Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the possibility that angiotensin II (ANGII) augments the sensitivity of the pituitary to corticotropin releasing factor (CRF) by comparing, in patients with essential hypertension, the responses of plasma adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and renin activity to a bolus injection of either 0.5 or 1.0 microgram/kg of synthetic ovine CRF in control conditions and after chronic treatment with the converting enzyme inhibitor captopril to block the formation of ANGII; the effects of CRF were examined up to 4 h after its administration. In control studies, we found that the two doses of CRF induced similar increments in ACTH and cortisol, the levels of which remained elevated throughout the studies; these changes were associated with increments in plasma aldosterone that were dose dependent, less pronounced, and of shorter duration and with a slight decrease in plasma renin activity. Captopril treatment increased basal plasma renin activity and lowered plasma aldosterone while leaving basal ACTH and cortisol unchanged. During converting enzyme inhibition, the responses of ACTH and cortisol to CRF were similar to those observed in control studies, whereas the changes in plasma aldosterone and plasma renin activity were, respectively, smaller and greater. From these results, it appears that during ANGII blockade the sensitivity of ACTH to CRF stimulation is unaffected, whereas that of the adrenals to ACTH is selectively reduced at the level of the zona glomerulosa.
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PMID:Effects of angiotensin II blockade on the responses of the pituitary-adrenal axis to corticotropin-releasing factor in humans. 248 58

The effects of ovine corticotropin releasing factor (o-CRF) on plasma aldosterone, 18-OH-corticosterone (18-OHB), plasma adrenocorticotropin (ACTH) and cortisol were determined in eight patients with primary aldosteronism, six with aldosterone-producing adenoma (APA) and two with idiopathic hyperaldosteronism (IHA). The results were compared with those in six normal subjects and eleven patients with essential hypertension (EHT, 5 with low renin and 6 with normal renin). In patients with APA, the peak plasma aldosterone and 18-OHB responses to 100 micrograms iv of o-CRF (226% and 113% increase from baseline, respectively) were greater than those in EHT and normal subjects. The net integrated aldosterone and 18-OHB responses (840 +/- 156, and 419 +/- 121 ng/dl.hr, respectively) were also significantly greater (p less than 0.01) in APA than those in normals and EHT. In two patients with IHA, both the peak and net integrated aldosterone response were smaller than those in APA, in spite of nearly identical plasma ACTH and cortisol responses. These results suggest that augmented responses of mineralocorticoids to o-CRF may be characteristic of aldosteronism due to APA, mediated by CRF-induced ACTH, and possibly other proopiomelanocortin (POMC)-derived peptides.
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PMID:Effects of corticotropin-releasing factor (CRF) on aldosterone and 18-hydroxycorticosterone in essential hypertension and primary aldosteronism. 283 82

Ovine corticotropin releasing factor (CRF) was administered to six normal men and the plasma ACTH and cortisol responses compared with those following the same dose of CRF (200 micrograms) plus the opiate receptor blocker naloxone (20mg). The addition of naloxone was associated with a significant increase in plasma ACTH, cortisol and aldosterone responses. No change was observed in peripheral plasma levels of epinephrine, norepinephrine, arginine vasopressin, angiotensin II or renin activity in response to CRF plus naloxone. It is concluded that endogenous opioid peptides may inhibit the ACTH response to CRF. However the addition of naloxone does not increase the ACTH response to CRF sufficiently to constitute a useful test of pituitary function.
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PMID:Effect of naloxone on the hormone response to CRF in normal man. 299 21

In this study we investigated in the rat the binding and corticotropin-releasing factor (CRF) activity of various constituents of the renin-angiotensin system and the possible angiotensin II receptor changes following procedures known to alter plasma renin activity. We investigated also the CRF activity of angiotensin II in vitro and in vivo in humans. The CRF activity of peptides was studied by their ability to stimulate ACTH release from pituitary cells. Deleting amino acids from the N-terminus of angiotensin II resulted in decreased CRF activity; while the ED50 for angiotensin II was 2 nM, it increased to about 10 nM for the (2-8)-heptapeptide. Angiotensin I had a weak CRF activity, whereas the substrate angiotensinogen had no stimulatory effect even at a concentration of 100 nM. There was a strong correlation between the activation and binding properties of all peptides tested. Dietary salt load or depletion as well as dexamethasone treatment did not affect the number nor the affinity of pituitary angiotensin II receptors. Angiotensin II had a CRF activity on human pituitary cells in vitro. However, peripherally injected agiotensin II at a pressive dose of 7 ng/kg/min did not produce any ACTH release in normal male volunteers. These data suggest that angiotensin II may play a modulatory role in the physiological regulation of ACTH secretion, but this role might be attributed to the endogenous brain angiotensin II as it is not closely dependent on the angiotensin II plasma levels.
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PMID:Corticotropin-releasing activity of the renin-angiotensin system peptides in rat and in man. 300 61

