PubMed Health⌕ Search

Biomedical subjects

D J Torpy

Publications and source records attributed to D J Torpy.

51 records · Page 3Linked to original sources
PubMed1996

The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system.

The stress system is controlled by brain nuclei at the hypothalamus and brainstem. These nuclei interact with each other and control the HPA axis and sympathetic nervous systems, respectively. Major inputs to the stress system arise from the cerebral cortex and subcortical systems, the sensory organs and nerves, and the endocrine and immune systems. The major peripheral effectors of the stress system are glucocorticoids and the catecholamines. Pathological hypoactivity of the stress system has been associated with atypical depression, the chronic fatigue/fibromyalgia syndromes and autoimmune inflammatory disease; hyperactivity with melancholic depression and anxiety disorders. The stress system responds in a quantitatively and qualitatively specific fashion to different stressors. A major role of the HPA axis is to restrain the immune system and prevent tissue damage. Reciprocal interactions between the HPA axis and immune system constitutes a new endocrine feedback loop that has given rise to the field of neuroendocrine immunology. Gonadal axis hormones directly, and indirectly via the HPA axis, alter the tone of the immune system and the quality and quantity of the inflammatory responses. Effects of the HPA axis on the gonadal axis are consistent with conservation and redirection of valuable resources towards homeostasis during times of stress. These complex interactions between the HPA axis, immune and the gonadal systems may prove to be fundamental in the genesis and perpetuation of autoimmune disease.

Animals↗
PubMed1996

In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation.

Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. CRH receptors (CRH-R1, R2alpha, R2beta) exhibit a specific tissue distribution. Antalarmin, a novel pyrrolopyrimidine compound, displaced 12SI-oCRH binding in rat pituitary, frontal cortex and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmnin (20 mg/kg body wt.) significantly inhibited CRH-stimulated ACTH release and carageenin-induced subcutaneous inflammation in rats. Antalarmin, or its analogs, hold therapeutic promise in disorders with putative CRH hypersecretion, such as melancholic depression and inflammatory disorders.

Adrenocorticotropic Hormone↗
PubMed1995

A synergistic adrenocorticotropin response to naloxone and vasopressin in normal humans: evidence that naloxone stimulates endogenous corticotropin-releasing hormone.

Naloxone stimulates pituitary-adrenal function by blocking an endogenous inhibitory opioidergic tone which modulates pituitary adrenocorticotropin (ACTH) release. In animals, this action of naloxone is mediated by increased corticotropin-releasing hormone (CRH) secretion, but such a mechanism is disputed in humans. CRH and arginine vasopressin (AVP) are known to have a synergistic effect on ACTH secretion in both humans and animals. In vitro, this synergism is independent of L-type voltage-dependent Ca2+ channel function. The aims of this study were therefore: (i) to determine if the combined administration of naloxone and AVP is synergistic regarding ACTH release; (ii) to assess the effect of nifedipine, which blocks L-type Ca2+ channels, on the ACTH response to combined naloxone/AVP stimulation. Seven healthy volunteers were studied using a placebo-controlled, single-blind protocol. Naloxone (125 micrograms/kg) and/or AVP (10 units) were given in all four possible combinations, and oral nifedipine (20 mg) was also given with naloxone and AVP as an additional test. The mean AUC and the mean peak change in ACTH levels following combined naloxone/AVP administration were both significantly greater than the arithmetic sum of the ACTH responses to naloxone and AVP given on separate occasions (AUC: 1,576.4 +/- 417.9 vs. 567.1 +/- 106.1 pmol.min.l-1, p < 0.002; peak change: 37.9 +/- 14.0 vs. 11.8 +/- 2.0 pmol/l, p < 0.007). Nifedipine reduced the ACTH response to combined naloxone/AVP stimulation by 43% (AUC: 1,576.4 +/- 417.9 vs. 897.0 +/- 186.2; p < 0.05), but it remained greater than the sum of the individual responses (897.0 +/- 186.2 vs. 576.1 +/- 106.1, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Adrenocorticotropin hyperresponse to the corticotropin-releasing hormone-mediated stimulus of naloxone in patients with myotonic dystrophy.

