UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
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The presence of three regulatory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-1, was studied by radioimmunoassay in the tumor tissue of an ACTH-secreting bronchial carcinoid. A 36-year-old female was admitted to hospital because of moon face, central obesity and hypertension. High levels of plasma ACTH and cortisol and urinary 17-OHCS and 17-KS were found. One mg dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotropin-releasing hormone (100 micrograms, iv) stimulated plasma ACTH levels (0 min; 34.8 pmol/l; 30 min; 41.1 pmol/l). The computerized tomography showed the presence of a tumor in the right lung. This lung tumor was removed surgically and has been shown by microscopical examination to be a bronchial carcinoid with ACTH-positive cells. The tumor tissue concentrations of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 were 3.34 pmol/g wet weight, 8.07 pmol/g wet weight and 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides were not elevated. Reverse phase high performance liquid chromatography showed that immunoreactive peptides in the tumor tissue were mainly eluted in the position of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in its tumor tissue and suggested that these peptides may act locally, in a paracrine or autocrine manner, in the tumor.
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PMID:An ACTH-secreting bronchial carcinoid: presence of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in the tumor tissue. 838 6

The wide distribution of corticotropin-releasing factor (CRF) and substance P (SP)-immunoreactive cell bodies, nerve terminals and corresponding receptors in pressor nuclei controlling emotion and stress implies that CRF and SP may play important roles in pressor responses of these nuclei; hence CRF or SP was microinjected into these nuclei respectively in Wistar male rats anesthetized with urethane to test this possibility. Microinjection of CRF into nucleus amygdaloideus centralis, nucleus paraventricularis, nucleus ventromedialis, lateral hypothalamus-perifornical region, periaqueductal gray matter, nucleus parabrachialis, locus coeruleus or rostral ventrolateral medulla respectively could evoke pressor responses (but CRF injection into nucleus dorsomedialis could not elicit significant pressor responses). Injection of substance P into all the above nuclei could also elicit hypertensive responses of different magnitudes, whereas normal saline injection into these nuclei had no effect. These results indicate that both CRF and SP in the above mentioned nuclei may play important roles in hypertension induced by prolonged emotional stress.
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PMID:Role of corticotropin-releasing factor and substance P in pressor responses of nuclei controlling emotion and stress. 962 22

Corticotropin-releasing factor is a 41-amino-acid neuropeptide synthesized in the paraventricular nucleus of the hypothalamus and released in response to stress. Its major role is the regulation of the hypothalamus-pituitary-adrenal axis by stimulation of ACTH release from the anterior pituitary gland. In addition, corticotropin-releasing factor modulates behavioral, vascular, and immune responses to stress. Corticotropin-releasing factor was first detected in the extracts of human placentas obtained at full term from spontaneous deliveries. Placental corticotropin-releasing factor content and messenger RNA expression progressively increase during normal pregnancy, and corticotropin-releasing factor levels in maternal plasma have a similar time course. The addition of corticotropin-releasing factor to primary trophoblast cell cultures stimulates ACTH secretion in a dose-dependent manner, and its action is mediated by cyclic adenosine monophosphate as second messenger. In addition, corticotropin-releasing factor is a potent local regulator of myometrial contractility and of membrane prostaglandin release. The effects of corticotropin-releasing factor in these various tissues are mediated by specific receptors. Placental corticotropin-releasing factor is also secreted into the fetal circulation and the stimulation of fetal pituitary ACTH and fetal adrenal gland dehydroepiandrosterone sulfate release in vitro has been shown. Recently, urocortin, a new peptide related to corticotropin-releasing factor, has been found in human placenta. Corticotropin-releasing factor and urocortin share some of their biologic effects, acting on the same receptors. A large-molecular-weight corticotropin-releasing factor-binding protein modulates the activity of both these peptides. Plasma corticotropin-releasing factor levels are low in nonpregnant women and become higher during the second trimester of pregnancy, rising steadily until about 35 weeks, and then increasing more rapidly until term. Vaginal delivery is a condition associated with the highest values of maternal corticotropin-releasing factor levels. Corticotropin-releasing factor is also measurable in fetal plasma (20-fold lower than in maternal circulation) and in amniotic fluid. Increased maternal plasma corticotropin-releasing factor levels characterize some gestational diseases. Women with chronic hypertension and preeclampsia have high corticotropin-releasing factor levels, and intrauterine growth retardation is associated with an activation of the hypothalamus-pituitary-adrenal axis, reflected by increased fetal plasma concentrations of ACTH, cortisol, and corticotropin-releasing factor. The role of corticotropin-releasing factor in preterm labor is uncertain, but midgestational plasma corticotropin-releasing factor levels may be higher in women delivering preterm. In these various pathologic states, maternal plasma corticotropin-releasing factor-binding protein levels undergo opposite changes, decreasing to very low levels. The endocrine-paracrine corticotropin-releasing factor/corticotropin-releasing factor-binding protein pathways may play a major role in the mechanism of human parturition.
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PMID:Putative role of placental corticotropin-releasing factor in the mechanisms of human parturition. 1037 66

