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)

In patients with pump failure complicating acute infarction, vasodilating drugs, by reducing impedance to left ventricular outflow and venous return to the heart, improve cardiac performance without affecting myocardial contractility. Sodium nitroprusside currently is the vasodilator of choice in most patients with both elevated left ventricular filling pressures and reduced cardiac output. Patients with accompanying mechanical defects, such as acute mitral regurgitation or ventricular septal rupture, are particularly amenable to vasodilator therapy. Some patients may require combined therapy, with inotropic catecholamines or mechanical assistance devices together with vasodilators, in order to avoid undesirable hypotension. Side effects and toxicity are rare when patients are carefully selected and monitored. It is uncertain whether vasodilators reduce ischemia or salvage jeopardized myocardium, but they appear to improve the initial prognosis of some patients with severe pump failure. The long-term prognosis of these patients remains poor, however, and therefore a more aggressive approach to their chronic management seems warranted.
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PMID:Vasodilator therapy of pump failure complicating acute myocardial infarction. 10 78

The Po2 was measured in the tissue of the ileal wall of dogs before, during, and up to one hour after reversible occlusion of segmental arteries. The occlusion was then released and the reoxygenation of the bowel wall was observed. Sodium nitroprusside (50 mg in 100 ml of solution) applied topically to the ischemic segment enhanced reoxygenation as compared to control animals. Nitroprusside absorbed into the portal system did not cause hypotension, as is usual with systemic administration, because nitroprusside is inactivated by passage through the liver. Topically applied sodium nitroprusside alleviates intestinal ischemia by direct local vasodilatation and relaxation of smooth muscle spasm in the ischemic bowel wall. The intraperitoneal use of sodium nitroprusside should be clinically evaluated in situations where visceral perfusion is impaired.
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PMID:Enhancement of tissue Po2 of strangulated bowel by topical application of sodium nitroprusside. 68 8

Hemodynamic measurements were performed and ECG recorded before and shortly after infrarenal aortic cross-clamping during operation for abdominal aortic aneurysm in five patients without evidence of heart disease (group I) and in ten patients with severe coronary artery disease (group II). All patients sustained an increase in systemic arterial pressure. Group I demonstrated a decrease in pulmonary artery, pulmonary capillary wedge (PCW), and central venous pressures when the aorta was clamped, whereas group II demonstrated an increase. The difference in response of the groups is significant (P less than 0.05). All three patients who responded to cross-clamping with increases of 7 mm Hg or greater in PCW demonstrated myocardial ischemia during cross-clamping. None of the values measured prior to cross-clamping predicted with certainty the response to cross-clamping. Sodium nitroprusside reversed the elevation of left ventricular filling pressure in all three patients, and in two patients, relieved evidence of myocardial ischemia concurrently. In the third patient, ventricular irritability was abolished by lidocaine and did not recur. We conclude that infrarenal aortic cross-clamping may cause myocardial ischemia in patients with severe coronary artery disease. This ischemia may be predicted by a rise in PCW at the time of cross-clamping, and vasodilator therapy is indicated in such patients.
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PMID:Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease. 126 32

The activity of soluble guanylate cyclase (GC) and its regulation in the platelets and heart of normal rats and rats with experimental acute myocardial ischemia provoked by coronary ligation was examined. There was a synchronous reduction in platelet and heart GC activity immediately following 15 minutes after surgery along with a drastically marked drop in genuine baseline activity (with Mg2+) to 19 and 40% in the platelets and heart (both ischemic and intact areas), respectively. Following 24 hours, GC activity insignificantly rose (up to 35.5%) in the platelets with Mg2+, that with Mn2+ remained unchanged; in the ischemic area it decreased much more (to 30%), whereas in the intact area it partially restored (up to 70%). The stimulating effect of DTT on platelet GC activity 15 minutes after the surgery drastically rose (from 2.8 to 8), then returning to normal 24 hours later. The findings show an enhancement in free radical processes typical of ischemia and indicate their high response of platelet GC at the earliest stages. Sodium nitroprusside-induced activation of myocardial GC diminished in the ischemic area in 15 minutes and virtually lacked in 24 hours. There was a less pronounced decrease in GC activation in the intact area. It is suggested that lower enzymatic activatibility is associated with heme loss. The absence of sodium nitroprusside-induced stimulation of platelet GC both in health and in the abnormality under question may be due to primary heme enzymatic deficiency.
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PMID:[Soluble guanyl cyclase of blood platelets and heart of rats with experimental myocardial ischemia]. 135 20

