UMLS:C0022116 - FACTA Search

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

The effect of selective alpha 1-adrenoceptor blockade on regional myocardial blood flow and contractile function during exercise-induced myocardial ischemia was determined in nine dogs having chronic single vessel coronary stenosis (ameroid constrictor). Treadmill exercise performed after beta-adrenoceptor blockade (1.0 mg/kg i.v. propranolol), to block potential prejunctional effects recently recognized with alpha-blockade, elicited severe regional myocardial ischemia with a steady-state reduction of regional systolic wall thickening of the post-stenotic myocardium from a resting value of 21.8% to 7.0%. Blood flow to the ischemic subendocardium was reduced from 0.76 to 0.36 ml/min/g (microspheres). Prazosin (80 micrograms/kg i.v.) was administered during continued running, and angiotensin II was simultaneously infused to prevent the decrease in systemic arterial pressure caused by prazosin. During the subsequent steady state, with arterial pressure matched to the pre-prazosin level, regional subendocardial blood flow improved to 0.60 ml/min/g and systolic wall thickening in the post-stenotic region increased modestly to 10.2%. No changes in blood flow to the outer portion of the post-stenotic region or to the remote control region were seen, and prazosin caused no effect on regional function in the control area, indicating effective blockade of prejunctional effects of prazosin (demonstrated in pilot studies). The finding that blockade of alpha 1-adrenoceptors resulted in improved ischemic zone subendocardial blood flow and contractile function are consistent with alpha 1-adrenoceptor-mediated reduction of blood flow to the ischemic subendocardium during exercise-induced ischemia in dogs with beta-blockade.
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PMID:Alpha 1-adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs. 810 79

In a rat model, the left kidney was subjected to 60 min of normothermic ischemia followed by 15 min of reperfusion, whereas the right kidney, serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n = 12) or University of Wisconsin (UW) solution (n = 6) for 10 min. Each kidney was then harvested and stored at 4 degrees C in its respective solution. After 24 and 48 h of cold storage, the following vasoactive substances were measured in the preservation media: endothelin (ET), angiotensin II (A-II), thromboxane (B2) (TxB2), and prostaglandin I2 (PGI2). After 24 h in EC solution, left kidneys uniformly produced significantly higher concentrations of each vasoactive substance than right kidneys: ET 1.64 +/- 0.3 pg/ml vs 0.82 +/- 0.1 pg/ml (P < or = 0.009); A-II 20.8 +/- 6.2 pg/ml vs 7.75 + 2.3 pg/ml (P < or = 0.007); TxB2 100.8 +/- 17.7 pg/ml vs 40.1 +/- 11.7 pg/ml (P < or = 0.04); PGI2 638.3 +/- 41.1 pg/ml vs 318.3 +/- 36.4 pg/ml (P < or = 0.001), respectively. At 48 h, a similar pattern of results was obtained as the kidney continued to produce TxB2 and prostacyclins during the 24-48 h period. In the UW solution, basal levels of ET and A-II were lower than those in EC solution, but similarly increased after initial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measurement of the vasoconstrictive substances endothelin, angiotensin II, and thromboxane B2 in cold storage solution can reveal previous renal ischemic insults. 811 96

This review summarizes emerging evidence that supports the notion of a separate brain renin-angiotensin system (RAS) complete with the necessary precursors and enzymes for the formation and degradation of biologically active forms of angiotensins, and several binding subtypes that may mediate their diverse functions. Of these subtypes the most is known about the AT1 site which preferentially binds angiotensin II (AII) and angiotensin III (AIII). The AT1 site appears to mediate the classic angiotensin responses concerned with body water balance and the maintenance of blood pressure. Less is known about the AT2 site which also binds AII and AIII and may play a role in vascular growth. Recently, an AT3 site was discovered in cultured neoblastoma cells, and an AT4 site which preferentially binds AII(3-8), a fragment of AII now referred to as angiotensin IV (AIV). The AT4 site has been implicated in memory acquisition and retrieval, and the regulation of blood flow. In addition to the more well-studied functions of the brain RAS, we review additional less well investigated responses including regulation of cellular function, the modulation of sensory and motor systems, long term potentiation, and stress related mechanisms. Although the receptor subtypes responsible for mediating these physiologies and behaviors have not been definitively identified research efforts are ongoing. We also suggest potential contributions by the RAS to clinically relevant syndromes such as dysfunctions in the regulation of blood flow and ischemia, changes in cognitive affect and memory in clinical depressed and Alzheimer's patients, and angiotensin's contribution to alcohol consumption.
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PMID:Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. 817 Jun 22

Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.
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PMID:Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition. 820 52

