UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NG-Methyl-L-arginine (NMA), an inhibitor of nitric oxide synthesis by vascular endothelium, depresses cardiac function and causes systemic vasoconstriction in vivo. The mechanism of cardiac depression is unclear. Since cGMP inhibits one isoform of myocardial phosphodiesterase (PDE), we hypothesized that a decrease in cGMP might increase PDE activity and lower myocardial cAMP levels, resulting in decreased contractility. Experiments were conducted in isolated, paced, Langendorff-perfused (constant flow) rat hearts under control or isoproterenol-stimulated conditions. In non-stimulated hearts, a 15 min infusion of 30 microM NMA had no effect on cAMP content or on left ventricular dP/dt; however, myocardial cGMP content was decreased. Infusion of 0.01 microM isoproterenol caused dP/dt to increase and caused coronary resistance to fall; myocardial cAMP levels increased while cGMP remained unchanged by isoproterenol. In this stimulated condition, infusion of 30 microM NMA decreased dP/dt and myocardial cGMP and cAMP concentrations. NMA caused coronary resistance to increase to similar maximal values in isoproterenol-stimulated and non-stimulated hearts. Although coronary flow was kept constant during NMA administration, NMA depressed cardiac contractility in isoproterenol-stimulated hearts, but not in non-stimulated hearts, and the depressed contractility in isoproterenol-treated hearts was associated with a decrease in myocardial content of cGMP and cAMP. Therefore, these results are consistent with the hypothesis that NMA may decrease myocardial contractility by decreasing cGMP which leads to increased PDE activity and decreased cAMP.
...
PMID:NG-methyl-L-arginine decreases contractility, cGMP and cAMP in isoproterenol-stimulated rat hearts in vitro. 133 73

The prostaglandin system is impaired in cholestasis; bile salts, which are a specific biochemical feature of this condition, have been shown to affect functional properties of cells and tissues, and, in some cases, their action is mediated through an alteration of prostaglandin pathway. Endothelium is a privileged site for the production and the action of arachidonate metabolites-prostacyclin in particular. To determine the effects of bile salts on the properties of vascular endothelium, cultured human endothelial cells were studied. Cholic acid sodium salt was seen to induce a direct injury on endothelial cells, as was demonstrated by a massive dismission of the intracellular radiolabel chromium 51. In the absence of detectable toxic effect, sodium taurocholate caused a significant depression of prostacyclin constitutive production from human endothelial cells. The action of sodium taurocholate was related to its concentration and to the time of exposure, and the alteration of prostacyclin production was found to be reversible. Conversely, the generation of thromboxane A2 was not influenced by this bile salt, which may suggest a specific action of sodium taurocholate on arachidonic acid metabolism. These findings indicate that bile salts may directly alter some functional properties of cultured human endothelial cells and may provide a basis for explaining some generalized manifestations that are observed in pathologic conditions characterized by cholemia.
...
PMID:Sodium taurocholate affects prostacyclin constitutive production by cultured human vascular endothelial cells. 211 71

Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy.
...
PMID:Cerebral autoregulation. 220 48

Encephalitozoonosis was identified for the first time in arctic lemmings (Dicrostonyx stevensoni and crosses of D. stevensoni and Dicrostonyx rubricatus). The most common clinical findings were circling, torticollis, posterior paralysis, depression, blindness and death related to parasitic granulomas in many tissues. Granulomas were most frequent in the central nervous system, but were seen in many other tissues throughout the body. Granulomas were characterized by collections of macrophages and varying numbers of lymphocytes and neutrophils with or without necrosis of parenchymal tissue. Most granulomas contained protozoon cysts with ultrastructural characteristics of Encephalitozoon cuniculi. Protozoon cysts were seen in vascular endothelium in many tissues accompanied by minimal or no inflammatory reaction.
...
PMID:Encephalitozoonosis in arctic lemmings. 247 90

