Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukotriene (LT) release from vascular and pulmonary tissue was assessed by a radioimmunoassay for peptide leukotrienes (i.e., LTC4, LTD4 and LTE4). The calcium ionophore A-23187 at 1-3 micrograms/ml and platelet activating factor (PAF) at 10 micrograms/ml produced marked formation of peptide leukotrienes in minced cat pulmonary tissue. This was also confirmed by bioassay of the incubates in isolated perfused cat coronary arteries. Rat pulmonary tissue was comparable to cat with regard to LT production, but guinea-pig lung produced about 30-50% less on a weight basis. In addition, aortic and coronary artery vessel walls produced significant amounts of LTs. The time course for maximal leukotriene production occurred at 45-60 min of incubation at 37 degrees C in both the radioimmunoassay and the bioassay. Cat coronary artery constricted markedly to LTC4 or LTD4 (30-40 mm Hg) and to the lung or blood vessel incubate. This constriction was virtually totally blocked by the leukotriene antagonist FPL-55712, but not by the thromboxane receptor antagonist, pinane thromboxane A2, the alpha-adrenergic receptor antagonist, phenoxybenzamine, or the angiotensin receptor antagonist, saralasin. Thus, pulmonary and vascular tissue produce leukotrienes that appear to exert coronary constrictor effects on specific leukotriene receptors. These results indicate that the ischemia of shock and anaphylaxis may be accentuated by the release of peptide leukotrienes.
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PMID:Potentiation of leukotriene formation in pulmonary and vascular tissue. 608 2

The cause of noise-induced hearing loss remains unclear despite years of both epidemiologic and experimental investigation. Among the many possible pathophysiologic mechanisms that may contribute to noise-induced temporary or permanent threshold shifts are insufficiencies in cochlear blood flow. Although the literature is inconsistent, several histologic and physiologic studies demonstrate signs of reduced circulation in the cochlea after noise exposure. Recent studies using computer-enhanced intravital microscopy complement these earlier findings. Evidence suggests that these microcirculatory events are mediated in part by several circulating factors, including the potent vasoactive peptide angiotensin. This study investigated this possibility by pretreating with the angiotensin receptor antagonist sarthran during noise exposure and examining both cochlear microcirculation and auditory sensitivity. The results of these experiments show noise-induced ischemia in the lateral wall of the cochlea and temporary threshold shifts. Treatment with sarthran prevented this noise-induced microcirculatory ischemia and preserved auditory sensitivity at the low frequencies tested. These findings support a role for the angiotensinergic system during noise exposure and suggest that preservation of cochlear blood flow is functionally related to auditory sensitivity.
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PMID:Sarthran preserves cochlear microcirculation and reduces temporary threshold shifts after noise exposure. 959 53

MRI myocardial tagging is now a well-developed method for evaluation of regional myocardial contraction. A series of progressively more refined imaging strategies, combined with advances in analytic strategies have provided a strong armamentarium of methods. Important insights into normal human physiology of left ventricular systolic and diastolic function have been developed using one-dimensional, two-dimensional and three-dimensional analyses of myocardial deformation. In disease states, improved understanding and detection of early alterations in myocardial function in hypertensive heart disease has been possible. In addition, improved understanding of effects of ischemia and infarction on regional function has been possible. Further, after acute myocardial infarction, clearer definition of the natural history of contractile dysfunction in the infarct region and the zone adjacent to the infarct have been possible. Similarly, effects on regional function of a number of important pharmacologic agents used for treatment, such as angiotensin converting enzyme inhibitors, beta blockers and angiotensin receptor blockers have been characterized. In the cardiomyopathies, myocardial tagging has permitted more reliable assessment of heterogeneity of segmental function, especially in hypertrophic cardiomyopathy. Finally, initial applications of myocardial tagging to assessment of right ventricular regional function in hypertrophied hearts with and without major congenital abnormalities have generated advances in understanding of effects of hypertrophy on right ventricular function.J. Magn. Reson. Imaging 1999;10:609-616.
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PMID:MRI myocardial tagging. 1054 69