The aim of the present study was to examine effects of changes in afterload on regional myocardial motion in acute ischemia. Ischemic and non-ischemic segment lengths of the left ventricular free wall were measured by miniature ultrasonic gauges in eleven open chest dogs with the pericardium preserved. In a stable state after left anterior descending coronary artery occlusion, peak left ventricular pressure was varied by the infusion of angiotensin II (n = 8) and sodium nitroprusside (n = 8). To exclude effects of preload on the responses, end-diastolic lengths of the non-ischemic region before and during infusion of each drug were matched with vena caval occlusion. When peak left ventricular pressure elevated from 113 +/- 2 (mean +/- S.E.)mmHg to 145 +/- 6, in isovolumetric contraction phase, degree of active shortening in the non-ischemic region and that of paradoxical expansion of the ischemic region did not change. In ejection phase, active shortening of the non-ischemic region decreased from 1.38 +/- 0.11 mm to 1.06 +/- 0.10 but that of the ischemic region remained unchanged. Stroke volume decreased from 14.5 +/- 1.3 ml to 10.8 +/- 1.0. When peak left ventricular pressure decreased from 111 +/- 4 mmHg to 101 +/- 6, in isovolumetric contraction phase, active shortening of the non-ischemic region decreased from 0.90 +/- 0.13 mm to 0.76 +/- 0.15 and paradoxical expansion of the ischemic region reduced from -0.95 +/- 0.11 mm to -0.80 +/- 0.11. In ejection phase, shortening of the non-ischemic region increased from 1.05 +/- 0.13 mm to 1.31 +/- 0.15 but that of the ischemic region did not change. Stroke volume increased from 11.5 +/- 1.3 ml to 14.0 +/- 1.4. These results indicate that in acute ischemia, changes in isovolumetric shortening of the non-ischemic region and paradoxical expansion of ischemic region are related with each other in isovolumetric contraction phase when afterload is altered and suggest that stroke volume is affected by the shortening of ejection phase in the non-ischemic region.
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PMID:Effects of changes in afterload on regional wall motion in acute ischemic canine heart. 821 67

In the present experiments the effect of long-term peripheral ischemia on the capillary of two hind limb skeletal muscles was investigated in spontaneously hypertensive rats. Furthermore, the effect of antihypertensive therapy on changes in capillarity and on the previously observed hyperreactivity of the ischemic vascular bed to vasoconstrictors was investigated in perfused hind limbs of rats after long-term treatment with the angiotensin I converting enzyme inhibitors captopril (0.5 mg/kg.h) or zabiciprilate (0.025 mg/kg.h), the angiotensin II type 1 receptor antagonist losartan (0.625 mg/kg.h), or the calcium antagonist felodipine (0.042 or 0.42 mg/kg.h). Skeletal muscle ischemia in the left hind limb was induced by partial ligation of the left common iliac artery. Long-term (4 weeks) ischemia increased significantly the capillary-to-fiber ratio in the soleus muscle, composed predominantly of type I fibers in spontaneously hypertensive rats, of the ischemic hind limb, whereas capillarity in the contralateral muscle was not affected. Furthermore, capillarity in the gastrocnemius muscle (type II muscle fiber part) of both the ischemic and contralateral hind limb did not change. Long-term treatment with the angiotensin I converting enzyme inhibitors during ischemia abolished the increase in the capillary-to-fiber ratio in the soleus muscle, whereas a comparable antihypertensive dose of felodipine had no effect. Greater blood pressure reductions by both losartan and felodipine prevented increases in capillarization in skeletal muscle ischemia. With respect to vascular hyperreactivity during ischemia, only treatment with losartan normalized reactivity of the ischemic vascular bed to vasoconstrictors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive therapy and adaptive mechanisms in peripheral ischemia. 822 38

The level of plasma endothelin (ET) was studied in 40 cases with acute myocardial infarction (AMI) with radioimmunoassay. The results showed that plasma ET level reached its peak value (46.01 +/- 1.64 pg/ml) immediately after AMI attack and dropped down (39.37 +/- 0.47 pg/ml) on the first day; The value was still high (15.56 +/- 1.40 pg/ml) on the twenty-eight day: this was significant higher than that in control group (6.35 +/- 0.44 pg/ml, P < 0.001). It was found that height of plasma ET level was closely correlated with severity of myocardial damage and degree of cardiac insufficiency. In order to evaluate the pathogenic role of ET in AMI, the effect of ET-antiserum on myocardial infarction (MI) was investigated on infarct model produced by ligature of left anterior descending coronary artery in rats. The results showed that plasma ET levels elevated significantly in rats with MI (8.4 +/- 1.0, sham 3.1 +/- 0.2 pg/ml, P < 0.01) and ET-antiserum administration dramatically decreased plasma ET level 65% (P < 0.01), lowered plasma content of lipid peroxide 27% (P < 0.01) and reduced infarct size 48% (P < 0.01). It is suggested that ET is an important factor which contributes to the pathogenesis of MI. Limb ischemia and reperfusion study was carried out in rats also. Metallothionein (MT) was found to antagonize markedly ET-induced vasoconstriction and lower the release of ET stimulated by angiotensin II in a dose-dependent manner. It is suggested that under certain pathological conditions MT may exert its injury--resistant and cell protective action.
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PMID:[A clinical and basic study on the relationship between acute myocardial infarction and endothelin]. 826 70

