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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of renal ischemia with reperfusion on the reactivity of rabbit renal vasculature. The main renal and arcuate arteries were isolated and studied as ring preparations. In the renal artery, concentration-response curves for potassium chloride (KCl), noradrenaline (NA), serotonin (5-HT), angiotensin II (AII), acetylcholine (ACh), A23187 or sodium nitroprusside (SNP) were unaltered after ischemia and reperfusion. Under the same conditions, the relaxation of arcuate arteries elicited by ACh was reduced when vessels were precontracted with methoxamine but not with KCl, whereas SNP-induced responses were unaffected. In anesthetized rabbits, renal blood flow and corresponding renal vascular resistances (RVR) were not modified by ischemia and reperfusion. ACh (1, 3 and 10 micrograms/kg per min) reduced RVR (maximally -24 +/- 8%) and this response was unchanged after ischemia and reperfusion (maximally -25 +/- 10%). These results demonstrate that the rabbit renal vasculature is relatively resistant to an ischemic insult and is probably not involved in the development of postischemic renal failure.
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PMID:Endothelium-dependent control of vascular tone in the rabbit kidney after ischemia and reperfusion. 845 77

The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle cells. Monoaminooxidase deactivates catecholamines and serotonin. Angiotensin converting enzyme transforms angiotensin I into angiotensin II and breaks down bradykinin into inactive products. Nitric oxide is a potent vasodilator and inhibitor of platelet function that under most circumstances is released together with prostacyclin, which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin-1, thromboxane A2, and endoperoxides. Endothelium-derived growth inhibitors include heparin (sulfates) and transforming growth factor beta 1, while basic fibroblast growth factors and platelet-derived growth factor and possibly endothelin promote proliferation. Because of its strategic anatomic position, the endothelium is a primary target for injuries and cardiovascular risk factors. In particular, aging, low density lipoproteins, hypertension, diabetes, and ischemia alter endothelium function. In arterial coronary bypass grafts, the release of nitric oxide is more pronounced than in vein grafts. Alterations of endothelial function may contribute to vasospasm, thrombus formation, and vascular proliferation and in turn myocardial ischemia, all common events in patients with coronary artery disease.
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PMID:Endothelial dysfunction in coronary artery disease. 847 60

Potent vasoconstrictors such as angiotensin II and vasopressin have been implicated as mediators of persistent vasoconstriction after reversible superior mesenteric artery (SMA) occlusion. Neither captopril (CAP), an angiotensin-converting enzyme (ACE) inhibitor, nor papaverine (PAP), a vasodilator, has proven effective in reversing this vasoconstriction when employed singly. The present study examined the combined effect of these agents in reducing mortality in a murine model of acute mesenteric ischemia. The SMAs of 106 adult male Sprague-Dawley rats were totally occluded for 85 minutes. Test agents were given intravenously at reperfusion over a 90-minute period. Survival rates were assessed at 48 hours. CAP was given as a single bolus (0.3 mg/kg) and PAP (0.5 mg/kg/h) as an infusion. Aortic and SMA blood flows were measured pretreatment and posttreatment in a separate group of 19 animals treated with CAP and PAP as single agents. chi 2 analysis and analysis of variance were used to test differences with p < or = 0.05 accepted as significant. PAP alone as an adjunct resulted in a significant increase in 48-hour survival (57% versus 19%, p < or = 0.005). PAP in combination with CAP produced the best outcome in this model (87% versus 19%, p < or = 0.005). Aortic blood flow decreased, whereas SMA blood flow increased after treatment both with CAP and with PAP, but not significantly. The combination of an intravenously administered vasodilator with either glucagon or an ACE inhibitor was the most effective adjunctive therapy in this mesenteric ischemia model. There was no evidence that an inotropic effect, rather than SMA vasodilation, was the responsible mechanism of action.
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PMID:Adjunctive vasodilator therapy in the treatment of murine ischemia. 850 68