Attenuated cholinergic vasodilatation has been suggested as an endothelium-related mechanism involved in essential hypertension. We investigated the role of muscarinic (M) receptor subtypes in the forearm resistance vasculature. In eight white men with essential hypertension and eight matched normotensive control subjects (age of both groups, 47 +/- 4 years; mean +/- SEM), we infused the nonselective agonist methacholine in the presence of saline and the antagonists atropine (nonselective), pirenzepine (M1-selective), and AF-DX 116 (M2-selective) into the brachial artery and measured forearm blood flow and forearm vascular resistance using venous occlusion plethysmography. Affinity constants (pKb values) were determined from calculated plasma concentrations of the infused compounds and EC50 values. Sodium nitroprusside was given as an endothelium-independent control, and minimal forearm vascular resistance after 10 minutes of ischemia was used as a marker of structural vascular changes. Hypertensive patients showed higher minimal forearm vascular resistance, indicating structural vascular changes. However, sodium nitro-prusside- and methacholine-induced vasodilatation was similar in both groups, with apparent EC50 values (log moles per liter; mean +/- SEM) of -7.32 +/- 0.13 and -7.51 +/- 0.21 in hypertensive patients and -7.37 +/- 0.13 and -7.45 +/- 0.02 in control subjects, respectively. Atropine, pirenzepine, and AF-DX 116 caused a shift to the right of the concentration-response curve of methacholine, with apparent pKb values of 8.63 +/- 0.08, 6.81 +/- 0.13, and 5.51 +/- 0.29 in hypertensive individuals and 8.62 +/- 0.10, 6.98 +/- 0.08, and 5.49 +/- 0.09 in control subjects, respectively. Again, there were no statistically significant differences in these pharmacological parameters between hypertensive patients and normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo characterization of muscarinic receptor subtypes that mediate vasodilatation in patients with essential hypertension. 760 35

Aortic occlusion and revascularization (I-R) may lead to lung injury dependent on activated neutrophil adherence. Nitric oxide (NO) inhibits neutrophil adherence to endothelial cells. We studied the effect of increasing or decreasing NO levels with sodium nitroprusside (SNP) or N-nitro-L-arginine methyl ester (L-NAME) in an I-R lung injury model of 30 min ischemia followed by 120 min reperfusion. Sprague-Dawley rats (10/group) were randomized to controls, I-R, I-R treated with L-NAME (10 mg/ml/hr), and I-R treated with SNP (0.2 mg/ml/hr). Myeloperoxidase activity (MPO) was used as a measure of pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio and bronchoalveolar lavage protein (BAL prot) and neutrophil counts (BAL PMN). Aortic occlusion and revascularization led to significant increases in pulmonary neutrophil influx (6.1 +/- 0.1 MPO u/g vs 3.05 +/- 0.4 MPO u/g in the control group, P < 0.001) and microvascular leakage; BAL prot (347 +/- 32 mg/ml in controls vs 454 +/- 16 mg/ml in the I-R group, P < 0.05); and BAL PMN (0.7 +/- 0.05 in controls vs 1.8 +/- 0.07 PMN/ml in the I-R group, P < 0.001). These changes were exacerbated further by administration of L-NAME (MPO = 8.9 +/- 0.7; BAL prot = 581 +/- 40 mg/ml; BAL PMN = 2.7 +/- 0.16 PMN/ml). Sodium nitroprusside therapy attenuated the I-R-induced lung injury (3.5 +/- 0.4 MPO u/g, P < 0.05 vs I-R; BAL prot = 330 +/- 61 mg/ml; BAL PMN = 0.9 +/- 0.1 PMN/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide (endothelium-derived relaxing factor) attenuates revascularization-induced lung injury. 804 Nov 46

Nitric oxide appears to play an important role in maintaining gastric mucosal integrity. This study aimed to investigate whether a nitric oxide donor (sodium nitroprusside) or stimulation of endogenous nitric oxide synthesis (with acetylcholine) protects against gastric ischemia-reperfusion injury. Rats were subjected to 30 min of ischemia followed by 15 min of reperfusion. Injury was assessed by quantitative histology. Intravenous sodium nitroprusside (50-75 micrograms/kg) or acetylcholine (10-25 micrograms/kg), immediately before reperfusion, significantly reduced the percentage of mucosal injury compared with controls. Inhibition of nitric oxide synthesis by topical application of 12.5 mg/kg NG-methyl-L-arginine before acetylcholine treatment, abolished the effects of acetylcholine. The protective effects of acetylcholine and sodium nitroprusside did not appear to be related to local vasodilation since neither drug improved gastric blood flow and infusion of a non-nitric oxide vasodilator (papaverine, 1 mg/kg), had no protective effect on reperfusion injury. Sodium nitroprusside (50 micrograms/kg) and acetylcholine (25 micrograms/kg) significantly reduced polymorphonuclear leukocyte infiltration and extravasation into the mucosa compared with controls. NG-Methyl-L-arginine pretreatment before acetylcholine abolished these effects. We conclude that nitric oxide generators significantly reduce mucosal injury following ischemia-reperfusion and that this may occur via a reduction in polymorphonuclear leukocyte infiltration into the mucosa.
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PMID:Protection against gastric ischemia-reperfusion injury by nitric oxide generators. 831 20

