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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies have shown that angiotensin-converting enzyme (ACE) inhibitor treatment in young genetically hypertensive rats prevents the full expression of blood pressure and vascular abnormalities in the adult. This model provides unique conditions with which to study the pathogenesis of altered Ca++ regulation. Normotensive (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) received at 6 to 10 weeks of age either ACE inhibitor (ramipril), hydralazine/hydrochlorothiazide or no treatment. At 17 weeks of age, rats were anesthetized, and vascular tissue was excised. Thoracic aorta challenged with 20 mM caffeine in Ca(++)-free buffer produced a phasic contractile response. The magnitude of this phasic response was used as a measure of Ca++ released from intracellular stores; a direct correlation between this phasic response and systolic blood pressure was observed. A concentration-response curve to Bay K8644 was performed on carotid arteries; a direct correlation of force development to Bay K8644 and systolic blood pressure was observed. All WKY groups showed lower blood pressure and force development in response to Bay K8644 than did SHRSP. Treatment with ramipril reduced blood pressure and force development in response to Bay K8644 in adult SHRSP, although not to levels of WKY rats, whereas WKY rats were unaffected by treatment. These data support the hypothesis that contractile responses to Bay K8644 in carotid arteries and caffeine in aorta parallel changes in systolic blood pressure. We conclude that alteration of Ca++ regulation in hypertension is directly related to elevated blood pressure and mediated by an angiotensin II-sensitive mechanism during development.
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PMID:Angiotensin-converting enzyme inhibition during development alters calcium regulation in adult hypertensive rats. 750 33

The central nervous system myelin basic protein (MBP) stimulates the release of several peptide hormones including insulin and glucagon. This could be associated with the development of hyperglycaemia in neurological disorders such as stroke, in which MBP is known to leak into blood circulation. In the present study the mechanism of insulin and glucagon release was investigated by using short-term incubation of isolated rat pancreatic islets. Incubation with MBP in the absence of Ca2+ resulted in approx. 11-fold stimulation of insulin and glucagon release. The stimulation dwindled with increasing Ca2+ concentration and was 6.5-fold at 0.5 mM and 2-fold at 2.5 mM Ca2+. When MBP and glucose at various concentrations were simultaneously present in the incubation mixture, stimulation of insulin release was the sum of the stimulation induced by these two agents separately both at the 0.5 and 2.5 mM Ca2+ concentrations. Glucose at concentrations of 10 or 15 mM did not suppress MBP-stimulated glucagon release. Caffeine-evoked increase in intracellular Ca2+ was without effect on MBP-stimulated insulin or glucagon release but enhanced glucose-induced insulin release. The Ca2+ channel blocker diltiazem had no effect on MBP-stimulated insulin release at concentrations where glucose-stimulated release was inhibited. Ruthenium red inhibited both MBP- and glucose-stimulated insulin release as well as MBP-induced glucagon release. Staurosporine (inhibitor of protein kinase C) had no effect on MBP-induced insulin release, although it partially inhibited glucose-stimulated release. Maleylation of MBP abolished its insulin- and glucagon-releasing activity by approx. 90%. These results suggest that MBP exerts its insulin-releasing effect by mechanisms different from those of glucose-stimulated insulin release and does not require Ca2+ channels or protein kinase C. The relation of MBP-induced insulin and glucagon release to Ca2+ concentration is probably explained by enhanced self-aggregation of MBP or by increased ability of MBP to interact with islet cell membranes in the absence of Ca2+, or both. It is concluded that MBP-induced hormone release appears to be mediated by membrane fusion and oligomerization of MBP. The mechanism thus resembles that of various toxins and other cytotoxic agents.
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PMID:Mechanism of the myelin basic protein-induced insulin and glucagon release from isolated rat pancreatic islets. 754 15

Myocardial contractile performance is a function of sarcoplasmic reticular Ca2+ uptake and release. Ca2+ handling is ATP-dependent and can account for up to 40% of total myocardial energy expenditure. We tested the hypothesis that the thermodynamics of the cytosolic adenylate system can modulate sarcoplasmic reticular Ca2+ handling and hence function in intact heart. Cellular energy level was experimentally manipulated by perfusing isolated working guinea-pig hearts with substrate-free medium or media fortified with lactate and/or pyruvate as the main energy substrate. Left ventricular contractile function was judged by stroke work and intraventricular dP/dt. Cytosolic energy level was indexed by measured creatinine kinase reactants. Relative to 5 mM lactate, 5 mM pyruvate increased left ventricular stroke work, dP/dtmax, and dP/dtmin, while lowering left ventricular end-diastolic pressure at physiological left atrial and aortic pressures. Pyruvate also doubled cytosolic phosphorylation potentials and increased [ATP]/[ADP] ratio; this energetic enhancement distinguishes pyruvate from inotropic stimulation by catecholamines, which are known to decrease cytosolic energy level in perfused heart. Sarcoplasmic reticular Ca2+ handling was assessed in hearts prelabeled with 45Ca, subjected to 45Ca washout in the presence of different cytosolic energy levels, then stimulated with 10 mM caffeine to release residual sarcoplasmic reticular 45Ca. When ryanodine (1 microM) was applied to open Ca2+ channels and thereby released 45Ca from the sarcoplasmic reticulum during washout, caffeine-stimulated 45Ca release was decreased 96%, demonstrating that virtually the entire caffeine-sensitive 45Ca pool was located in the sarcoplasmic reticulum. In detailed comparisons of pyruvate-energized vs. substrate-free deenergized hearts, an inverse relationship between cytosolic energy level and caffeine-mobilized 45Ca pool size was observed. Thus, caffeine-induced 45Ca release was decreased 60% by pyruvate energization and increased 2.5-fold by substrate-free deenergization. Taken together, these results support the hypothesis that enhancement of myocardial inotropism by energy-yielding substrate is mediated by increased sarcoplasmic reticular Ca2+ loading/release. Thus we propose that the known control of sarcoplasmic reticular Ca2+ turnover by the protein kinase/phospholamban system can be modulated by cytosolic energy level.
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PMID:Energetic modulation of cardiac inotropism and sarcoplasmic reticular Ca2+ uptake. 794 40

