemic drug, on plasma C-reactive protein (C-RP), cytokine and adhesion molecule levels. The study population consists of 18 patients (16 males, 2 females, average age 56.45 +/- 10.97 years) with acute myocardial infarction admitted within 6 hours after onset of symptoms and treated with streptokinase. Blood samples were taken at 3-hour intervals during the time of treatment. All patients were randomised blindly using a centralised randomisation process, between trimetazidine (40 mg bolus i.v. then 60 mg per day for 48 hours intravenously in glucose infusion) or placebo group. Plasma C-RP level was significantly lower in TMZ group (39.5 mg/ml +/- 9.7 mg/ml) as compared to placebo (75.7 +/- 29.4 mg/ml, p < or = 0.001) and peaked 28 hours later in TMZ group. Plasma interleukin 6 (IL 6) level showed a sharp peak 9 hours after the onset of the symptoms in TMZ group (116.9 +/- 180.2 pg/ml vs. 45.4 +/- 37.9 pg/ml) and was increased up to 30 hours after the onset of the symptoms. Plasma interleukin 1 beta (IL 1 beta) was also higher in TMZ group notably 21 hours after the onset of symptoms (26.4 +/- 9.3 pg/ml vs. 16.2 +/- 2.4 pg/ml). TMZ group showed lower plasma E-selectin levels. Plasma IL 8, TNF alpha and ICAM 1 levels were without statistical significant differences. The present study demonstrates a significant reduction of plasma C-reactive protein level in the course of acute myocardial infarction treated with streptokinase and intravenous trimetazidine infusion compared with the group of patients without trimetazidine treatment.     

Pulsatile Secretion of ACTH,GH, LH and TSH in Man

Blood samples were taken every 4 min for 80 min from 5 healthy subjects. Plasma ACTH, GH, LH and TSH were estimated by radioimmunoassays. The mean peak intervals were11, 12, 13 and 14 minutes respectively and mean peak amplitudes were 25 pg, 1.1 ng, 11 ng and 5.3 μU. Mean durations of ascending and descending limbs of the plasma patterns of these hormones were also measured. The timing of the different hormone peaks appeared to be independent.     

Renin-angiotensin-aldosterone system of the normothermic marmot.

Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species.     

Concentration effect relationships of infused histamine in normal volunteers

Histamine was infused in six normal volunteers at rates of 16, 32, 64 and 96 ng/kg/min increasing at 5-min intervals followed by 128 ng/kg/min for 45 min. Heart rate increased, diastolic blood pressure decreased and skin temperature increased in a dose-dependent fashion. Mean heart rate increased by 15.6±5.7 beats/min, mean diastolic pressure fell by 8.8±3.2 mmHg and mean skin temperature increased by 1.2±0.3°C at the highest infusion rate. Mean plasma histamine rose from a basal level of 0.20±0.03 ng/ml to 1.97±0.25 ng/ml at the end of the highest infusion rate. The threshold infusion rate for physiological effects was 64–96 ng/kg/min corresponding to 0.77–0.97 ng/ml. Salivary flow was stimulated by 21% after 30 min at the highest dose infusion (P=0.05). Plasma adrenaline increased 132% but plasma noradrenaline was unchanged.There was a linear decline in heart rate after terminating the histamine infusion with a half time of 82 sec. The half life of infused histamine in the plasma was 102 sec. The clearance of histamine from the plasma was 6.1±0.2 l/min or 83 ml/kg/min.These concentration effect relationships in normals throw doubt on some of the high endogenous plasma histamine values in the literature.