We previously showed that CRH-mediated stimuli, including exogenous CRH, cause ACTH hypersecretion in many myotonic dystrophy (DM) patients. We confirmed this by giving naloxone, a stimulator of endogenous CRH release, to a large number of DM patients and controls. DM patients, first degree relatives, and normal controls received i.v. naloxone at 1400 h, and blood was taken for ACTH (RIA) and cortisol (high pressure liquid chromatography) measurements from 15 min before to 120 min after naloxone treatment. DM patients had basal ACTH levels approximately twice those of controls, and their ACTH responses were 4 times those of controls. In contrast, DM basal cortisol levels were not significantly different from those of relatives and were slightly higher than those of normal subjects. Cortisol responses were similar in the three groups, probably due to attenuation at high levels of adrenocortical stimulation, although some patients with inappropriately low cortisol responses for their level of ACTH stimulation warrant further investigation. Nineteen of the 36 patients whose ACTH responses were greater than 3 SD above the normal mean were classed as hyperresponders. Seven patients, who were tested more than once, had reproducible responses relative to those of the normal subjects. We conclude that ACTH hypersecretion after CRH-mediated stimuli, including naloxone, is an inherent, but variable, feature of DM, caused by expression of the genetic mutation at the anterior pituitary. The mechanism is probably a defect in the intracellular pathway initiated by CRH-receptor interaction as a result of abnormal levels of a cAMP-dependent kinase, DMPK, the product of the gene undergoing mutation in DM.

Adolescent↗
PubMed1995

The effect of desipramine on basal and naloxone-stimulated cortisol secretion in humans: interaction of two drugs acting on noradrenergic control of adrenocorticotropin secretion.

Desipramine (DMI), a tricyclic antidepressant and norepinephrine (NE) reuptake blocker, is reported to induce ACTH and cortisol release acutely in humans, probably by facilitating central NE neurotransmission. Tricyclic antidepressant therapy, including DMI, normalizes the ACTH and cortisol hypersecretion that often accompanies depression. The mechanism of hypothalamic-pituitary-adrenal (HPA) axis inhibition by DMI in humans is unknown. In rats, DMI reduces the activity of the locus ceruleus, a major source of NE innervation of the hypothalamic paraventricular nucleus, the site of CRH neurons. Naloxone induces ACTH and cortisol release in humans through a noradrenergic-mediated mechanism and a probable consequent stimulation of hypothalamic CRH release. To study the interaction of these drugs on NE neurotransmission and, hence, HPA axis activity in humans, we administered DMI alone and with naloxone in a randomized, double blind, placebo-controlled protocol in eight healthy male volunteers. DMI (75 mg, orally) was given 180 min before naloxone (125 micrograms/kg BW, i.v.). Plasma ACTH and cortisol were measured at frequent intervals from 60 min before to 120 min after naloxone treatment. Plasma cortisol levels were 77% higher 180 min after DMI compared to those after placebo treatment (287 +/- 17 vs. 162 +/- 14 nmol/L; P = 0.000005). DMI reduced the naloxone-induced rise in cortisol (P = 0.02), but there was no change in the integrated cortisol response. The increase in basal plasma ACTH levels after DMI treatment did not reach statistical significance. DMI significantly increased systolic blood pressure and heart rate consistent with an effect on the noradrenergic control of the cardiovascular system. In summary, DMI increased basal cortisol levels consistent with facilitation of NE neurotransmission and, hence, hypothalamic CRH release. However, DMI had no enhancing effect on naloxone-induced cortisol release. This contrasts with the synergy observed when non-antidepressant agents that increase NE neurotransmission are given with naloxone to humans. DMI increases glucocorticoid feedback sensitivity in the rat HPA axis after several weeks through up-regulation of central corticosteroid receptors. However, this slowly developing effect is unlikely to occur during these acute studies. The effect of DMI on naloxone-induced cortisol release is consistent with an inhibitory effect on central noradrenergic control of ACTH release, perhaps at the locus ceruleus. This is the first human study to suggest an inhibitory effect of DMI on central noradrenergic control of ACTH release.

Adrenocorticotropic Hormone↗
PubMed1994

Effect of flumazenil on basal and naloxone-stimulated ACTH and cortisol release in humans.