Coronary artery occlusion results in the acute activation of the renin-angiotensin system and production of angiotensin II, a potent vasoconstrictor and positive inotropic agent. This has raised the possibility that angiotensin converting enzyme (ACE) inhibitors might be "cardioprotective" (that is, might attenuate myocardial injury, dysfunction and necrosis) in the setting of acute ischemia and infarction. Captopril, enalapril and ramipril have, in fact, been reported to acutely limit myocardial injury and necrosis in models of permanent coronary artery occlusion. The mechanisms responsible for this cardioprotection are complex, but include favorable alterations in myocardial oxygen supply/demand, and, in some instances, inhibition of bradykinin metabolism and/or increased prostaglandin synthesis. Other studies, however, have failed to document a reduction in infarct size with ACE inhibitor treatment. Results obtained in models of coronary occlusion/reperfusion have also been mixed. In models of brief transient ischemia not associated with necrosis, captopril and zofenopril have consistently been found to attenuate postischemic contractile dysfunction of the viable but "stunned" myocardium during the early hours following relief of ischemia. In contrast, there is no consensus on the effects of enalapril on the stunned myocardium: both positive and negative results have been obtained. Similar disparity has been reported in models of more prolonged ischemia/reperfusion resulting in subendocardial necrosis: some studies have reported myocardial salvage, while others have provided disturbing evidence of apparent exacerbation of myocardial necrosis with captopril and enalapril therapy. Thus, after a decade of investigative effort, the question of whether ACE inhibitors are "cardioprotective" in the setting of acute myocardial ischemia and infarction remains unresolved. Nonetheless, clinical protocols are in progress to assess the effects of early ACE inhibitor treatment in patients with acute myocardial infarction.
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PMID:"Cardioprotection" by ACE-inhibitors in acute myocardial ischemia and infarction? 835 29

There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II, ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearrangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in the case of non-thiol-containing molecules). What is clear is that the enhanced recovery of function effected by these drugs is not due to hemodynamic effects, inhibition of the converting enzyme per se, or an "antischemic" action (since the drugs were effective when given at the time of reperfusion). The effects of ACE inhibitors on myocardial infarct size remain controversial. Further studies will be necessary to conclusively establish whether ACE inhibitors can protect against the detrimental effects of myocardial ischemia and reperfusion. Nevertheless, the evidence provided thus far is encouraging and warrants an in-depth assessment of the role of these drugs in attenuating myocardial ischemia/reperfusion injury.
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PMID:Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview. 835 31

The kidney responds to periods of ischemia with vasoconstriction and a decrease in glomerular filtration rate (GFR) on reperfusion. The mediators of this response have not been fully identified. In this study, we examined the contribution of angiotensin II (AII), thromboxane A2 (TXA2) and the interaction between them to this response. Anesthetized dogs were subjected to 30 min of clamping of both renal arteries. Renal hemodynamics and function were followed from 60 min before and for 105 min after clamping. Dogs were divided into salt-depleted (AII-stimulated) and captopril-treated (AII-inhibited) groups. Each group included dogs that received either the TXA2 synthase inhibitor CGS 13080 or its vehicle (controls) starting 30 min before renal artery clamping and lasting to the end of the experiment. In captopril-treated control dogs, 30 min of ischemia induced a 25% fall in renal blood flow (RBF). GFR initially fell by 75%, but recovered to 64% of base-line value 60 to 90 min after release of the clamp. In captopril-treated dogs, CGS 13080 prevented the fall in RBF, but the GFR response was similar to vehicle-treated dogs. In control dogs, both GFR and RBF responses were enhanced in salt-depleted compared with captopril-treated dogs; the decrease in RBF (44%) was greater, and the recovery in GFR, which fell by 89%, less. In salt-depleted, CGS 13080-treated dogs, the 30% fall in RBF was less than its control, but greater than dogs treated with captopril and CGS 13080. The change in GFR was similar to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction between thromboxane A2 and angiotensin II in postischemic renal vasoconstriction in dogs. 845 Apr 63

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