The pathological findings in 165 patients explored for malignant hyperthermia (MH) susceptibility are reported. The first group of 120 subjects were patients investigated for MH. These patients had suffered an attack of MH under anaesthetic or were members of families in which a subject had died of MH. In vitro contracture tests revealed 25 malignant hyperthermia susceptible (MHS) subjects, with positive contracture tests for halothane and caffeine, 5 malignant hyperthermia subjects with reaction to caffeine only (MHC), 3 malignant hyperthermia subjects with reaction to halothane only (MHH) and 87 malignant hyperthermia negative (MHN) subjects with normal contracture tests. The second group of 45 subjects had exertional heat stroke. In vitro contracture tests performed at least 3 months after the exertional heat stroke revealed 11 MHS, 6 MHC, 2 MHH subjects and 26 MHN. In both groups, whatever the in vitro contracture test results, pathological findings were heterogeneous and revealed various changes: rhabdomyolysis, mitochondrial myopathy, denervation, type II atrophy, AMPase deficiency, non-specific findings or normal features. Central core myopathy was only observed in the first subgroup and was the only disease significantly associated with MH. In contrast to previous reports, this study demonstrates the absence of a specific malignant hyperthermia or exertional heat stroke myopathy. Furthermore, the discovery of MHS subjects among the EHS group of patients highlights the need for systematic exploration of all these patients.
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PMID:Pathological findings in 165 patients explored for malignant hyperthermia susceptibility. 818 10

This paper illustrates the use of impedance cardiography in an applied research setting to examine some of the pharmacological effects of caffeine on cardiovascular function. A primary advantage of the technique was in providing a noninvasive approach for studying cardiac versus vascular mechanisms underlying blood pressure responses to acute caffeine challenge. Impedance cardiography allowed the quantification of stroke volumes and cardiac output, and the change in these variables over time in a within-subjects design. Systemic vascular resistances were then calculated when impedance data were combined with simultaneously measured blood pressures. Results from four studies are summarized in which caffeine significantly elevated systolic and diastolic blood pressures. Impedance-derived measures indicate that caffeine's pressor response can be attributed to increased systemic vascular resistance rather than to elevated cardiac output. Our findings were consistent across all four studies, and across all protocols within those studies. Furthermore, these response patterns were confirmed by obtaining similar results using nuclear ventriculography. Thus, with respect to the outcome of testing an applied question, impedance-derived findings were found to be reliable and valid when compared with another technique used more commonly in clinical settings.
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PMID:Consistency of cardiovascular response pattern to caffeine across multiple studies using impedance and nuclear cardiography. 821 19

Acute ethanol exposure (8-570 mM) induced potent contractile responses of rings in both basilar and middle cerebral arteries, from dogs, sheep, piglets and baboons, in a dose-dependent manner. The contractions were reproducible and not tachyphylactic. The middle cerebral arteries were found to be more sensitive to ethanol than the basilar arteries. No known pharmacological antagonist, tested, exerted any effects on ethanol-induced contractions. No differences in responsiveness to ethanol in canine cerebral arteries were found between male and female animals or between the presence and the absence of endothelial cells. Removal of extracellular Ca2+ ([Ca2+]o) partially attenuated ethanol-induced contractions, while withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated such contractions. In the complete absence of [Ca2+]o, caffeine and ethanol induced similar, transient contractions followed by relaxation in K(+)-depolarized cerebral vascular tissue. Ethanol-induced contractions were completely abolished by pretreatment of tissues with caffeine. Our results suggest that: (a) acute ethanol intoxication can induce direct contractions (independent of amine, prostanoid or opioid mediation) of diverse mammalian cerebral vascular tissues, including those from primates; (b) these contractile responses are heterogeneous along the cerebrovascular tree and independent of endothelial cells; (c) in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for ethanol to induce contractions; and (d) hypomagnesemia or Mg deficiency potentiates the contractile effects of ethanol on brain vessels and may be a risk factor for ethanol-related, ischemic stroke events.
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PMID:Ethanol-induced contraction of cerebral arteries in diverse mammals and its mechanism of action. 829 88