The 41-residue ovine corticotropin-releasing factor (CRF) was administered iv to five normal men. A significant rise in plasma corticotropin (ACTH), cortisol, and aldosterone was demonstrated after a dose of 200 micrograms. There was no demonstrable change in supine blood pressure, pulse rate, plasma vasopressin, renin, catecholamines, insulin, glucagon, or glucose. It is concluded that 200 micrograms ovine CRF stimulates ACTH and cortisol secretion independently of any change in peripheral plasma levels of vasopressin and catecholamines. The cortisol and ACTH responses to ovine CRF were less marked but more prolonged than those after insulin-induced hypoglycemia. The relatively small increment in plasma ACTH, which was well within the physiological range, was associated with a significant increase in plasma aldosterone. Posterior pituitary function was not affected by this dose of ovine CRF.
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PMID:The effect of ovine corticotropin-releasing factor on catecholamine, vasopressin, and aldosterone secretion in normal man. 631 53

The efferent mechanisms by which central administration of corticotropin-releasing factor (CRF) elevates mean arterial pressure and heart rate were assessed in unanesthetized, unrestrained rats. CRF increased blood pressure and heart rate by stimulating noradrenergic sympathetic nervous outflow. CRF-induced cardiovascular changes were not dependent on anterior pituitary hormone release, adrenomedullary epinephrine secretion, the renin-angiotensin system or circulating vasopressin.
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PMID:Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate. 633 66

The behavioral and neuroendocrine reactivity to a novel environment (open field) and the adrenocorticotropic hormone (ACTH)/corticosterone response to a corticotropin-releasing factor (CRF) challenge were measured in 2-mo-old rats from four inbred strains derived from the Wistar-Kyoto rat: spontaneously hypertensive rats (SHRs), hypertensive and behaviorally hyperactive to novelty; WKY, neither hypertensive nor hyperactive; WKHA, hyperactive but normotensive; and WKHT, only hypertensive. The ACTH response to CRF was much lower in SHRs than WKYs, this reduced reactivity being clearly associated with the hyperactivity trait, since it was present in the WKHA and absent in the WKHT strain. On the other hand, the ACTH/corticosterone response to a psychological stimulus (open field) could not clearly discriminate the four strains. The largest difference was found in the prolactin response. Post-open-field levels were much lower in the WKHA (27.11 +/- 4.69 ng/ml) than in the parent WKY strain (83.65 +/- 6.84 ng/ml), the hypertensive strains having intermediate levels (WKHT: 58.05 +/- 7.65 ng/ml; SHR: 64.13 +/- 7.19 ng/ml). Other differences were also found in the levels of aldosterone and renin activity. These results indicate that these strains are an excellent model to study neuroendocrine correlates of hypertension and hyperactivity, which are associated in the SHR strain and may be of interest for the study of the association between neuroendocrine and behavioral characteristics.
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PMID:Psychoneuroendocrine profile associated with hypertension or hyperactivity in spontaneously hypertensive rats. 828 70

1. The paraventricular hypothalamic nucleus (PVH) is a complex structure with both neuroendocrine and autonomic functions. It is a major source of vasopressin and the primary source of corticotropin-releasing factor. In addition, parvicellular PVH neurons have reciprocal connections with brainstem autonomic centres and directly innervate sympathetic preganglionic neurons. Evidence is reviewed which indicates that in conscious rats PVH activation increases blood pressure, heart rate, renal nerve activity and plasma renin activity. 2. In conscious rats, a non-hypotensive haemorrhage (13 mL/kg blood loss over 24 min) results in increased numbers of Fos-immunoreactive cell nuclei within both magnocellular and parvicellular PVH neurons, including the ventral medial parvicellular regions known to contain neuronal projections to brainstem autonomic centres and spinal cord sympathetic preganglionic neurons. 3. Cell-selective ibotenate lesions of the parvicellular PVH significantly blunt the corticosterone response but do not alter blood pressure, heart rate or plasma renin concentration response to non-hypotensive or hypotensive haemorrhage. This and earlier studies indicate that, while the PVH is necessary for the corticosterone response and contributes to increased vasopressin release during blood loss, it does not play an important role in the sympathetic nervous system and renin-angiotensin responses to hypovolaemia and hypotension. 4. There is evidence to indicate that the parvicellular PVH serves as a necessary relay for cardiovascular and renin responses to certain behavioural stressors. We propose that cardiovascular information relayed to parvicellular PVH autonomic regions may be used to modulate behavioural, rather than homeostatic, effects on haemodynamics and renin release.
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PMID:Role of the hypothalamic paraventricular nucleus in cardiovascular regulation. 881 46