Prolonged emotional stress is an important factor in the development of neurogenic hypertension, but its mechanism is still unclear. The purpose of the present study is to analyze the possible neural basis of hypertension induced by prolonged emotional stress. In the brain many nuclei are involved in emotional reaction, stress or defense response; among them the nucleus amygdaloideus centralis (AC) is the most important one which widely connects with other nuclei controlling emotion and stress, such as nucleus ventromedialis (NVM), nucleus dorsomedialis (NDM), nucleus paraventricularis (NPV) etc. These nuclei contain corticotropin releasing factor (CRF)- and substance P (SP)-immunoreactive cell bodies, nerve terminals and corresponding receptors. Our previous and present studies showed that microinjection of CRF or SP into these nuclei induced pressor responses. These data imply that excitation of the AC can activate many nuclei controlling emotion and stress via CRF and SP, and excessive activities of these nuclei may be the neural basis of hypertension induced by prolonged emotional stress. The present study revealed that (1) the AC pressor response to glutamate (Glu) could be reduced by preinjection of CRF antagonist (alpha-Helical CRF[9-41] or SP antagonist ([D-Pro(2), D-Phe(7), D-Trp(9)]-substance P) into bilateral NVM, (2) the NVM pressor response to Glu were decreased by pretreatment of the NDM with CRF- or SP-antagonist, (3) the AC-, NVM- or NDM-pressor responses were all attenuated by preinjection of CRF- or SP-antagonist into bilateral NPV or rostral ventrolateral medulla (RVL). The results indicate that excitation of the AC can indirectly activate the NPV and RVL to evoke pressor response via the NVM-NDM, CRF and SP are transmitters in each connection of this pathway; this is one component of the mechanism underlying the AC pressor response. Taken together with the findings of our previous studies, it provides neurophysiological basis for the above-mentioned implications.
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PMID:Corticotropin releasing factor and substance P mediate the nucleus amygdaloideus centralis-nucleus ventromedialis-nucleus dorsomedialis pressor system. 1052 35