A 37 year-old man with an ischaemic stroke after the nasal use of amphetamine and caffeine is reported. Transient arterial hypertension due to these agents may have been the mediator of the stroke. Mitral annular calcification was the only other abnormality found, and was thought not to play an important role in this patient. There was no evidence of a primary or secondary hypercoagulable state. Stroke due to nasal use of these agents appears not to have been previously reported (Medline literature search 1983-1993).
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PMID:Intranasal caffeine and amphetamine causing stroke. 834 3

OBJECTIVE--To assess the relationship between coffee consumption and risk of coronary heart disease (CHD) among women. DESIGN--Prospective cohort study with coffee consumption measured in 1980, 1984, and 1986, and follow-up through 1990. SETTING--Female registered nurses in the United States. PARTICIPANTS--A total of 85,747 US women 34 to 59 years of age in 1980 and without history of CHD, stroke, or cancer. MAIN OUTCOME MEASURE--Ten-year incidence of CHD (defined as nonfatal myocardial infarction or fatal CHD). RESULTS--During 10 years of follow-up we documented 712 cases of CHD. After adjustment for age, smoking, and other CHD risk factors, we found no evidence for any positive association between coffee consumption and risk of subsequent CHD. For women drinking six or more cups of caffeine-containing coffee per day in 1980, the relative risk was 0.95 (95% confidence interval, 0.73 to 1.26) compared with women who did not consume this beverage. Similarly, there was no association when the first 4 years of follow-up were excluded, when nonfatal and fatal CHD end points were examined separately, or when we updated coffee consumption in 1984 or 1986 and examined only CHD during the next 2-year interval. Further, there was no association with caffeine intake from all sources combined or with decaffeinated coffee consumption. CONCLUSIONS--These data indicate that coffee as consumed by US women is not an important cause of CHD.
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PMID:Coffee consumption and coronary heart disease in women. A ten-year follow-up. 862 67

1. The purpose of the present study was to develop an experimental strategy for the quantification of the cardiovascular effects of non-selective adenosine receptor ligands at the adenosine A1 and A2a receptor in vivo. 2-Chloroadenosine (CADO) was used as a model compound. 2. Three groups of normotensive conscious rats received an short intravenous infusion of 1.4 mg kg-1 CADO during constant infusions of the A1-selective antagonist, 8-cyclopentyltheophylline (CPT; 20 micrograms min-1 kg-1), the A2a-selective antagonist, 8-(3-chlorostyryl) caffeine (CSC; 32 micrograms min-1 kg-1) or the vehicle. The heart rate (HR) and mean arterial blood pressure (MAP) were recorded continuously during the experiment and serial arterial blood samples were taken for analysis of drug concentrations. The ratio MAP/HR was also calculated, which may reflect changes in total peripheral resistance on the assumption that no changes in stroke volume occur. 3. During the infusion of CPT, CADO produced a reduction in both blood pressure and MAP/HR by activation of the A2a receptor. The concentration-effect relationships were described according to the sigmoidal Emax model, yielding potencies based on free drug concentrations (EC50,u) of 61 and 68 ng ml-1 (202 and 225 nM) for the reduction of blood pressure and MAP/HR, respectively. During the infusion of CSC, an EC50,u value of 41 ng ml-1 (136 nM) was observed for the A1 receptor-mediated reduction in heart rate. The in vivo potencies correlated with reported receptor affinities (Ki(A1) = 300 nM and Ki(A2a) = 80 nM). The maximal reductions in MAP/HR and heart rate were comparable to those of full agonists, with the Emax values of -12 +/- 1 x 10(-2) mmHg b.p.m.-1 and -205 b.p.m. respectively. 4. It is concluded that this integrated pharmacokinetic-pharmacodynamic approach can be used to obtain quantitative information on the potency and intrinsic activity of new non-selective adenosine receptor agonists at different receptor subtypes in vivo.
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PMID:Pharmacokinetic-haemodynamic relationships of 2-chloroadenosine at adenosine A1 and A2a receptors in vivo. 873 40

Cerebral ischemia of 5 min duration was induced in unanesthetized Mongolian gerbils by bilateral occlusion of the carotid arteries. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity following ischemia and by a histopathological assessment of the extent of CA1 hippocampal pyramidal cell injury and loss 5 days after ischemia. The A2a adenosine receptor selective antagonists 8-(3-chlorostyryl) caffeine (CSC; 0.1 mg/kg i.p.) and 4-amino-1-phenyl[1,2,4]-triazolo[4,3-a] quinoxaline (CP 66,713; 0.1 mg/kg i.p.) reduced the extent of ischemia-induced injury. An A1 selective receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1.0 mg/kg i.p.), enhanced ischemia-evoked injury. These results suggest that adenosine A2a receptor antagonists may be useful for the prevention of cerebral injuries resulting from stroke or cardiac arrest.
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PMID:The effects of selective A1 and A2a adenosine receptor antagonists on cerebral ischemic injury in the gerbil. 882 36


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