1. Endogenous benzodiazepine receptor ligands are thought to influence the human hypothalamic-pituitary-adrenal (HPA) axis and naloxone, a known stimulator of adrenocorticotropic hormone (ACTH) release, is thought to act via release of hypothalamic corticotropin-releasing hormone. 2. The aim of the present study was to assess the influence of endogenous benzodiazepine-receptor ligands by administering flumazenil (Ro15-1788), a benzodiazepine antagonist, and measuring ACTH and cortisol release, both basal and during naloxone-stimulation. 3. Nine normal volunteers in a placebo-controlled double-blind design were studied. Flumazenil (0.5 mg, i.v. bolus) was given 2 min before naloxone (125 micrograms/kg bodyweight, i.v. bolus) immunoreactive-adrenocorticotropic hormone (IR-ACTH) and cortisol levels were measured at frequent intervals from 60 min before to 120 min after naloxone injection. 4. Flumazenil had no effect on ACTH and cortisol release when given alone; flumazenil area under the ACTH/time curve (pmol/L.min) = -36.5 +/- 63.5 compared with placebo = -53.5 +/- 31.8, flumazenil area under the cortisol/time curve (nmol/L.min x 10(-3)) = - 2.4 +/- 2.4 compared with placebo -0.56 +/- 1.4. Flumazenil did not change the ACTH and cortisol release achieved with naloxone; naloxone area under the ACTH/time curve (pmol/L.min) = 327.8 +/- 61.7 compared with flumazenil/naloxone = 366.3 +/- 88.1, naloxone area under the cortisol/time curve (nmol/L. min x 10(-3) = 12.2 +/- 3.4 compared with naloxone/flumazenil = 10.5 +/- 2.1. 5. The authors conclude that flumazenil dose not modify basal or stimulated ACTH and cortisol release in healthy humans. This would suggest that endogenous benzodiazepine-like ligands and the benzodiazepine/gamma-aminobutyric acid receptor complex do not tonically influence the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗
PubMed1994

Paradoxical inhibition by aspirin of naloxone-induced adrenocorticotropin secretion in myotonic dystrophy.

The ACTH response to endogenous or exogenous CRH is increased in patients with myotonic dystrophy (DM), possibly because of abnormal function of cAMP-dependent protein kinases in this condition. Arachidonic acid (AA) metabolites are believed to interact with the cAMP-dependent second messenger system activated by CRH; therefore, drugs that interfere with AA metabolism may alter ACTH secretion in DM. In this study, seven DM patients were given naloxone, which stimulates endogenous CRH release, and aspirin, which inhibits the synthesis of prostaglandins from AA via the cyclooxygenase metabolic pathway. Pretreatment with aspirin reduced the mean integrated ACTH response to naloxone by 33% (P < 0.05). However, the corresponding 18% reduction in cortisol levels was not statistically significant (P > 0.10). These findings are in contrast to those of a previous study using an identical protocol, in which aspirin increased the ACTH response to naloxone in six normal volunteers. This difference between DM and control subjects is consistent with the hypothesis that the interaction between AA metabolites and the cAMP-dependent protein kinase-A second messenger system is abnormal in the corticotrophs of persons with DM.

Adrenocorticotropic Hormone↗
PubMed1994

Alprazolam attenuates vasopressin-stimulated adrenocorticotropin and cortisol release: evidence for synergy between vasopressin and corticotropin-releasing hormone in humans.

Alprazolam (APZ), a triazolobenzodiazepine with unique clinical utility, has potent inhibitory effects on the human hypothalamic-pituitary-adrenal axis. Because APZ inhibits CRH secretion from isolated rat hypothalami and inhibits the probable CRH-mediated effect of naloxone on ACTH release, it is likely APZ acts as an inhibitor of hypothalamic CRH release in humans. The two principal physiological ACTH secretagogues are CRH and arginine vasopressin (AVP). We studied the ACTH and cortisol responses to an ACTH-releasing dose of AVP with and without preadministration of APZ in humans. Our hypothesis was that acute CRH deprivation by APZ would attenuate the ACTH response to vasopressin, as CRH and AVP act synergistically to control ACTH release. This synergy may depend on activation of subpopulations of corticotropes, some of which require both CRH and AVP together to elicit an ACTH response and/or intracellular "cross-talk" between second messenger pathways stimulated by the secretagogues. APZ (2 mg, orally) was given to eight healthy volunteers 90 min before AVP (0.0143 IU/kg BW, iv) in a randomized, double blind, placebo-controlled design during afternoon studies. ACTH and cortisol levels were measured at frequent intervals from 60 min before to 120 min after AVP injection. APZ reduced the mean integrated ACTH and cortisol responses to AVP by 67% and 70% respectively [ACTH, 161.6 +/- 59.7 vs. 53.0 +/- 20.9 pmol/min.L (P = 0.022); cortisol, 9314 +/- 3310 vs. 2763 +/- 1472 nmol/min.L (P = 0.020, AVP vs. APZ/AVP, respectively)]. APZ reduced the mean peak ACTH and cortisol responses to AVP by 57% (P = 0.023) and 40% (P = 0.0012), respectively. AVP levels were not significantly different in those who received APZ or placebo. This study provides further evidence of the potent inhibitory effects of APZ on ACTH and cortisol release in humans and is the first to find that APZ inhibits AVP-stimulated ACTH and cortisol release. This study also suggests that CRH/AVP synergy is an important physiological mechanism for ACTH release in humans, as indicated by the blunted ACTH response to AVP after APZ-mediated acute CRH deprivation. Inhibition of the pituitary-adrenal axis by APZ may explain its unique efficacy in psychiatric disorders thought to be associated with dysregulation of hypothalamic CRH release.