A growing body of evidence supports the notion that calcium antagonists exert a renal protective effect. Calcium antagonists may play an important future role in renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemia or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast media, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Such protection may extend to favorably influencing the course of chronic renal insufficiency, particularly when the latter is complicated by hypertension. Seven putative mechanisms have been proposed by which calcium antagonists may ameliorate the decline in GFR associated with renal insufficiency. These are: (a) reduction in blood pressure per se, (b) reduction in renal hypertrophy, (c) modulation of mesangial traffic of macromolecules, (d) reduction in metabolic activity in remnant renal tissue, (e) amelioration of uremic nephrocalcinosis, (f) reduction of pressure-induced calcium entry into vessel walls, and (g) reduction of free radical formation. Experimental investigations in rats with reduced renal mass, desoxycorticosterone-induced hypertension, or chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view.
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PMID:Calcium antagonists and renal protection. 851 90

Left ventricular hypertrophy is considered to be an independent risk factor giving rise to ischemia, arrhythmias, and left ventricular dysfunction. Slow movement of intracellular calcium contributes to the impaired contraction and relaxation function of hypertrophied myocardium. Myofibril content may also be shifted to fetal-type isoforms with decreased contraction and relaxation properties in left ventricular hypertrophy. Myocyte hypertrophy and interstitial fibrosis are regulated independently by mechanical and neurohumoral mechanisms. In severely hypertrophied myocardium, capillary density is reduced, the diffusion distance for oxygen, nutrients, and metabolites is increased, and the ratio of energy-production sites to energy-consumption sites is decreased. The metabolic state of severely hypertrophied myocardium is anaerobic, as indicated by the shift of lactate dehydrogenase marker enzymes. Therefore, the hypertrophied myocardium is more vulnerable to ischemic events. As a compensatory response to severe cardiac hypertrophy and congestive heart failure, the ADP/ATP carrier is activated and atrial natriuretic peptide is released to increase high-energy phosphate production and reduce cardiac energy consumption by vasodilation and sodium and fluid elimination. However, in severely hypertrophied and failing myocardium, vasoconstrictor and sodium- and fluid-retaining factors, such as the renin-angiotensin system, aldosterone, and sympathetic nerve activity, play an overwhelming role. Angiotensin-converting enzyme inhibitors (ACEIs) are able to prevent cardiac hypertrophy and improve cardiac function and metabolism. Under experimental conditions, these beneficial effects can be ascribed mainly to bradykinin potentiation, although a contribution of the ACEI-induced angiotensin II reduction cannot be excluded.
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PMID:Substrate metabolism, hormone interaction, and angiotensin-converting enzyme inhibitors in left ventricular hypertrophy. 852 2

After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin-prostaglandin-nitric oxide pathway, not inhibition of angiotensin II formation.
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PMID:Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats. 859 91

Nitrates have been widely used for the treatment of patients with chronic congestive heart failure. Although the use of these drugs has not been evaluated by large-scale studies traditionally used for evaluation of new therapy, multiple studies over the years have demonstrated their favorable effects. Organic nitrates have been shown to have a beneficial effect on ischemia, hemodynamic profile, magnitude of mitral regurgitation, endothelial function, and cardiac remodeling. These drugs alone or in combination with hydralazine have improved exercise capacity, maximal oxygen consumption, cardiac function, and survival. The use of nitrates in patients with heart failure has been limited by reduced responsiveness (resistance) and early development of tolerance. Nitrate resistance is due to reduced vascular response and results in the need to use a larger dose of any nitrate preparation when used for the treatment of patients with heart failure compared to patients without heart failure. Recent information suggests that nitrate tolerance is caused by increased levels of superoxide at the vascular wall, which leads to reduced nitric oxide level and to increased sensitivity to vasoconstrictive mechanisms, such as endothelin and angiotensin II. Intermittent dosing of nitrates allowing a 12-hour nitrate-free interval is effective in preventing nitrate tolerance and is, therefore, recommended. Recent information suggests that augmentation of nitrate dose by the use of an escalating dose regimen and a concomitant use of hydralazine can prevent or overcome the effect of nitrate tolerance in patients with heart failure.
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PMID:Nitrates in the treatment of congestive heart failure. 863 26

Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril (5 mg twice daily) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured minimal forearm vascular resistance (ratio of mean arterial pressure and forearm blood flow after heating, ischemia, and ischemic exercise) as an indirect estimate of vascular structure. Cilazapril decreased blood pressure (151 +/- 14/99 +/- 7 mm Hg during placebo to 138 +/- 17/89 +/- 8 mm Hg after cilazapril treatment, P<.01) and baseline (42.2 +/- 12.6 to 37.1 +/- 10.6 U, P<.05) and minimal (3.0 +/- 1.1 to 2.4 +/- 0.7 U, 15.9 +/- 20.2%; P<.05) forearm vascular resistances. The change in minimal forearm vascular resistance was unrelated to age, duration of hypertension, or changes in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6 +/- 1.0 to 11.4 +/- 5.9 mL/min per 100 mL and acetylcholine to 21.5 +/- 17.8. Both responses did not change after cilazapril. The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Therapy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.
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PMID:Effects of cilazapril on vascular structure and function in essential hypertension. 869 40

To assess the role of angiotensin II (AII) in the development of myocardial dysfunction during ischemia and reperfusion, the effects of either oral pretreatment with 1 mg/kg losartan or treatment with 4.5 mu M losartan in vitro were compared with effects measured in the respective placebo or in vitro control groups in an isolated rat working-heart model. Both groups treated with losartan showed significant improvement (p < 0.005) in functional recovery following 20 min of ischemia compared with the respective control groups. Coronary flow (CF) and cardiac output (CO) were also significantly increased during reperfusion in the drug treatment groups compared with controls (p < 0.05 to p < 0.001). The recovery of mechanical function, CO, and CF was significantly more rapid in hearts from rats treated orally with losartan than in hearts treated with losartan in vitro. As measured by 31P-nuclear magnetic resonance, the changes observed in ATP levels and in intracellular pH during ischemia and reperfusion were essentially the same under either treatment regimen. This article describes the initial observation of a significant reduction in myocardial dysfunction during reperfusion following 20 min of global ischemia in the isolated perfused heart as a result of acute AII AT1 receptor antagonism by losartan administered either directly in vitro or by oral pretreatment.
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PMID:Use of losartan to examine the role of the cardiac renin-angiotensin system in myocardial dysfunction during ischemia and reperfusion. 872 Apr 14

There are multiple causes of liver graft nonfunction in the early post-transplant period. Since a severe microcirculatory disturbance based on ischemia-reperfusion liver injury is considered to be the main underlying pathophysiology, it is suspected that various vasoactive substances are liberated after reperfusion of the graft. In order to investigate this matter, we conducted an experimental study with pig liver allotransplantation. Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/ kg body weight intravenously, given at the time of liver harvesting. All of the recipient animals in the treatment group (n = 10) survived longer than 7 days whereas three of ten animals in the control group died within 7 days. Serum lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was significantly lower in the treatment group (915.1 +/- 167.3 U/l) than in the control group (1264.4 +/- 134.7 U/l). Serum thromboxane B2 (2261.7 +/- 1055.7 pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment group were significantly lower than those in the control group (4220.0 +/- 1711.0 pg/ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin II after reperfusion tended to be lower in the treatment group than in the controls serum renin activity was less than 3 ng/ml in both groups of animals. There were no differences in the plasma endotoxin levels between the two groups. We conclude that the administration of sodium ozagrel to the donor animals provided better graft function in recipients than no such treatment. We speculate that the inhibition of thromboxane A2 production suppresses the liberation of other vasoconstrictive substances, preventing microcirculatory disturbance and, thereby, contributing to improved graft function after liver transplantation.
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PMID:Liberation of vasoactive substances and its prevention with thromboxane A2 synthase inhibitor in pig liver transplantation. 874 15


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