Ischemia produces functional and structural alterations in peripheral blood vessels. Our study was designed to investigate alpha-adrenoceptor modifications induced by prolonged ischemia and their role in enhancing the contractile response during reperfusion in canine femoral arteries. Unilateral vessel ischemia was created by double crossclamping a femoral artery and was maintained for 3 hr. Reperfusion was allowed for 1 hr. The contralateral femoral artery was utilized as a control. The vessels were harvested for contractile and binding studies. Isometric tension studies revealed that the magnitude of the maximum contractile response to norepinephrine (NE), potassium chloride (KCl), and methoxamine was 671 +/- 82 mg/mm2 versus 245 +/- 43 mg/mm2 (P < 0.01), 485 +/- 46 mg/mm2 versus 229 +/- 62 mg/mm2 (P < 0.05), and 486 +/- 88 mg/mm2 versus 126 +/- 38 mg/mm2 (P < 0.01), respectively for ischemic and nonischemic femoral arteries. EC50 values showed that ischemic vessels were more sensitive to NE, KCl, and methoxamine (P < 0.05). Sodium nitroprusside induced concentration-dependent and complete relaxation in all arterial rings (100% relaxation) but the ischemic femoral artery showed less sensitivity (P < 0.05). Binding studies showed that the number of binding sites (Bmax) for [3H]Prazosin and [3H]Rauwolscine were significantly increased in ischemic versus nonischemic vessels (1261 +/- 95 fmole/mg versus 704 +/- 113 fmole/mg, P < 0.03, and 490 +/- 86 fmole/mg versus 175 +/- 15 fmole/mg, P < 0.04, respectively). Furthermore, a significant decrease in affinity (Kd) for [3H]Prazosin and [3H]Rauwolscine was observed in ischemic versus nonischemic tissues (9.4 +/- 1.7 nM versus 4 +/- 0.2 nM, P < 0.02, and 6.4 +/- 1.5 nM versus 1.8 +/- 0.6 nM, P < 0.01, respectively). The increase in canine femoral artery vasoreactivity, following prolonged ischemia, seems to be also due to an increased density and functional activity of alpha-adrenoceptors expressed by the ischemic arterial smooth muscle cells.
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PMID:Ischemia-induced peripheral arterial vasospasm role of alpha 1- and alpha 2-adrenoceptors. 863 38

The assessment of endothelial function in hypertensive patients receiving acetylcholine has revealed conflicting results. Whether an impaired flow response to acetylcholine is explained solely by a diminished endothelial synthesis of nitric oxide (NO) remains unclear as yet. In the present study, we tested the hypothesis that mechanisms other than reduced NO synthesis contribute to the hypertension-associated impairment of endothelium-dependent vasodilation. Therefore, the dilatory response to endogenous and exogenous NO was measured in resistance arteries and cutaneous microvessels in the forearm circulation of 12 normotensive individuals and 17 hypertensive patients. In addition, the overall dilatory capacity was assessed by peak flow during reactive hyperemia after 3 minutes of ischemia. Forearm blood flow was quantified by venous occlusion plethysmography at rest, during application of the NO donor sodium nitroprusside, and during stimulation of endogenous NO synthesis by acetylcholine and bradykinin. Blood flow velocity in the cutaneous microvasculature was measured with laser-Doppler flowmetry in parallel. Resting forearm flow was comparable in both groups (3.1 +/- 0.2 and 3.4 +/- 0.2 mL.min-1.100mL-1 tissue), whereas blood pressure and thus peripheral vascular resistance was significantly elevated in hypertensive compared with normotensive subjects. Hyperemic peak flow was significantly blunted in hypertensive patients. Sodium nitroprusside, acetylcholine, and bradykinin increased flow in a dose-dependent manner to a comparable extent in the control group (13.3 +/- 0.8, 13.6 +/- 1.3, and 14.6 +/- 0.7 mL.min-1.100mL-1 tissue, respectively). In contrast, in hypertensive patients maximum increase in resting flow was significantly reduced (sodium nitroprusside, -36%; acetylcholine, -44%; and bradykinin, -56%). The flow response after stimulation of endogenous NO synthesis by bradykinin was significantly more blunted compared with that of exogenous NO after application of sodium nitroprusside. In the cutaneous microvasculature, bradykinin-induced increases in blood flow velocity were selectively impaired in hypertensive patients, whereas flow response to acetylcholine was preserved. Thus, we conclude that in arterial hypertension endothelium-dependent, NO-mediated dilation of resistance arteries and cutaneous microvessels of the forearm vasculature is heterogeneously impaired, depending on the type of endothelial receptor stimulated. Furthermore, the present data suggest that in hypertensive patients the impairment of NO-dependent dilation of resistance arteries is caused by at least three different mechanisms: (1) a reduced endothelial synthesis of NO due to either a disturbed signal-transduction pathway and/or a reduced activity of NO synthase, (2) an accelerated NO degradation within the vessel wall, and (3) alterations in the vessel architecture resulting in an overall reduced dilatory capacity of resistance arteries.
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PMID:Evidence for a multifactorial process involved in the impaired flow response to nitric oxide in hypertensive patients with endothelial dysfunction. 869 36

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


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