The pulmonary vascular endothelium, a metabolically active tissue, serves as an important site of injury in many types of clinical and experimental lung disease. Removal of 5-HT from the circulation constitutes one of the endothelial metabolic functions that is depressed early in the course of lung injury. Experimental evidence confirms that measuring 5-HT uptake detects alterations in endothelial cell function that precede the abnormalities detected by more conventional diagnostic tests such as radiographs, pulmonary function tests, and arterial blood gases. In addition, depression of 5-HT uptake can lead to increased concentrations of 5-HT in the pulmonary vasculature, which may contribute to the pathogenesis of lung injury. The development of an ideal method for measuring 5-HT uptake accurately in the lungs of critically ill patients has just begun. As yet, numerous variables reviewed in this article confound clinical measurements of 5-HT uptake. However, if investigators can continue to refine and develop the techniques for measuring 5-HT uptake in human patients, clinicians can look forward to the addition of a sensitive tool to their diagnostic armamentarium. Hopefully, the ability to detect diffuse lung injury earlier in its course will enable future clinicians to institute therapy that will prevent the pathologic progression to morbidity and death seen all too frequently in current medical practice.
...
PMID:Lung serotonin metabolism. 265 Sep 64

The vascular activity of arginine vasopressin (AVP) and selective AVP receptor antagonists was investigated in isolated arterial ring segments from human superior mesenteric arteries. AVP elicited a potent and concentration-dependent contraction in human mesenteric arterial rings with an EC50 value of 2.01 X 10(-9) M. The presence or absence of the vascular endothelium did not affect significantly AVP-induced contraction. AVP induced slight, although significant, tachyphylaxis in human mesenteric arteries. The selective vascular (V1) receptor antagonist [d(CH2)5 1Tyr(Me)2]AVP (SK&F 100273) shifted the concentration-response curves for AVP-induced vascular contraction to the right in a parallel manner (KB = 2.23 X 10(-9) M). A mixed V1/V2 receptor antagonist, [d(CH2)5 1D-Tyr(Et)2Val4desGly9]AVP (SK&F 101926), was also a potent antagonist of AVP-mediated vascular contraction; however, inhibition was marked by a nonparallel shift of the concentration-response curves with depression of maximum contraction. Furthermore, a relatively renal (V2) selective receptor antagonist [d(CH2)5 1D-Ile2Val4]AVP (SK&F 101485) was approximately 100-fold less potent at inhibiting AVP-induced vascular contraction (KB = 1.37 X 10(-7) M). These studies illustrate for the first time the in vitro effects of selective vasopressin receptor antagonists in isolated human blood vessels. Studies of other blood vessels and the design of therapeutically useful antagonists should proceed with the hypothesis that the vasopressin receptors mediating vascular contraction in human mesenteric arteries are of the V1 subtype.
...
PMID:Human vascular vasopressin receptors: analysis with selective vasopressin receptor antagonists. 294 8

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Acetylcholine-induced pulmonary vasodilation in lung vascular injury. 300 69

To determine the pattern of cellular expression of donor MHC class I and class II antigens during the course of rat cardiac allograft rejection, ACI cardiac allografts transplanted to BN recipients were examined from day 2 to day 6 using immunohistologic and immunoelectron microscopic methods. We used both monomorphic and donor-specific mouse anti-rat MHC class I and class II mAbs in this study. In normal ACI hearts, MHC class I reactivity was confined to the vascular endothelium and to interstitial cells. Ongoing rejection was characterized by an increased donor MHC class I staining intensity of microvascular endothelium and induction of donor class I surface reactivity on cardiac myofibers. Donor MHC class II reactivity was exclusively confined to interstitial dendritic cells (IDC) in both normal ACI hearts and in rejecting allografts, although rejection was associated with marked fluctuations in class II IDC frequency. An early numerical depression in class II IDC present in both allografts and syngeneic heart grafts was attributed to a direct effect of the transplantation procedure. By days 3-4, allografts showed an absolute overall increase in donor class II IDC frequency, which was associated with the presence of multiple localized high-density IDC-lymphocyte aggregates. The lymphocytes present in the focal areas were predominantly of the class II-reactive Th cell subpopulation. These aggregates may thus represent the in vivo homologue of dendritic cell-lymphocyte clustering, which has been shown to be required for primary class II allosensitization in the rat and mouse in vitro. During the late phase of rejection, there was a marked numerical fall in donor class II IDC, which correlated with extensive overall graft destruction. This study has shown that acute rat cardiac allograft rejection can occur in the absence of donor MHC class II expression by allograft vascular endothelium and cardiac myofibers. The IDC, which are believed to represent the principal class II alloantigen presenting cells in the rat heart, remain the sole class II-expressing cellular constituents of the graft throughout the course of rejection.
...
PMID:Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection. 353 83