The 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) stimulates hypothalamic neurons to increase the secretion of several hormones. This study addressed two questions: 1) are the neuroendocrine effects of DOI mediated via activation of 5-HT(2A) receptors; and 2) which neurons are activated by 5-HT(2A) receptors. The 5-HT(2A) antagonist (+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907; 0.001, 0.01, or 0.1 mg/kg, s.c.) was administered before rats were challenged with DOI (2.5 mg/kg, i.p.). MDL 100,907 produced a dose-dependent inhibition (ED(50) congruent with 0.001 mg/kg) of the effect of DOI on plasma levels of ACTH, corticosterone, oxytocin, prolactin, and renin without altering basal hormone levels. Complete blockade of the effect of DOI was achieved for all hormones at MDL 100,907 doses of 0.01-0.1 mg/kg. In a parallel experiment, DOI was injected 2 hr before killing to determine its effects on the expression of Fos, the product of the immediate early gene c-fos. DOI induced an increase in Fos immunoreactivity in corticotropin-releasing factor (CRF) and in oxytocin-expressing neurons but not in vasopressin-containing neurons in the hypothalamic paraventricular nucleus or CRF cells in the amygdala. Pretreatment with MDL 100,907 (0.1 mg/kg, s.c.) blocked the DOI-induced increase in Fos expression in all regions including the hypothalamus, amygdala (central and corticomedial), bed nucleus of the stria terminalis, and prefrontal cortical regions. The combined neuroanatomical and pharmacological observations suggest that the neuroendocrine responses to DOI are mediated by activation of neurons in the hypothalamic paraventricular nucleus and associated circuitry. Furthermore, selective activation of 5-HT(2A) receptors mediates the hormonal and Fos-inducing effects of DOI.
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PMID:5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells. 1133 86

Exposure to hostile conditions initiates responses organized to enhance the probability of survival. These coordinated responses, known as stress responses, are composed of alterations in behavior, autonomic function and the secretion of multiple hormones. The activation of the renin-angiotensin system and the hypothalamic-pituitary-adrenocortical axis plays a pivotal role in the stress response. Neuroendocrine components activated by stressors include the increased secretion of epinephrine and norepinephrine from the sympathetic nervous system and adrenal medulla, the release of corticotropin-releasing factor (CRF) and vasopressin from parvicellular neurons into the portal circulation, and seconds later, the secretion of pituitary adrenocorticotropin (ACTH), leading to secretion of glucocorticoids by the adrenal gland. Corticotropin-releasing factor coordinates the endocrine, autonomic, behavioral and immune responses to stress and also acts as a neurotransmitter or neuromodulator in the amygdala, dorsal raphe nucleus, hippocampus and locus coeruleus, to integrate brain multi-system responses to stress. This review discussed the role of classical mediators of the stress response, such as corticotropin-releasing factor, vasopressin, serotonin (5-hydroxytryptamine or 5-HT) and catecholamines. Also discussed are the roles of other neuropeptides/neuromodulators involved in the stress response that have previously received little attention, such as substance P, vasoactive intestinal polypeptide, neuropeptide Y and cholecystokinin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABA(A), histamine and serotonin receptors have been used to attenuate the neuroendocrine response to stressors. The neuroendocrine information for these drugs is still incomplete; however, they are a new class of potential antidepressant and anxiolytic drugs that offer new therapeutic approaches to treating anxiety disorders. The studies described in this review suggest that multiple brain mechanisms are responsible for the regulation of each hormone and that not all hormones are regulated by the same neural circuits. In particular, the renin-angiotensin system seems to be regulated by different brain mechanisms than the hypothalamic-pituitary-adrenal system. This could be an important survival mechanism to ensure that dysfunction of one neurotransmitter system will not endanger the appropriate secretion of hormones during exposure to adverse conditions. The measurement of several hormones to examine the mechanisms underlying the stress response and the effects of drugs and lesions on these responses can provide insight into the nature and location of brain circuits and neurotransmitter receptors involved in anxiety and stress.
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PMID:Neuroendocrine pharmacology of stress. 1260 Jul 14


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