Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat

Acute episodes of severe hypoxia are among the most common stressors in neonates. An understanding of the development of the physiological response to acute hypoxia will help improve clinical interventions. The present study measured ACTH and corticosterone responses to acute, severe hypoxia (8% inspired O(2) for 4 h) in neonatal rats at postnatal days (PD) 2, 5, and 8. Expression of specific hypothalamic, anterior pituitary, and adrenocortical mRNAs was assessed by real-time PCR, and expression of specific proteins in isolated adrenal mitochondria from adrenal zona fascisulata/reticularis was assessed by immunoblot analyses. Oxygen saturation, heart rate, and body temperature were also measured. Exposure to 8% O(2) for as little as 1 h elicited an increase in plasma corticosterone in all age groups studied, with PD2 pups showing the greatest response ( approximately 3 times greater than PD8 pups). Interestingly, the ACTH response to hypoxia was absent in PD2 pups, while plasma ACTH nearly tripled in PD8 pups. Analysis of adrenal mRNA expression revealed a hypoxia-induced increase in Ldlr mRNA at PD2, while both Ldlr and Star mRNA were increased at PD8. Acute hypoxia decreased arterial O(2) saturation (SPo(2)) to approximately 80% and also decreased body temperature by 5-6 degrees C. The hypoxic thermal response may contribute to the ACTH and corticosterone response to decreases in oxygen. The present data describe a developmentally regulated, differential corticosterone response to acute hypoxia, shifting from ACTH independence in early life (PD2) to ACTH dependence less than 1 wk later (PD8).     

Comparison of Corticotrophin and Corticosteroid Response to Lysine Vasopressin,Insulin, and Pyrogen in Man

Plasma corticotrophin (ACTH) and corticosteroid levels in response to lysine vasopressin (LVP), insulin hypoglycaemia, and pyrogen have been compared in seven subjects with normal pituitary adrenal function. Intramuscular vasopressin was a weak stimulus to corticotrophin release, peak values lying within the range 49 to 141 pg/ml. Insulin hypoglycaemia consistently caused a more noticeable increase, with peak levels between 114 and 364 pg/ml, while pyrogen was the most powerful, corticotrophin levels rising to between 209 and 1,725 pg/ml. Peak plasma corticosteroid levels showed less pronounced differences between the three tests, and correlated poorly with peak ACTH levels. Thus, relatively small acute changes in corticotrophin levels produce near-maximal adrenal stimulation. Under these conditions, plasma corticosteroid measurements do not accurately reflect circulating corticotrophin levels. These findings help to explain the physiological basis of several observations on the corticosteroid responses to these clinical test procedures.     

The differential regulation of aldosterone output in hamster adrenal by angiotensinII and adrenocorticotropin.

Aldosterone was isolated from hamster adrenal cells and was identified by high performance liquid chromatography and thermospray mass spectroscopy analysis. Basal outputs from adrenal cell suspensions were of the same order of magnitude, 8.4 ± 1.9 ng and 8.0 ± 0.7 ng/2 h/50,000 cells, for aldosterone and corticosteroid, respectively. The outputs of aldosterone and corticosteroid increased with K⁺ concentrations to reach maxima of 3.3- and 1.6-fold at 10 meq/l of K⁺. Angiotensin_II (A_II) produced dose-dependent increases in aldosterone and corticosteroid outputs with maxima of 3- and 4-fold, respectively. In contrast, ACTH induced relatively no changes in aldosterone output, whereas dose-dependent increases in corticosteroid output were found. In time study experiments, with 10⁻⁸ M A_II, aldosterone and corticosteroid outputs were maximally increased after 1 h (6-fold) and 3 h (1.8-fold), respectively. At 10⁻⁸ M, ACTH had a small stimulatory effect on aldosterone output after 6 h, whereas it provoked a gradual increase in corticosteroid output (up to 7-fold after 8 h of incubation). The effects of A_II and ACTH on adrenal cytochrome P-450_11β involved in the last steps of aldosterone formation were evaluated by c combined in vivo andin vitro experiments. The P-450_11β mRNA level was increased by a low sodium intake but not by a 24 h ACTH stimulus. These results taken together indicate that ACTH and A_II differentially regulate P-450_11β. It is postulated that these two regulatory peptides regulate the hamster adrenal steroidogenesis by different P-450 genes.     