Adrenocorticotropic Hormone↗
PubMed1993

Naloxone stimulation of ACTH secretion during petrosal sinus sampling in Cushing's syndrome.

1. Petrosal sinus sampling has been used to establish the source of adrenocorticotropin (ACTH) in ACTH-dependent Cushing's syndrome. Naloxone, an opioid antagonist, stimulates ACTH secretion, probably via release of endogenous hypothalamic corticotropin releasing hormone (CRH). 2. Three patients with hypercortisolism were studied. Two showed suppressed (> 50%) urinary-free cortisol excretion with high-dose dexamethasone treatment (2 mg every 6 h for 2 days), one did not suppress. The patients were subjected to bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with simultaneous peripheral venous (forearm) samples. Basal (unstimulated) samples were taken and naloxone (125 micrograms/kg bodyweight) was given intravenously with subsequent simultaneous sampling. Plasma ACTH was measured by radio-immunoassay (RIA). 3. All cases exhibited a marked rise in immunoreactive (IR)-ACTH levels (pmol/L) after naloxone injection, basal to peak: case 1, left 11.5-22.1, right 9.8 with no rise, peripheral 9.1-9.5; case 2, left 456-863, right 125-501, peripheral 59-82; case 3, left 12.7-13.0, right 277-431, peripheral 12.1-11.7. All results indicate pituitary Cushing's syndrome, with a central to peripheral ratio > 2.3:1. Pituitary Cushing's syndrome was confirmed on the results of trans-sphenoidal pituitary surgery in cases 1 and 3. 4. It is suggested that naloxone injection during petrosal sinus sampling in Cushing's syndrome may assist in the diagnosis of ACTH source, by enhancing ACTH release from a pituitary micro-adenoma.

Adrenocorticotropic Hormone↗
PubMed1993

Alprazolam blocks the naloxone-stimulated hypothalamo-pituitary-adrenal axis in man.

Alprazolam (APZ) is a benzodiazepine with unique antidepressant activity for a drug of its class. There is some evidence of inhibition of the unstimulated hypothalamo-pituitary-adrenal axis by APZ which may be important in its therapeutic action, and could be detrimental in APZ-treated subjects who encounter stressful stimuli. To assess the effect of APZ on stimulated ACTH and cortisol secretion, we studied 14 normal subjects in a randomized, double-blind, placebo-controlled design. APZ or placebo capsule was administered orally in doses of 0.5 mg and 2 mg, 90 min before either naloxone, 125 micrograms/kg body weight i.v. bolus dose, a known stimulator of ACTH and cortisol release, or placebo. After naloxone stimulation, the area under the plasma ACTH/time curves was significantly reduced by APZ, in both the 2 mg (P < 0.0005) and 0.5 mg (P < 0.005) doses, compared to their respective placebo studies; similar reductions in area under the plasma cortisol/time curves occurred after 2 mg (P < 0.00002) and 0.5 mg (P < 0.0005) APZ doses. We conclude that APZ is a potent inhibitor of naloxone-stimulated ACTH and cortisol release in humans. Since APZ has been shown to inhibit CRH release in vitro, and naloxone-induced ACTH secretion is likely to be caused through CRH release, this suggests that APZ inhibition of naloxone action is via the parvocellular CRH neurons of the paraventricular nucleus and/or central neurotransmitter pathways impinging directly or indirectly on these CRH neurons. Thus APZ may exert at least some of its clinical effects through inhibition of central CRH release. APZ treatment could lead to a relative hyporesponse of the pituitary-adrenal axis during stress. APZ may be an important tool for manipulation of hypothalamic CRH release in studies of pituitary-adrenal function.

Adrenal Glands↗
PubMedDate not supplied

Effect of sodium valproate on naloxone-stimulated ACTH and cortisol release in humans.