Recent research has greatly expanded the domain of insulin action. The classical action of insulin is the control of glucose metabolism through the dual feedback loop linking plasma insulin with plasma glucose concentrations. This canon has been revised to incorporate the impact of insulin resistance or insulin deficiency, both of which alter glucose homeostasis through maladaptive responses (namely, chronic hyperinsulinaemia and glucose toxicity). A large body of knowledge is available on the physiology, cellular biology and molecular genetics of insulin action on glucose production and uptake. More recently, a number of newer actions of insulin have been delineated from in vitro and in vivo studies. In sensitive individuals, insulin inhibits lipolysis and platelet aggregation. In the presence of insulin resistance, dyslipidaemia, hyper-aggregation and anti-fibrinolysis may create a pro-thrombotic milieu. Preliminary evidence indicates that hyperinsulinaemia per se may be pro-oxidant both in vitro and in vivo. Insulin plays a role in mediating diet-induced thermogenesis, and insulin resistance may therefore be implicated in the defective thermogenesis of diabetes. In the kidney, insulin spares sodium and uric acid from excretion; in chronic hyperinsulinaemic states, these effects may contribute to high blood pressure and hyperuricaemia. Insulin hyperpolarises the plasma membranes of both excitable and non-excitable tissues, with consequences ranging from baroreceptor desensitisation to cardiac refractoriness (prolongation of QT interval). Under some circumstances insulin is vasodilatory-the mechanism involving both the sodium-potassium pump and intracellular calcium transients. Finally, by crossing the blood-brain barrier insulin exerts a host a central effects (sympatho-excitation, vagal withdrawal, stimulation of corticotropin releasing factor), collectively resembling a stress reaction. Description and understanding of these new roles, their interactions, the interplay between insulin resistance and hyperinsulinaemia, and their implications for cardiovascular disease have only begun.
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PMID:Insulin: new roles for an ancient hormone. 1058 26

Cocaine abuse and HIV disease each have potentially adverse effects upon the heart and cardiovascular system which may be exacerbated when these risk factors are combined. The development of a safe and effective agent to treat both cocaine addiction and its cardiovascular sequelae, that is well-tolerated by HIV patients, would thus be of considerable clinical utility. In this article we discuss the rationale for the investigation of angiotensin converting enzyme (ACE) inhibitors, commonly used to treat hypertension, for treatment in cocaine-abusing populations, based on their potential to reduce cocaine use by modulating levels of dopamine and corticotropin releasing factor in the brain, and on their ability to reverse cardiovascular and platelet abnormalities. We present preliminary findings from echocardiographic and platelet activation studies in 16 HIV-positive, cocaine abusing patients, as well as tolerability and efficacy studies of the ACE-inhibitor, fosinopril, for the treatment of cocaine abuse in both HIV-positive (n=6) and HIV-negative (n=5) methadone-maintained cocaine abusers. Findings suggest that HIV-positive cocaine-abusing patients possess abnormalities of diastolic heart function and platelet activation that are potentially reversible with ACE-inhibitor therapy. Findings also suggest that fosinopril is well-tolerated regardless of HIV serostatus, does not appear to cause hypotension, and may possess effectiveness for reducing cocaine use. We conclude that ACE-inhibitor therapy may offer a new pharmacologic approach to the treatment of cocaine abuse and its complications, and that controlled research of this class of agents may be promising.
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PMID:Cocaine, HIV, and their cardiovascular effects: is there a role for ACE-inhibitor therapy? 1106 82

Endogenous opioids target noradrenergic locus ceruleus (LC) neurons and potently inhibit LC activity. Nonetheless, it has been difficult to demonstrate functional regulation of the LC-noradrenergic system by endogenous opioids because of the lack of effect of opiate antagonists. The present findings provide evidence that endogenous opioids regulate LC neuronal activity during the termination of a stressor. LC neuronal discharge was recorded from halothane-anesthetized rats before, during, and after hypotensive stress elicited by intravenous nitroprusside infusion. In naive rats, mean arterial blood pressure was temporally correlated with LC activity such that hypotension was associated with increased LC discharge and a return to the normotensive state was associated with a decrease in LC discharge below pre-stress values. After microinfusion of an antagonist of the stress neuropeptide corticotropin-releasing factor (CRF) into the LC, the increase in LC discharge associated with hypotension was prevented, whereas LC inhibition associated with termination of the challenge occurred at an earlier time and was of a greater magnitude. In contrast, microinfusion of naloxone into the LC completely abolished LC inhibition associated with termination of the stressor. Naloxone microinfusion did not prevent LC inhibition associated with hypertension produced by intravenous vasopressin administration, suggesting that endogenous opioids may be selectively engaged during the termination of hypotensive stress. These results provide evidence for a functional release of endogenous opioids within the LC. This action of endogenous opioids may serve to counterbalance excitatory effects of CRF on the LC-norepinephrine system, thereby limiting its activation by stress.
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PMID:Evidence for functional release of endogenous opioids in the locus ceruleus during stress termination. 1140 37