Elevated corticosterone and inhibition of ACTH responses to CRH and ether in the neonatal rat: effect of hypoxia from birth

Hypoxia is a common cause of neonatal morbidity and mortality. We have previously demonstrated a dramatic ACTH-independent activation of adrenal steroidogenesis in hypoxic neonatal rats, leading to increases in circulating corticosterone levels. The purpose of the present study was to determine if this ACTH-independent increase in corticosterone inhibits the ACTH response to acute stimuli. Neonatal rats were exposed to normoxia (control) or hypoxia from birth to 5 or 7 days of age. At the end of the exposure, plasma ACTH and corticosterone were measured before and after either ether vapors were administered for 3 min or CRH (10 microg/kg) was given intraperitoneally. Thyroid function, pituitary pro-opiomelanocortin (POMC) mRNA and ACTH content, and hypothalamic corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), and AVP mRNA were also assessed. Hypoxia led to a significant increase in corticosterone without a large increase in ACTH, confirming previous studies. The ACTH responses to ether or CRH administration were almost completely inhibited in hypoxic pups. Hypoxia did not affect the established regulators of the neonatal hypothalamic-pituitary-adrenal axis, including pituitary POMC or ACTH content, hypothalamic CRH, NPY, or AVP mRNA (parvo- or magnocellular), or thyroid function. We conclude that hypoxia from birth to 5 or 7 days of age leads to an attenuated ACTH response to acute stimuli, most likely due to glucocorticoid negative feedback. The neural and biochemical mechanism of this effect has yet to be elucidated.     

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling. At approximately 138 days of gestation, fetuses were killed, and adrenals were removed for cell culture and analyses of ACTH-R mRNA and protein. After 48 h, adrenocortical cells were stimulated with ACTH for 2 h, and the medium was collected for cortisol measurement. The same cells were incubated overnight with medium or medium containing ACTH or forskolin (FSK), followed by ACTH stimulation (as above) and cortisol and cellular ACTH-R mRNA analyses. HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH-R mRNA and protein levels by over 35%. HPD cells secreted significantly less cortisol than sham cells (3.2 +/- 1.2 vs. 47.3 +/- 11.1 ng.ml(-1).2 h(-1)) after the initial ACTH stimulation. Overnight incubation of HPD cells with ACTH or FSK restored cortisol responses to acute stimulation to levels seen in sham cells initially. ACTH-R mRNA levels in cells isolated from HPD fetuses were decreased by over 60%, whereas overnight incubation with ACTH or FSK increased levels by approximately twofold. Our findings indicate that the absence of the cortisol surge in HPD fetuses is a consequence, at least in part, of decreased ACTH-R expression and adrenal responsiveness.     

Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone,StAR, and PBR

The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 +/- 1.4 ng/ml; n = 12) and ACTH-stimulated (94.0 +/- 9.4 ng/ml; n = 14) corticosterone levels compared with normoxic controls (basal = 8.3 +/- 0.5 ng/ml; n = 11; stimulated = 51.3 +/- 3.8 ng/ml; n = 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 +/- 4 vs. 78 +/- 8 pg/ml) or after (481 +/- 73 vs. 498 +/- 52 pg/ml) porcine ACTH injection (20 microg/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1alpha mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate.     

Hormonal and renal responses to converting enzyme inhibition during maximal exercise

The role of angiotensin II in the hormonal and renal responses to maximal exercise was investigated by using the angiotensin-converting enzyme inhibitor captopril. Nine male subjects performed a standardized maximal treadmill test with and without acute captopril treatment (25 mg orally). At rest, captopril elevated plasma renin activity and lowered aldosterone levels. With maximal exercise, captopril treatment reduced the increase in mean arterial blood pressure by 8 mmHg and the increase in plasma renin activity by 3.0 ng ANG I.ml-1.h-1. The responses of adrenocorticotropin (ACTH), cortisol, and vasopressin to maximal exercise were not altered by captopril treatment. Although aldosterone levels were reduced at rest with captopril, during maximal exercise no difference was noted between treatments. Captopril treatment had no effects on the renal handling of salts or water during exercise. In conclusion, angiotensin II plays a role in the increase in mean blood pressure during maximal exercise in normal subjects but has no effect on the exercise responses of ACTH, vasopressin, and aldosterone or on the renal handling of salts and water.     

