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

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5-HT-2 antagonist ketanserin (KAS) has been successfully used to treat acute hypertension in coronary bypass surgery. The present study was performed to investigate the effect of KAS on ischaemic myocardium. In 11 anaesthetized (piritramide) dogs, systolic contraction (sdL) and end-diastolic length (edL) of myocardium supplied by the left descending coronary artery (LAD) and the left circumflex coronary artery (LCX) were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular dP/dtmax and end-diastolic pressure (LVedP), heart rate (HR), stroke volume, and LAD flow (QLAD). Regional ischaemia to decrease sdLLAD (-48%) was achieved by LAD stenosis (QLAD -47%). Concomitantly, edLLAD increased by 8%. However, the other variables did not change. Then KAS was given i.v. (0.15 + 0.15 + 0.30 + 0.6 mg/kg) at 15-min intervals. Following KAS, prestenotic sdLLAD recovered in a dose-dependent manner. LVedP and edLLAD decreased, sdLLCX increased, and the other variables were not affected. This functional recovery of ischaemic myocardium was attenuated by pretreatment with metoprolol (MET, 1 mg/kg) prior to LAD stenosis. The ischaemic area was not irreversibly damaged, however, as proven by the recovery of prestenotic sdLLAD values after release of the stenosis. The improved systolic shortening of ischaemic myocardium following KAS did not result from restored QLAD due to post-stenotic vasodilation or break up of platelet aggregates (QLAD did not increase) or from reduced afterload (AoP did not decrease). Obviously, it was mediated by beta-1-receptors, as shown by the attenuation of the beneficial effect of KAS by pretreatment with MET.
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PMID:Effects of the serotonin-antagonist ketanserin on the function of ischaemic and normally perfused myocardium and modification by beta-1-blockade in anaesthetized normotensive dogs. 135 17

The blood-brain barrier (BBB) transport of choline was compared between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar KY rats (WKY). The permeability surface area product (PS) of [3H]choline through the BBB in SHRSP (3.03 X 10(-3) +/- 1.09 X 10(-3) ml/min/g brain) was significantly lower than that in WKY (7.23 X 10(-3) +/- 0.97 X 10(-3) ml/min/g brain) in the presence of respective rat sera. No significant difference in the brain vascular space was indicated from the apparent uptake of [3H]sucrose between SHRSP and SKY. There was no significant difference for the Michaelis constant of choline transport between SHRSP (262 +/- 97 microM) and WKY (180 +/- 32 microM). However, the maximum velocity in SHRSP (3.41 +/- 1.19 nmol/min/g brain) was 37% lower than in WKY (5.40 +/- 0.38 nmol/min/g brain). Brain microdialysis technique was employed to collect the brain interstitial fluid in the rat hippocampus. The concentration of free choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed for the plasma concentration of free choline between SHRSP and WKY. In contrast, no significant difference was observed for the transport of D-[3H]glucose, 3-methyl-[3H]D-glucose and [3H]-phenylalanine through the BBB between SHRSP and WKY. Accordingly, the decreased choline concentration in the brain interstitial fluid ascribed to the specific dysfunction of the BBB choline transport has been demonstrated in SHRSP.
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PMID:Dysfunction of choline transport system through blood-brain barrier in stroke-prone spontaneously hypertensive rats. 234 66

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.
Stroke 1989 May
PMID:Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances. 247 Jan 67