1. Gamma-aminobutyric acid (GABA) and endogenous opioids each inhibit hypothalamic CRH secretion. In humans, the opioid antagonist, naloxone, stimulates the release of CRH, and so of ACTH and cortisol, while alprazolam, an indirect GABAA agonist, blocks naloxone-induced ACTH and cortisol secretion. Sodium valproate (SV) inhibits ACTH release in response to CRH, metyrapone and substance P. We hypothesized that, if this action is GABAA-mediated, SV should also inhibit naloxone-stimulated ACTH release. 2. We studied five healthy volunteers in randomized, double-blind, placebo-controlled afternoon studies with SV 400 mg, given 180 min before i.v. naloxone 125 micrograms/kg bodyweight. Plasma concentrations of ACTH, cortisol and SV were measured at intervals during the experiments. 3. SV had no effect on the mean integrated ACTH and cortisol responses to naloxone; ACTH: 165 +/- 21 versus 284 +/- 40 pmol.min per L, P = 0.08; cortisol: 10.5 +/- 1.9 versus 12.8 +/- 1.2 nmol.min per L-3, P = 0.14, placebo/nal versus SV/nal respectively. Basal ACTH and cortisol levels were also not significantly altered by SV (P > 0.30). Mean SV levels were not significantly different between SV/nal and SV/placebo studies (P > 0.50). 4. In conclusion, SV had no effect on naloxone-induced ACTH and cortisol release in normal humans at the dose and plasma drug concentrations studied. This contrasts with the potent inhibitory effect of alprazolam, and suggests that the effect of SV on the human hypothalamic-pituitary-adrenal axis may not be through a GABAA-mediated mechanism. Alternatively, higher plasma SV levels or more sustained exposure to SV may be necessary to inhibit hypothalamic secretion of CRH.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

New diagnostic tests for Cushing's syndrome: uses of naloxone, vasopressin and alprazolam.

1. We set out to investigate whether the administration of naloxone alone, naloxone plus vasopressin (AVP) or naloxone plus alprazolam to patients with Cushing's syndrome would result in a blunted dynamic response of the pituitary-adrenal axis compared with normal volunteers. Cushing's syndrome is often difficult to diagnose. It would be helpful if new tests were available to help in the biochemical distinction between Cushing's syndrome and non-Cushing's syndrome patients. 2. Naloxone testing correctly distinguished all seven patients with Cushing's syndrome (four pituitary Cushing's, two adrenal adenomas, one ectopic ACTH) from normal. Six patients were distinguished by the per cent change of plasma ACTH from basal being less than the normal range of 10 volunteers. The seventh patient (a pituitary Cushing's) was distinguished by the per cent change from basal of plasma cortisol being less than the normal range. 3. Naloxone plus AVP testing of two of four patients with pituitary Cushing's showed a smaller per cent change for both ACTH and cortisol compared with five normal volunteers, correctly distinguishing Cushing's from the normals. 4. Naloxone plus alprazolam did not distinguish Cushing's from normal. 5. Naloxone testing and naloxone plus AVP testing appear to be promising methods of distinguishing Cushing's syndrome from normal. Further experience with these tests, especially with obese and pseudo-Cushing's individuals, will be necessary to determine their place in the diagnosis and differential diagnosis of the cause of Cushing's syndrome.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Pituitary-adrenal responses to combined oral D-fenfluramine and intravenous naloxone in humans.

1. 1. Fenfluramine is an optically active 5-hydroxytryptamine (5-HT) releaser and re-uptake inhibitor. Increased brain 5-HT mediates appetite suppression, the D enantiomer being more active than L- or DL-fenfluramine. Fenfluramine also stimulates the hypothalamic-pituitary-adrenal (HPA) axis, leading to suggestions that this could act as a marker for its biological actions. However, the D enantiomer appears less active than a comparable DL racemate dose in animals, while effects of D-fenfluramine on the human HPA axis remain unproven. The aim of the present study was to clarify this. 2. Seven healthy human volunteers (three male, four female; 18-58 years) received 30 mg oral D-fenfluramine or placebo, followed by 125 micrograms/kg, i.v. naloxone or placebo, in randomized, double-blinded, placebo-controlled afternoon studies. We measured plasma adrenocorticotropic hormone (ACTH) and cortisol levels in samples taken at intervals throughout the study period. 3. In contrast to previous results with DL-fenfluramine, we found no dynamic responses to D-fenfluramine alone and no augmentation of responses to naloxone. 4. Central pathways to HPA axis activation are apparently not stimulated by D-fenfluramine at this dose in humans, in contrast with DL-fenfluramine, where the L enantiomer may be more selective for proposed corticotropin-releasing hormone-mediated, post-synaptic 5-HT2 or noradrenergic mechanisms. As previously reported, D-fenfluramine significantly blunted the circadian fall in basal plasma cortisol, providing in vivo evidence for serotonergic involvement in circadian regulation.

Adolescent↗
PubMedDate not supplied

Urocortin and inflammation: confounding effects of hypotension on measures of inflammation.

Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension.

Animals↗