The use of the corticotropin-releasing hormone test to monitor the recovery of patients with Cushing's disease or Cushing's syndrome due to an adrenal adenoma after adenomectomy

Six patients with Cushing's disease and three with Cushing's syndrome due to an adrenal adenoma were monitored after their adenomectomy with the corticotropin-releasing hormone test to evaluate the progress of recovery of their pituitary adrenal function. Before surgery the patients with Cushing's disease showed either high, normal or low responses of plasma ACTH and cortisol to 100 micrograms synthetic ovine corticotropin-releasing hormone (CRH) administered intravenously, whereas all three patients with Cushing's syndrome due to an adrenal adenoma showed no response of plasma ACTH or cortisol to CRH. One or two months after surgery, the patients who had Cushing's disease had low levels of basal plasma ACTH and cortisol and their responses to CRH were extremely low. However, the same patients were tested later, it was found that their responses to CRH gradually increased and reached normal ranges approximately within one year after tumor removal, which coincided with the overall improvement in their clinical signs and symptoms due to adrenal insufficiency. In contrast, the recovery of the pituitary adrenal function in patients who had Cushing's syndrome due to an adrenal adenoma was not complete even one year after surgery. Thus the corticotropin-releasing factor test is a useful criteria to evaluate the recovery of the pituitary adrenal function in these patients after surgery, since the responses of plasma ACTH and cortisol to the administered CRH are parallel with the improvements in clinical signs and symptoms due to adrenal insufficiency in patients with Cushing's disease.     

狗在急性低氧后复氧过程中的心脏功能损伤

六条在心脏上装有高精度压力传感器及微型超声测距探头的慢性实验狗,经两个星期的手术恢复期后,于Halothane麻醉下,给予低氧气体吸入,使动脉血氧饱和度从对照时的99.8±0.1％降到60.7-4.4％。低氧时,左心室功能随着动脉血氧饱和度的下降,表现为中度低氧时增强、严重低氧时减弱的变化。复氧时,出现与低氧时不相同的左心室功能异常,如心动过速、严重心律紊乱、后负荷增高、舒张期末室壁厚度显著增加,室壁舒-缩厚度差减小、室壁舒缩的不匀质性以及极低的心肌顺应性等。这些结果表明,在急性低氧后的复氧过程中,左心室功能存在着一种“复氧损伤”。     

Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus).

Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.     

Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus)

Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.     

ACTH secretion and ventilation increase at similar arterial PO2 in conscious rats

To compare the arterial PO2 (PaO2) at which adrenocorticotropic hormone (ACTH) secretion and ventilation are stimulated, conscious rats with chronic femoral arterial catheters were exposed for 50 min to 21, 18, 15, 12, or 9% O2. Decreases in arterial PCO2 (PaCO2) and increases in arterial pH and adrenocortical system activity occurred consistently throughout the exposure period in rats exposed to 9 or 12% O2. In contrast, changes in PaCO2 or pH were only transient or delayed, plasma ACTH did not change, and plasma corticosterone only increased after 20 min in rats exposed to 15 or 18% O2 relative to those breathing 21% O2. Omitting the large blood sample at 20 min for ACTH eliminated the increase in corticosterone in the 15% O2 group. Overall, ACTH increased, and PaCO2 decreased, below PaO2 of approximately 60 Torr. We conclude that ACTH secretion increases at a similar PaO2 as hyperventilation-induced decreases in PaCO2 and thus represents a primary physiological response to acute hypoxia; hemodynamic stimuli may also interact with hypoxia to augment adrenocortical system activity.     

Corticotropin-releasing factor in humans. II. CRF stimulation in patients with diseases of the hypothalamo-pituitary-adrenal axis

A stimulation test with 100 micrograms ovine or human corticotropin-releasing factor (CRF) is a useful diagnostic tool in diseases of the hypothalamo-pituitary-adrenal axis. No serious side effects were observed during the test procedure. The results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome (n = 42). The CRF test was also repeated after transsphenoidal surgery in 25 patients with Cushing's disease. Successfully operated patients exhibit no, blunted or normal adrenocorticotropic hormone (ACTH) responses to CRF (n = 15), whereas patients who did not show remission remained hyperresponsive (n = 10). In patients with autonomous adrenal cortisol secretion, the ACTH response to CRF was suppressed (n = 10). After surgery the ACTH response to CRF can already be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy and another patient under corticoid therapy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or long-term corticoid therapy is due to hypothalamic CRF deficiency. The decrease of the ACTH responses to CRF in glucocorticoid-treated patients correlated directly to the daily corticoid dosage. Since the ACTH hyperresponse to CRF in 6 patients with Cushing's disease was also suppressed by short-term dexamethasone treatment, the pituitary level as target site for the acute feedback inhibition is also demonstrated. The evaluation of the CRF-induced ACTH response in patients with secondary adrenal failure without detectable pathology in the sella and suprasellar region (n = 6) enables the differentiation between hypothalamic and pituitary adrenal insufficiency. In patients with hypothalamic lesions the ACTH response to CRF was normal whereas insulin hypoglycemia failed to induce an ACTH rise.     

Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs.

Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which in turn could cause either pulmonary hypertension or arterial hypoxemia. In experiment 1, rats were given acute or long-term injections of TNF-alpha (recombinant human) in vivo. Rats treated acutely received either saline or TNF-alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20 min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats treated chronically received injections of either saline or TNF-alpha (250 micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9). Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4 g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min; 3% O2) and angiotensin II (ANG II; 0.025-0.40 micrograms). Pulmonary pressor responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In experiment 2, lungs were isolated and perfused and received direct pulmonary arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity was not different between control and TNF-alpha rats before the injections, but TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.     

Altered adrenal gland cholesterol metabolism in the apoE-deficient mouse

Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of esterified cholesterol (EC) at the expense of cholesterol delivery to the steroidogenic pathway. In the present study, parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient (apoe(-/-)) mice. Adrenal gland EC content and the EC/free cholesterol (FC) ratio in mice stressed by adrenocorticotropin (ACTH) treatment or saline injection were reduced in apoe(-/-) compared to apoe(+/+) mice. Relative to apoe(+/+) mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland scavenger receptor class B, type I (SR-BI), LDL receptor, and LDL receptor related protein (LRP) levels and the activities of ACAT or HMG-CoA reductase showed no difference between genotypes. Apoe(-/-) and apoe(+/+) mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.     

ACTH stimulation of adrenal epinephrine and norepinephrine release

Epinephrine (E) and norepinephrine (NE) levels were measured simultaneously in the adrenal veins of 6 patients before and after stimulation with 0.25 mg beta 1-24 ACTH. In 1 patient with Cushing's syndrome, E and NE were also measured before and 30 min after dexamethasone. There was a significant increase in NE and E secretion (p less than 0.002) from both adrenal glands after ACTH stimulation. In the patient with Cushing's syndrome, there was also a slight increase in plasma E levels after dexamethasone. It is postulated that ACTH stimulated NE and E secretion by augmenting blood flow through the adrenals and by induction of tyrosine hydroxylase and dopamine beta-hydroxylase, although a direct effect of ACTH on NE and E secretion cannot be excluded. It is also possible that the increase in adrenal catecholamine secretion after ACTH may be due to ACTH augmentation of catecholamine secretion by endogenous opioids such as beta-endorphin.     

Pressor inhibition of angiotensin-induced ACTH secretion

We investigated whether the pressor effects of systemically administered angiotensin II (AII) influence ACTH secretion. Adrenalectomized barbiturate-anesthetized mongrel dogs with constant low resting cortisol concentrations due to slow constant cortisol infusion received either bolus injections (2.5 micrograms kg-1) or 15-min i.v. infusions of a low dose (12.5 ng kg-1min-1) of AII during which blood samples were taken for ACTH and cortisol determinations. In sequential continuous experiments in each dog, blood pressure was allowed to increase in response to AII administration or was controlled by means of concurrent i.v. injections or infusions of the hypotensive drug papaverine, or by blood withdrawal from the vena cava. When the arterial pressure rise induced by AII was substantially attenuated or prevented by papaverine administration or blood withdrawal, mean ACTH secretion rates increased 400-800% and mean ACTH concentrations increased by 280-500%. On the other hand, AII administration alone caused large increases in mean arterial blood pressure but did not increase ACTH secretion significantly above control levels. These data suggest that when endogenous AII levels are elevated without a concurrent increase in blood pressure, as occurs during hypovolemia or sodium depletion, AII may have a significant influence on ACTH secretion.     

Effect of controlled ventilation on renal and splanchnic blood flows during severe arterial hypoxia

The present study was undertaken to evaluate the extent that the lung inflation reflex attenuates vasoconstrictor responses in renal cortex and splanchnic beds during severe arterial hypoxia. Hypoxia was induced by inspiration of a 3-5% oxygen gas mixture in three groups of chloralose-anesthetized dogs: Group I, free breathing; Group II, controlled ventilation; Group III, free breathing with arterial PCO2 held constant. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In Group I, hypoxia caused marked hyperventilation, which was accompanied by no significant change in VC in renal cortex, and by reductions in VC in spleen (-36%), pancreas (-56%), and duodenum (-28%). In Group II, hypoxia caused reduction in VC in renal cortex (-70%), and reductions in VC in spleen, pancreas, and duodenum similar to those in Group I. In Group III, hypoxia again caused marked hyperventilation, but reductions in VC in renal cortex, spleen, pancreas, and duodenum were similar to those in Group II. Results indicate that during severe arterial hypoxia activation of lung inflation reflex does not attenuate or reverse vasoconstriction in renal cortex, spleen, pancreas, and duodenum.