Membrane fractions enriched in sarcoplasmic reticulum (SR) were isolated from the cardiac ventricles of 10-month-old, stroke-prone spontaneously hypertensive rats (SHRSP) which had been maintained for nine months on one of four experimental diets: low protein (LP) (19% protein), standard (STD) (24% protein), high protein (HP) (32% protein), or high methionine (1.9% methionine) (MET). ATPase activities, as well as ATP-dependent Ca2+ binding and Ca2+-uptake activities, of the isolated SR were determined to examine the influence of diet on myocardial Ca2+-pump activity. SR from all four groups exhibited similar Mg2+-ATPase activity. However, the (Ca2+ + Mg2+)-ATPase activity was significantly elevated in SR from rats on the MET diet while the activity in the other groups showed no significant differences. After 15 sec of incubation, Ca2+-uptake (presence of oxalate) in SR from the LP group was significantly less than Ca2+-uptake in SR from each of the three other diet groups. Ca2+ binding (absence of oxalate) in the SR from the LP group was also significantly less than that from each of the three other diet groups. Kinetic analysis of SR Ca2+-uptake over 60 sec revealed that the Bmax of the MET group was significantly higher than Bmax of the STD diet group. In addition, the Bmax of the LP group was significantly lower than Bmax of the HP and MET groups. There was no significant difference in affinity of the SR Ca2+-uptake system among the four diet groups. These results indicate that modification of dietary protein can influence myocardial SR Ca2+-pump function.
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PMID:ATP-dependent calcium uptake in myocardial sarcoplasmic reticulum from spontaneously hypertensive rats: effect of modification of dietary protein. 293 82

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.
Stroke 1988 Oct
PMID:Stable prostacyclin analogue preventing microcirculatory derangement in experimental cerebral ischemia in cats. 265 89

Hypertension is a common finding in patients aged over 60 years, but the following questions need answering. How dangerous is it? Will lowering the blood pressure reduce the attendant risks? What is the 'cost' of such treatment in terms of side effects, drug-induced disease and health service finance? Two recently completed trials throw light on these problems: EWPHE (European Working Party on Hypertension in the Elderly), a European study based on hospital-clinic attenders, using a diuretic backed up with methyldopa; and HEP (randomized trial of treatment of Hypertension in Elderly Patients in Primary Care), based on general-practice screening in England and Wales using atenolol and bendrofluazide. The results of these trials were compared and the findings were broadly similar in the two studies. Some of the differences may be due to the different selection of patients. It is concluded that elderly patients with sustained blood pressures greater or equal to 170/90 mmHg would benefit from treatment by substantial reduction of stroke. Diuretics or beta-blockers, alone or together, are acceptable treatments in elderly subjects.
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PMID:Hypertension in the elderly. 331 29

The plasma concentration of the platelet-specific protein beta-thromboglobulin (beta-TG) was measured in 39 normal subjects and 568 patients of neurological diseases. The beta-TG RIA commercially available KIT was also evaluated. Abnormally high plasma levels of beta-TG were demonstrated in groups of ischemic or obstructive cerebrovascular diseases as compared with that of normal subjects. The highest concentrations were found in 8 patients with Moya-Moya disease, (mean concentration of beta-TG was 204.4 ng/ml), completed stroke at an acute stage was next (mean beta-TG level was 194.8 +/- 70.8 ng/ml). On the other hand, many hemorrhagic cerebro-vascular diseases or other neurological diseases such as brain tumors, hydrocephalus, etc. do not show elevated beta-TG levels. In many patients with ischemic or obstructive cerebro-vascular diseases treated with anti-platelet drugs such as Aspirin, Dipyridamole, Bencyclane or Ticlopidine, a significant fall in plasma concentration of beta-TG was chronologically demonstrated. The measurement of plasma beta-TG concentration may be useful not only in the diagnosis of ischemic or obstructive cerebro-vascular disorders but also in judging the efficacy of anti-platelet therapies and prognosis.
Stroke
PMID:Usefulness of the measurement of plasma beta-thromboglobulin (beta-TG) in cerebrovascular disease. 619 83