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. Alterations in the following substances are discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, and corticotropin-releasing factor. Functional changes in these substances occur throughout the hypothalamus but are particularly prominent rostrally; most lead to an increase in sympathetic nervous activity which is responsible for the rise in arterial pressure. A few appear to be depressor compensatory changes. The majority of the hypothalamic changes begin as the pressure rises and are particularly prominent in the young rat; subsequently they tend to fluctuate and overall to diminish with age. It is proposed that, with the possible exception of the Dahl salt-sensitive rat, the hypothalamic changes associated with hypertension are caused by renal and intrathoracic cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a result of renal ischemia and trauma as in the reduced renal mass rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it is submitted, is due to the associated documented impaired ability to excrete sodium. It is proposed, therefore, that the hypothalamic changes in hypertension are a link in an integrated compensatory natriuretic response to the kidney's impaired ability to excrete sodium.
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PMID:The hypothalamus and hypertension. 1158 98

There is an emotional pressor circuit composed of nuclei controlling emotion and stress, which may be the neurophysiological basis for prolonged emotional stress inducing hypertension. The central amygdaloid nucleus (AC) is the most important in this circuit, which widely connects with the other nuclei via its CRF (corticotropin releasing factor)-ergic and SP (substance P)-ergic projection fibers. There is another pressor system composed of the lateral septum (SL), habenula (HB), locus coeruleus (LC), and rostral ventrolateral medulla (RVL); muscarinic receptors are involved in each connection of this system. In view of the facts that the SL also plays an important role in integration of emotion and autonomic reaction, and the AC projects to the SL, it is likely that the SL-acetylcholine (ACh) pressor system is involved in the AC-emotional circuit. The present study demonstrates that injection of receptor blocker into each nucleus in the SL-ACh pressor pathway can reverse the AC pressor response, proving that the SL-HB (and HB-posterior hypothalamus)-LC-RVL pressor system is a component of the AC-emotional pressor circuit.
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PMID:Involvement of rat lateral septum-acetylcholine pressor system in central amygdaloid nucleus-emotional pressor circuit. 1191 90

Behavioral stress is likely to contribute to the development of hypertension in susceptible individuals. We reported that hemodynamic response patterns to acute startle vary and that those patterns predict the predisposition of rats to sustained stress-induced elevations in arterial pressure. Since considerable evidence suggests that central catecholamines and corticotropin releasing factor (CRF) contribute to the regulation of arterial pressure and the development of hypertension, we investigated the role of central alpha-adrenergic receptors and CRF in mediating different hemodynamic response patterns to acute cold water stress in conscious rats. Rats were instrumented for arterial pressure, heart rate and cardiac output determination and for intracerebroventricular (icv) administration of selective antagonists. After acclimation to a water tight cage, ice water (1 cm deep) was rapidly added then drained 1 min later. Although the early startle response to cold water stress elicited a pressor response in all rats, the hemodynamic response pattern varied between rats. Vascular responders (n=19) had an initial considerable increase in systemic vascular resistance and a decrease in cardiac output. In contrast, mixed responders (n=11) had a smaller increase in vascular resistance and an increase in cardiac output. Pretreatment with phentolamine (30 microgram/5 microliter, icv, n=8), prazosin (10 microgram/5 microliter, icv, n=12) or alpha-helical CRF(9-41) (10 microgram/5 microliter, icv, n=9) prevented the decrease in cardiac output elicited by acute cold water stress in vascular responders without affecting mixed responders. Yohimbine (3 microgram/5 microliter, icv, n=8) pretreatment did not alter hemodynamic responses. Therefore, we conclude that central alpha(1)-adrenoceptors and CRF mediate the specific hemodynamic response patterns to acute startle and may be responsible for the predisposition to develop hypertension in vascular responders.
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PMID:Central alpha-adrenergic receptors and corticotropin releasing factor mediate hemodynamic responses to acute cold stress. 1264 70

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