Angiotensin II (Ang II) and apoptosis contribute significantly to myocardial ischemia-reperfusion (I-R) injury. Evidence indicates that Ang II may activate apoptosis in myocytes. The present study was undertaken to investigate the effects of angiotensin receptor blockers (ARBs), candesartan, on the apoptosis of cardiac myocytes in rats after I-R. Rats were divided into a control group, a candesartan group I (0.015 mg/kg), and a candesartan group II (0.03 mg/kg). Candesartan was intravenously administered 30 min before ischemia. All rats were subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The data showed that left ventricular (LV) systolic pressure and LV +dp/dt was decreased after administration of candesartan, but increased after reperfusion in the candesartan group II, compared with those in the candesartan group I and control group. LV -dp/dt was decreased after candesartan administration in candesartan group II. The number of apoptotic cells in the candesartan groups (497+/-204 and 543+/-254, respectively) was higher than that in the control group (287+/-166; p<0.05). There was no significant difference in infarct size among the three groups. However, plasma CPK was lower in the candesartan groups than in the control group. Northern blot analysis showed that p53 mRNA was upregulated in the candesartan groups, in association with increased expression of bax mRNA. Immunohistochemical analysis showed that p53 and bax immunoreactivity were increased in both of the candesartan groups. In conclusion, candesartan increased apoptosis in the rat hearts after acute I-R, and this increase was possibly mediated by upregulation of p53 and bax gene expressions. In addition, candesartan was shown to improve LV function, in association with reduction of CPK release.
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PMID:An angiotensin II type 1 receptor blocker, candesartan, increases myocardial apoptosis in rats with acute ischemia-reperfusion. 1140 58

Disruption of any one of a large number of balanced systems that maintain cardiomyocyte structure and function can cause myocardial dysfunction. Such disruption can occur either in response to acute stresses such as cardiac surgery with cardiopulmonary bypass and cross-clamping of the aorta or because of more chronic stresses resulting from factors such as genetic abnormalities, infection, or chronic ischemia. Several currently available therapies such as beta-adrenergic receptor agonists and antagonists, phosphodiesterase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other agents affect cardiomyocytes in ways that are more far reaching than initially appreciated when these agents were first introduced into clinical practice. As our knowledge and understanding of myocardial dysfunction increases, particularly in the neonatal and pediatric patient, we will be able to further target interventions to highly specific perturbations of cellular function and individual genetic variability.
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PMID:Cellular and molecular aspects of myocardial dysfunction. 1159 64

Congestive heart failure (CHF) is associated with an impaired flow-mediated vasodilation that reflects an impaired endothelial function. Limited information is available, however, on whether and to what extent this impairment is improved by pharmacological or nonpharmacological treatment. We measured radial artery diameter and blood flow by an echo-tracking Doppler device both at baseline and after 4 minutes of hand ischemia, which increases diameter through NO secretion mediated by an increase in flow and shear stress. Data were collected from 44 CHF patients (New York Heart Association class I to III) under standard treatment (diuretic, digitalis, and enalapril, 20 mg/d), in whom CHF severity was assessed by a cardiopulmonary stress test, and from 16 age- and sex-matched controls. CHF patients were then randomized to maintain for (A) 2 months of standard treatment (n=11), (B) treatment with double the ACE inhibitor dose (n=11), (C) standard treatment with an angiotensin II antagonist (losartan, 50 mg/d; n=11), or (D) standard treatment with bicycle training for 30 minutes, 3 times a week (n=11). At baseline, radial artery diameter and flow were similar in CHF patients and controls; CHF patients had a modest although significant impairment in flow increase (-36%) and a striking impairment (-78%) in diameter increase following the 4 minutes of ischemia. After 2 months, baseline diameter and flow remained unaltered in the 4 groups. After the 4 minutes of ischemia, radial artery flow and diameter increased as before in the group under standard treatment (A), whereas in the other 3 groups, the increase was significantly (P<0.05) and, for diameter, markedly (B, 83%; C, 92%; and D, 95%) greater. The vasodilatation induced by trinitroglycerin was similar in CHF and control subjects and not affected by treatments. In CHF, radial artery shows a marked reduction in flow-mediated vasodilation, reflecting impairment of endothelial function. This impairment can be markedly improved by treatments that effectively block the renin-angiotensin system either at ACE or at ACE plus angiotensin receptor level. This is the case also with nonpharmacological treatment of CHF.
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PMID:Radial artery flow-mediated dilatation in heart failure patients: effects of pharmacological and nonpharmacological treatment. 1175 34

Based on the data from large single and multi-center clinical trials, including the Heart Outcomes Prevention Evaluation (HOPE) study, it is clear that the presence of microalbuminuria is a signal from the kidney that cardiovascular risk is increased and that vascular responses are altered. This is exemplified by studies that have demonstrated that the compensatory vasodilation seen following relief from prolonged ischemia or infusion of vasodilators such as nitroglycerin is blunted in people with microalbuminuria. Thus, the presence of between 30 and 299 mg/day of albumin in the urine is associated with abnormal vascular responsiveness, which may be the result of more advanced atherosclerosis and not necessarily related to the presence of hypertension or renal disease. Agents known to reduce the rise in microalbuminuria or actually reduce the level of microalbuminuria, such as ACE inhibitors, angiotensin receptor blockers, HMG-CoA reductase inhibitors, beta blockers, non-dihydropyridine calcium channel blockers and diuretics, have all been shown to reduce cardiovascular mortality and in some cases preserve renal function. This article will present an overview of the data that support the assertion that a reduction in the rise of microalbuminuria is a significant consideration in the selection of agents to treat a given risk factor (cholesterol or blood pressure) to a recommended target goal. Achieving such a goal with agents that also impact microalbuminuria will provide for a more complete cardiovascular risk reduction.
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PMID:Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. 1208 33

