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)

The aim of this study was to assess the minimum time interval necessary to avoid the development of tolerance during nitroglycerin patch application. We studied 24 patients, aged 23 to 73 years, with ischemic or idiopathic dilated cardiomyopathy (LV EF less than 0.40) and stable clinical conditions during 30 days before the study. All patients had significant reduction of systemic and pulmonary arterial pressure after sublingual nitroglycerin. After the hemodynamic assessment of the response to the first dose of the nitroglycerin patch, the patients were randomized to 1 of 3 chronic treatment groups: continuous patch application (Group A), intermittent application with 4 hours intervals (Group B), intermittent application with 6 hours intervals (Group C). All patients were studied by right heart Swan-Ganz catheterization; the hemodynamic response to a 10 mg multilayer matrix nitroglycerin patch was assessed before and every hour, in the next 4 hours, after both the first application of the patch and after 1 month of therapy; after chronic intermittent therapy, hemodynamic parameters were also measured 24 hours after drug withdrawal. Hemodynamic parameters were significantly changed after the first nitroglycerin patch application: particularly, mean systemic arterial (MAP), right atrial (RAP) and pulmonary wedge pressures (PWP) declined from 96 +/- 10, 8.9 +/- 1.8 and 20.1 +/- 5 to 81 +/- 6, 4.7 +/- 1.5 and 12.2 +/- 3 mmHg (-15.6, -47.2 and -59.3%, respectively); systemic vascular resistance (SVR) and heart rate (HR) were reduced from 1645 +/- 121 to 1288 +/- 89 dyne.s.cm-5 and from 85 +/- 7 to 81 +/- 7 b/min; lastly, cardiac index (CI), stroke volume (SVI) and stroke work index (SWI) increased from 2.3 +/- 0.3, 28.2 +/- 5 and 28.7 +/- 9 to 2.7 +/- 0.3 l/min/m2, 33.3 +/- 5 ml/min/m2 and 31.5 +/- 8 g.m/m2 (+17.4, 18.1 and 9.7%). After 1 month of either continuous or intermittent patch application with 4 hours intervals, hemodynamic parameters returned to control values with no significant change after patch application. In contrast, after intermittent patch application with 6 hours intervals, a persistent hemodynamic response to nitroglycerin patches was still present.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The acute, chronic continuous after treatment and chronic intermittent with a variable therapeutic window (4 and 6 hours) hemodynamic effects induced with transdermal nitroglycerin in patients with congestive heart failure]. 176 29

Co-storage of enkephalins and catecholamines in coronary artery, mesenteric artery and vein, middle cerebral artery, vas deferens and adrenal medulla was studied in domestic pig (Sus scrofa). Responses to acute CNS ischemia were correlated with time to peak plasma levels of central venous and adrenal vein outflow samples in controls, during reserpine treatment and after drug withdrawal. Endogenous enkephalins are co-stored in chromaffin granules of adrenal epinephrine-type cells and large dense cored vesicles of noradrenergic terminals. After a lag period, reserpine at near 'therapeutic' doses caused an apparent induction of opioid peptide precursor synthesis accompanied by processing to enkephalins in adrenal medulla up to 8-fold by 30 days and in mesenteric vein up to 4.5-fold by 14 days. Upon 14 days recovery from reserpine, elevated adrenal enkephalins were maintained and depleted catecholamines were largely replenished. Acute CNS ischemia produced rises in MAP (approx. 80 mmHg), marked net depletions of noradrenergic enkephalin stores, and net increases in adrenal vein outflow and central venous levels of enkephalins and catecholamines. Noradrenergic terminals contributed significantly to circulating enkephalins as well as norepinephrine. Reserpine for 7 days nearly abolished all tested responses to acute CNS ischemia, but immediate net 200-400% elevations of endogenous enkephalin stores occurred in coronary artery and mesenteric artery and vein (apparent processing of reserpine-induced neuronal precursor stores). Thus, induction of new synthesis of precursor opioid peptides by reserpine, with or without parallel processing to enkephalins, occurs in noradrenergic terminals in many tissues. All effects of reserpine on endogenous enkephalins implicate a central mechanism to inhibit sympathoadrenal outflow to the periphery. At 14 days recovery from reserpine, when near normal cardiovascular responses to acute CNS ischemia were regained, there was increased net release of the elevated adrenal enkephalins, exaggerated peak plasma enkephalin concentrations, but only minimal depletions of enkephalins from noradrenergic terminals.
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PMID:Neuronal and adrenal enkephalins and catecholamines in response to acute CNS ischemia and reserpine in pig. 234 53

Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration were investigated. We confirmed that reverse tolerance in stereotyped behavior was constructed up to the 28th day after repeated intermittent pretreatment with increasing doses of MAP (2.5, 5, and 7.5 mg/kg x 3 and 10 mg/kg x 2, every other day). During acoustic stimulation, locomotor activity in the saline group was significantly increased, but the activity after the stimulation was completely suppressed. In contrast to the saline group, locomotor activity was not influenced by the acoustic stimulation in the MAP group, suggesting that behavioral hyporesponsiveness to acoustic stimulation was induced by MAP treatment. Two days after the last injection, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyphenylacetic acid (5-HIAA) in the cerebral cortex, midbrain + thalamus, hypothalamus and striatum were significantly decreased. These changes were maintained up to the 28th day after the drug withdrawal in the cerebral cortex and the midbrain + thalamus. From these results, the persistence of behavioral hyporesponsiveness to acoustic stimulation might be associated with long-lasting reduction of 5-HT synthesis.
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PMID:[Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration]. 237 84

Angiotensin I converting enzyme inhibition (ACEi) has been shown to lower urinary protein excretion in human renal disease. The mechanism of this antiproteinuric effect is hypothesized to be mediated by changes in renal hemodynamics. However, clinical studies suggest that the effect on renal hemodynamics is fully established immediately after the start of treatment, whereas others show the antiproteinuric effect to reach maximum only after several weeks. To clarify this issue we studied the course of renal hemodynamics, blood pressure and proteinuria during 28 days of ACEi (enalapril 10 mg oid) in nine patients with proteinuria due to non-diabetic renal disease. The effect of ACEi on blood pressure and renal hemodynamics was already maximal within few hours after start of treatment, and remained stable thereafter: MAP was lowered with 8.6 +/- 1.9%, 10.6 +/- 2.1%, 12.8 +/- 2.3% and 12.9 +/- 2.5%, while FF fell 23.0 +/- 2.0%, 17.0 +/- 2.6%, 16.8 +/- 2.8% and 15.9 +/- 4.0% on days 1, 7, 14 and 28 of ACEi, respectively. However, the antiproteinuric effect only gradually reached its maximum on day 28. Urinary protein excretion decreased with 10.9 +/- 6.1%, 32.7 +/- 6.2%, 46.3 +/- 2.5% and 54.0 +/- 2.5% on days 1, 7, 14 and 28 of ACEi, respectively. After drug withdrawal all parameters returned towards baseline. We conclude that a dissociation occurs in the course of the ACEi induced effects on hemodynamics and urinary protein excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dissociation between the course of the hemodynamic and antiproteinuric effects of angiotensin I converting enzyme inhibition. 823 Oct 31