A previous study of endotoxemia in dogs demonstrated that exogenous prostacyclin (PGI2), normally a product of vascular endothelium, restored the cardiac index to normal and improved survival. To account for these results, a study was undertaken to test whether PGI2 would alter isolated rat or dog cardiac mitochondrial function following incubation with plasma from endotoxemic animals. A group of five animals served as anesthetized controls. A second group of seven mongrel dogs was given 1.75 mg Escherichia coli endotoxin/kg and was observed for 5 hours without treatment. Anesthesia did not alter cardiopulmonary function; however, 30 minutes after endotoxin administration, the cardiac index decreased from 148 +/- 25 (mean +/- SD) to 111 +/- 12 ml/kg . min (P less than 0.05) and further decreased to 89 +/- 20 ml/kg . min after 4 hours. Dog plasma obtained 2 to 5 hours after endotoxin infusion, incubated with rat or dog myocardial mitochondria, decreased succinate dehydrogenase (SDH) activity (P less than 0.05) and depressed mitochondrial respiration in the presence of the substrate succinate and adenosine diphosphate (ADP) from 180 to 87 Natoms oxygen/mg protein . min (P less than 0.05). There was no change in oxygen consumption when substrate alone was present, nor did plasma alter the amount of ADP phosphorylation as a function of oxygen consumption. A third group of seven animals, 30 minutes after administration of 1.75 mg endotoxin/kg, was treated with 100 ng/kg . min PGI2 for 3 hours. PGI2 infusion in this group prevented the decrease in cardiac index. Plasma obtained during and after PGI2 infusion did not decrease mitochondrial SDH activity, which remained higher than that in controls (P less than 0.001); mitochondrial respiration was also not altered. A correlation was observed between cardiac index and SDH activity (r = 0.58, P less than 0.001) and between cardiac index and mitochondrial respiration (r = 0.61, P less than 0.001). In PGI2-treated dogs cardiac mitochondria were functionally and structurally normal in contrast to the depression and disruption produced by endotoxemia, as observed by enzymatic assay as well as electron microscopy. These results suggest that endotoxemia depresses cardiac mitochondrial respiration, an event related to the decrease in cardiac index. In contrast, cardiac function and mitochondrial respiration are maintained with PGI2 treatment.
...
PMID:Myocardial protection with prostacyclin after lethal endotoxemia. 704 19

Splanchnic arterial occlusion shock results in pulmonary endothelial damage and depression of porcine intralobar pulmonary artery and vein contractility. This study evaluates the functional integrity of the adrenergic nerves innervating intralobar pulmonary arteries and veins and the changes in neurotransmission following 1) superior mesenteric artery occlusion (SMAO) shock in swine; 2) sequential inhibition of prostacyclin, thromboxane, and prostaglandin synthesis; and 3) mechanical stripping of the endothelium. Rings of porcine intralobar pulmonary arteries and veins were obtained from sham and SMAO shocked swine. They were suspended in muscle baths and stimulated transmurally at 1-32 Hz, 2 msec duration, 2 msec delay at 7.5-10V. Some experiments were performed on rings of intralobular pulmonary arteries and veins in which the endothelium was stripped with a razor blade. Appropriate inverted-reverted controls were used to account for any deleterious effects of the preparatory techniques involved in stripping. Intralobar pulmonary arteries and veins from sham swine contracted in response to 1 Hz, with maximum responses at 32 Hz. The responses to nerve stimulation were enhanced by cocaine and inhibited by phentolamine, an alpha-receptor antagonist. Inhibition of endothelial prostacyclin synthesis, as well as endothelial stripping, diminished by 30-40% the responses to nerve stimulation. The responses to nerve stimulation were depressed in both intralobar pulmonary arteries and veins in SMAO shocked swine. The data demonstrate physiologic regulation of neural control in porcine pulmonary blood vessels. Furthermore, the data suggest that prostaglandin, the vascular endothelium, and shock, may modify this process.
...
PMID:Sympathetic neuroeffector transmission to pulmonary vascular smooth muscle in porcine superior mesenteric arterial occlusion (SMAO) shock. 731 16

1 2 3 4 5 Next >>