Heart failure is a leading cause of hospital admissions in North America. Approximately half of patients with symptoms of heart failure have normal or minimally impaired systolic function and are therefore diagnosed, by exclusion, with diastolic dysfunction. The therapy of diastolic dysfunction to date is largely unsatisfactory. There have been few outcome-based clinical trials to guide clinicians, and most treatments have been empirically derived from the data from systolic heart failure studies. In general, acute management consists of central volume reduction with loop diuretics and long-acting nitrates. In some cases improvement in left ventricular filling can be achieved by reducing heart rate, usually with either beta blockers or calcium channel blockers. The role of digoxin is unclear and it should be used with caution. Theoretically, it has the capacity to further impair ventricular function, but one of the few trials in diastolic heart failure suggested that it improves symptoms and reduces hospitalization. Renin-angiotensin system blockade is a very attractive therapeutic avenue; angiotensin-converting enzyme inhibitors and angiotensin receptor blockers effectively reduce afterload, induce regression of left ventricular hypertrophy in excess of their blood pressure-lowering effect, and confer survival benefits to patients at high risk for cardiovascular death. Although the results of a recent trial using an angiotensin receptor blocker in patients with primarily diastolic heart failure were unimpressive, renin-angiotensin system blockade should still be considered because of its aforementioned benefits. The long-term management of these patients includes a careful assessment for and treatment of myocardial ischemia, treatment of hypertension, and reduction in left ventricular hypertrophy. For the treatment of ischemia, long-acting nitrates and calcium channel blockers may be particularly useful. The results of new trials in this area are expected soon, and hopefully therapy that directly targets the pathophysiologic pathways of this important disease is on the horizon.
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PMID:Diastolic Dysfunction. 1502 85

Besides cyclooxygenase and NO-synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization (EDHF), is involved in the relaxation of the vascular smooth muscle cells. EDHF has been demonstrated unequivocally in various blood vessels from different species, including human, and is likely to play an important role in cardiovascular physiology. This alternative pathway involves the activation of two populations of endothelial potassium channels, the small conductance and intermediate conductance calcium-activated potassium channels (SK(Ca) and IK(Ca), respectively). EDHF-mediated responses are clearly altered in various pathological conditions (ageing, hypertension, atherosclerosis, hypercholesterolemia, heart failure, ischemia-reperfusion, angioplasty, eclampsia, diabetes, sepsis). Therapeutic or adjutant interventions (angiotensin converting enzyme inhibitors, antagonist of the angiotensin receptor, estrogen, omega-3 polyunsaturated fatty acids, polyphenol derivatives, potassium and/or calcium intake) can restore these responses, suggesting that the improvement of the EDHF pathway contributes to the observed beneficial effect of these various substances. However, the improvement or restoration of EDHF responses has not been, yet, the direct purpose of any pharmaceutical effort. Activating endothelial IK(Ca) and/or SK(Ca) or increasing their expression as well as improving myo-endothelial communication, for instance by increasing the expression of connexin(s), could become interesting therapeutic targets.
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PMID:EDHF: new therapeutic targets? 1502 34

Several large clinical trials have demonstrated that successful control of blood pressure decreases the incidence of strokes. Also, drugs that stimulate the production of angiotensin II, such as diuretics, calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs), provide additional stroke reduction than drugs that suppress angiotensin II production such as beta-blockers and angiotensin converting enzyme (ACE) inhibitors. Since the stroke-protective effect of angiotensin II is mediated through stimulation of the AT2 receptors, drugs that selectively block the AT1, such as the ARBs, provide greater stroke protection than the other antihypertensive drugs. The blockade of the AT1 receptors lessens local brain ischemia, whereas the stimulation of the AT2 receptors increases local blood flow through recruitment of collateral vessels. Among the ARBs, losartan possesses certain unique properties not shared by other members of its class, which enhance its stroke-protective effects. These include the prevention of platelet adhesiveness and aggregation and the decrease of serum uric acid levels, which both lead to reduction in cardiovascular and cerebrovascular events. (
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PMID:Stroke prevention with losartan in the context of other antihypertensive drugs. 1553 51


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