Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a laboratory exercise that demonstrates arterial baroreflex control of heart rate (HR) in the conscious unrestrained rat, incorporating graduate level physiological topics as well as a hands-on exposure to conscious animal research. This demonstration utilizes rats chronically instrumented to measure cardiac output (CO), HR, and arterial blood pressure in response to agents that raise or lower blood pressure. The HR response to progressive increases or decreases in blood pressure is recorded, and a baroreflex curve is generated by plotting mean arterial blood pressure (MABP) vs. HR. Observation of altered CO allows for discussion of the relationship between MAP, CO, HR, stroke volume, and total peripheral resistance. Administration of arginine vasopressin demonstrates the ability of this hormone to alter the sensitivity of the baroreflex. Throughout the demonstration, students answer questions from a handout about general cardiovascular physiology, specific pathways of agonists, and the baroreflex system, encouraging group and individual critical analysis of the results. Interpretation of the data reemphasizes lecture material and allows students to observe the baroreflex response in a physiological setting.
 ...
PMID:Laboratory demonstration of baroreflex control of heart rate in conscious rats. 1244 3

The septic shock is characterized by decrease in median arterial pressure; many researchers have been related a deficiency in vasopressin release during the septic shock. Lipopolysaccharide administration is used to induce septic shock model in animals. We investigated the heme-oxygenase (HO) inhibition during the endotoxemic shock-like conditions. The LPS administration induced a significant decrease in MAP (-15.4 +/- 1.2 mmHg at second hour, -25.8 +/- 8.7 mmHg at fourth hour, and -22.3 +/- 8.6 mmHg at sixth hour) with a concomitant increase in heart rate (486.3 +/- 55.0, 531.8 +/- 53.8, and 510.0 +/- 55.3 bpm, respectively), a significant decrease in diuresis (from 1.1 +/- 0.7 to 0.4 +/- 0.3/100g body weight at fourth hour), and a transitory decrease in body temperature (from 37.0 +/- 0.5 to 35.4 +/- 0.8 degrees C at second hour). An increase in plasma arginine vasopressin (AVP) concentration (from 3.2 +/- 0.9 to 19.0 +/- 5.7 pg/mL at the first hour) occurred in these animals and was present for 2 h after LPS administration, returning close to basal levels thereafter and remaining unchanged until the end of the experiment. When LPS was combined with the i.c.v. administration of HO inhibitor, we observed a sustained increase in plasma AVP concentration, attenuation in the drop of MAP, and increase in antidiuresis induced by LPS treatment. These data suggest that central HO pathway may activate a control mechanism that attenuates AVP secretion during endotoxemia and may consequently regulate the MAP and diuretic output.
 ...
PMID:Role of heme-oxygenase pathway on vasopressin deficiency during endotoxemic shock-like conditions. 1704 17

Although arginine vasopressin and terlipressin have been identified as useful nonadrenergic agents to increase systemic blood pressure in catchecholamine-resistant septic shock, the impairments in cardiac index (CI) and global oxygen transport may limit their clinical applicability. The present study was designed as a prospective controlled laboratory experiment to investigate the effects of dobutamine as an adjunct to terlipressin infusion on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. Nine adult ewes were instrumented for chronic study using an established protocol. After a baseline measurement in the healthy state had been performed, 1 mg terlipressin was given as bolus infusion. Thirty minutes later, dobutamine was continuously infused at incremental doses (2 and 5 microg x kg(1) x min(1), each for 1 h). After 24 h of recovery, a hypotensive-hyperdynamic circulation was induced and maintained by a continuous infusion of Salmonella typhosa endotoxin (10 ng x kg(1) x min(1)). After 16 h of endotoxemia, the six surviving sheep received terlipressin and dobutamine according to the same protocol that was used in healthy sheep. Compared with baseline, terlipressin infusion was associated with a significant increase in MAP that, however, occurred at the expense of a compromised CI, oxygen delivery index (DO(2)I), and mixed venous oxygen saturation (SvO(2), each P < 0.05). Dobutamine infusion was followed by a dose-dependent increase in CI, DO(2)I, and SvO(2) in both health and endotoxemia (each P < 0.05). Although the higher dosage of dobutamine exerted favorable effects, such as a decrease in pulmonary vascular resistance index (P < 0.05), the associated onset of tachycardia (P < 0.05) and arterial hypotension (P < 0.05) may limit its therapeutic use under septic conditions. This study provides evidence that dobutamine in a dosage of 2 microg x kg(1) x min(1) is useful to reverse the terlipressin-linked depressions in CI, DO(2)I and SvO(2) in ovine endotoxemia without obvious side effects.
 ...
PMID:Employing dobutamine as a useful agent to reverse the terlipressin-linked impairments in cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. 1766 52

Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are unknown. Arginine vasopressin is considered to play an important role in severe hemorrhage. In this prospective study, 87 multiple trauma patients (Injury Severity Score >15) and 50 healthy volunteers were enrolled. On admission to the emergency department (ED), demographic, clinical, and laboratory data were documented, and blood was sampled for determination of AVP (radioimmunosassay) and copeptin, a stable fragment of the AVP precursor (immunoluminometric assay). In patients requiring intensive care unit (ICU) therapy, blood and data sampling were repeated at 4, 6, and 24 h after ED admission. Linear logistic and mixed-effects regression analyses were used for statistical analysis. On ED admission, AVP plasma concentrations (43.2 +/- 84.9 pM) were significantly increased when compared with controls (0.92 +/- 0.44 pM, P < 0.001). Plethysmographic oxygen saturation was the only parameter independently associated with AVP (regression coefficient, -0.126; 95% confidence interval, -0.237 to -0.014; P = 0.03). No correlation was observed between AVP and survival (P = 0.62), hemodynamic variables (systolic arterial pressure, P = 0.24; MAP, P = 0.59; diastolic arterial pressure, P = 0.74; central venous pressure, P = 0.36), or brain trauma (P = 0.46). In ICU patients, AVP decreased during the first 24 h (P < 0.001) and was independently associated with heart rate (P = 0.02) and blood glucose (P = 0.009). Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001). In conclusion, AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission.
 ...
PMID:Endogenous vasopressin and copeptin response in multiple trauma patients. 1809 79

Neuroactive steroids synthesized from the brain or peripheral sources are called neurosteroids. Beside their common nuclear effects, they are considered to be potent neuromodulators, acting rapidly mainly in a non-genomic manner, either through allosteric regulation of ionic channels, or through membrane-bound steroid receptors. In contrast to the situation in the adult, the neurotransmitter GABA is excitatory during development and plays a trophic role, in particular inducing calcium signals necessary for the regulation of excitability and neuronal maturation. We demonstrated that the primary metabolite of progesterone (Proges), allopregnanolone (Allo), evoked a robust Ca(2+) influx in foetal hypothalamic neurons and in postnatal supraoptic nucleus (SON) neurons. In the latter, this led to oxytocin and arginine vasopressin release. Interestingly, these responses were GABA(A) and oxytocin-receptor-dependent. Allo is a well-known positive allosteric modulator of GABA(A) receptors. It is noteworthy that two other steroids, Proges and 17-beta-estradiol, displayed the same effect on Ca(2+) and oxytocin release but to a lesser extent. Importantly, no effect was observed in adult neurons from the SON, or in neurohypophysial axon terminals, regardless of the stage. The molecular mechanisms of the neurosteroid actions are multifaceted and depend on the type of cells, and are thus extremely interesting and challenging. In the peripheral nervous system, Allo and Proges surprisingly inhibited the GABA-induced Ca(2+) increases in embryonic dorsal root ganglion neurons. We propose that this rapid, reversible and dose-dependent phenomenon (at very low concentrations) was mediated by membrane Proges receptors, since transcripts for a newly discovered receptor protein, 25-Dx, were detected in our model. Recently, novel families of membrane steroid receptors, activating intracellular-signalling pathways such as MAP kinases, have been identified and described. This opens new perspectives to understand the intracellular machinery involved in the interaction between neuropeptides and neurosteroids, two major regulators of hypothalamo-neurohypophysial system development.
 ...
PMID:Neurosteroids are excitatory in supraoptic neurons but inhibitory in the peripheral nervous system: it is all about oxytocin and progesterone receptors. 1865 82

The 5-HT(1A) receptor agonist, 8- OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine whether improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA), and blood gases were compared in hemorrhaged rats following administration of 5-HT(1A) receptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (approximately 2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP, and protection against metabolic acidosis produced by 8-OH-DPAT but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT.
 ...
PMID:The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat. 1924 81

Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-knockout mice with arginine vasopressin (AVP) for 2 weeks, controlling their water intake, or giving them an osmotic diuretic (sucrose) in order to determine whether central or nephrogenic mechanisms were involved. Under basal conditions, AT(1a)-knockout mice were hypotensive, had lower plasma AVP, and excreted more urine with a markedly reduced osmolality compared with wild-type mice. However, basal glomerular filtration rates were similar in both strains of mice. We isolated total lysate and membrane proteins from the inner medulla of wild-type and mutant mouse kidneys, and found that the amounts of aquaporin 2 (AQP2), adenylyl cyclases III and V/VI, and phosphorylated MAP kinases ERK 1/2 proteins were all reduced in the inner medulla of the knockout mice. Infusion of AVP raised plasma levels and blood pressure proportionally in both strains, but polyuria persisted and urine osmolality remained significantly lower in the knockout mice. Although AVP increased urine osmolality slightly in water-deprived knockout mice, this was well below the basal osmolality of wild-type mice. The diuretic response to the hyperosmotic sucrose was also impaired in the knockout mice. Neither AVP nor water rationing restored the levels of the inner medullary signaling proteins and membrane AQP2 proteins in the knockout mice. We suggest that AT(1a) receptor deletion causes polyuria and urine concentration defects by decreasing basal AVP release and impairing AVP-induced receptor signaling in the inner medulla.
 ...
PMID:AT1a receptor knockout in mice impairs urine concentration by reducing basal vasopressin levels and its receptor signaling proteins in the inner medulla. 1956 56


<< Previous 1 2 3