Rat hearts were preserved for 18 hr under totally ischemic storage conditions at 0-1 degree C with the commercially supplied EuroCollins, Bretschneider's HTK, and University of Wisconsin (UW) preservation solutions compared with our new preservation solution, Euro-Flush-glutathione solution, and a "refreshed" UW solution (UWG) with 3 mmol/L reduced glutathione added before use. Recovery of the organs was measured during 30 min of parabiotic reperfusion with whole blood of a host rat of the same inbred LEW strain, following an initial warm reflush for 5 min. Functional measurements were performed using a latex balloon in the left ventricle. The metabolic recovery was determined from the myocardium freeze-clamped at the end of reperfusion. The left ventricular pressure (LVP) amplitude during pacing to a heart rate of 300/min, as well as +dp/dtmax, -dp/dtmax, isotonic stroke volume, coronary flow, ATP, and ECP values, recovered significantly better after storage in Euro-Flush-glutathione solution (LVP: 63% of controls on average) compared with when the commercially available solutions were used (EuroCollins: 20%, HTK: 42% of controls in LVP). Hearts preserved in UW solution ViaSpan did not recover during the reperfusion period, when unfiltered solution was used. Filtered ViaSpan resulted in LVP recoveries of 38% of controls, while addition of reduced glutathione immediately before use (UWG) improved the effectivity of this solution significantly (LVP 63% of controls). Similar improvements were found for all other functional and metabolic parameters. Thus, the effectivity of UW solution ViaSpan depends upon extraction of the typical particles by a filtering procedure. Effectivity can be improved by a refreshment procedure with reduced glutathione immediately before use.
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PMID:Effectivity of freshly prepared or refreshed solutions for heart preservation versus commercial EuroCollins, Bretschneider's HTK or University of Wisconsin solution. 776 58

The effects of the endogenous pressor agents noradrenaline (NA), and angiotensin II (Ang II), and of the hypotensive agents acetylcholine (ACh) and adenosine (ADS), on blood pressure and heart rate in conscious and unrestrained stroke-prone spontaneously hypertensive rats (SHR-SP) and normotensive Wistar Kyoto rats (WKY) of different ages (4-9 weeks old) were investigated. Pressor responses to NA were enhanced in 7- and 9- week-old SHR-SP compared with those in WKY, but pressor responses to Ang II in SHR-SP were not different from those in WKY at all ages. The bradycardias following pressor responses to NA and Ang II were markedly attenuated in SHR-SP, especially older ones. Hypotensive responses to ACH were enhanced in SHR-SP, particularly at 9 weeks of age. However, hypotensive responses to ADS were attenuated in SHR-SP, especially at 7 weeks of age. Transient fall of heart rate due to ADS was also attenuated in 7- and 9- week-old SHR-SP. These alterations of hemodynamic or cardiovascular responses in SHR-SP became more evident in the established stages of hypertension. These results suggest intimate relationships of the enhanced pressor responses to NA, attenuated bradycardias following pressor effects with NA or Ang II, and the attenuated hypotensive responses to ADS with the development or the maintenance of hypertension in SHR-SP.
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PMID:Studies of cardiovascular responses to some endogenous pressor and hypotensive agents in conscious stroke-prone spontaneously hypertensive rats of different ages. 824 50

Several studies have demonstrated an increased risk of cardiovascular disease (CVD) in relation to high blood pressure in elderly patients aged below 70-75, whereas the risk seemed to decline with age in the older elderly. Early studies on the effect of treatment of mild to moderate hypertension in the elderly indicated (but did not convincingly show) a reduction of CVD. In the 1980s, both the EWPHE trial (European Working Party on High Blood Pressure in the Elderly) and the HEP study (The Randomised Trial of the Treatment of Hypertension in Elderly Patients in Primary Care) provided evidence of the benefit of treating high blood pressure in the elderly, at least up to the age of 70-74. These results have lately been confirmed by three major trials SHEP (Systolic Hypertension in the Elderly Program), STOP (Swedish Trial in Old Patients with Hypertension) and MRC (Medical Research Council), also including older patients (STOP) and those with isolated systolic hypertension (SHEP). This satisfactory effect was not impaired by a low tolerability of the drugs used (beta-blockers and diuretics). In conclusion, drug treatment with beta-blockers and diuretics in hypertensive men and women aged 70 and above confers highly significant and clinically relevant reductions in cardiovascular (especially stroke) morbidity and mortality. The clinical implication of this is that blood pressure lowering therapy should be considered in elderly hypertensives, at least up until they are 80. It should also be remembered that elderly hypertensives often have other diseases as well and that the drug treatment should be adjusted accordingly.
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PMID:Hypertension in the elderly. 826 94


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