Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/beta-adrenoceptor pathway.
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PMID:Administration of angiotensin II in the paraventricular nucleus protects gastric mucosa from ischemia-reperfusion injury. 1844 92

As angiotensin II may underlie the deleterious effects of some vascular diseases, we have examined the role of this peptide on the cerbrovascular endothelin-1 action after ischemia-reperfusion. In anesthetized goats, 1 hour-occlusion followed by 1 hour-reperfusion of the left middle cerebral artery (MCA) was induced, and then segments 3-mm in length from branches of the right MCA (control) and the left MCA (ischemic) were obtained for isometric tension recording. Endothelin-1 (10(-11)-10(-7) M) produced a contraction that was higher in ischemic than in control arteries, and in control but not in ischemic arteries this contraction was potentiated by angiotensin II (10(-7) M). Losartan (3 x 10(-6) M), antagonist of AT1 receptors, did not affect the response to endothelin-1 in control arteries, but reduced it both in ischemic arteries and angiotensin II-treated control arteries. PD123,319 (3 x 10(-6) M), antagonist of AT2 receptors, or the inhibitor of nitric oxide synthesis L-NAME (10(-4) M) did not alter the arterial effects of endothelin-1. Therefore, angiotensin II may potentiate the constriction to endothelin-1 in normal cerebral arteries by activating AT1 receptors. The observed cerebrovascular increased response to endothelin-1 after ischemia-reperfusion might be related in part to activation of AT1 receptors under this condition.
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PMID:Role of angiotensin II in the response to endothelin-1 of goat cerebral arteries after ischemia-reperfusion. 1913 74

Random pattern skin flaps are still widely used in plastic surgery. However, necrosis in the distal portion resulting from ischemia is a serious problem, increasing the cost of treatment and hospitalization. To enhance skin flap viability, a variety of pharmacologic agents have been intensively investigated. The aim of this study was to assess the effect of enalapril (an angiotensin-converting enzyme inhibitor) and losartan (an angiotensin receptor blocker) in skin flap viability. Male rats of 200 to 250 g were used. Different doses of enalapril (5, 20, and 50 mg/kg) and losartan (5 mg/kg) were administrated 30 minutes prior to elevate the flap. Flap survival area was evaluated on the seventh postoperative day. Enalapril improved survival area in a dose-dependent manner, but losartan failed to improve survival area, which suggested that the effect of enalapril was not mediated through AT1 receptors.
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PMID:The effect of enalapril on skin flap viability is independent of angiotensin II AT1 receptors. 1946 Dec 89

Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and endothelin -1 (ET-1) are suggested to be important links between placental ischemia and hypertension during preeclampsia. Activation of the angiotensin II type 1 receptor (AT1R) increases endothelial cell production of ET-1; however, the importance of ET-1 in response to AT1-AA-mediated AT1 R activation during preeclampsia is unknown. Furthermore, the role of AT1-AA-mediated increases in blood pressure during pregnancy remains unclear. The objective of this study was to test the hypothesis that AT1-AA, increased to levels observed in preeclamptic women and placental ischemic rats, increases mean arterial pressure (MAP) by activation of the ET-1 system. Chronic infusion of purified rat AT1-AA into normal pregnant (NP) rats for 7 days increased AT1-AA from 0.68+/-0.5 to 10.88+/-1.1 chronotropic units (P<0.001). The increased AT1-AA increased MAP from 99+/-1 to 119+/-2 mm Hg (P<0.001). The hypertension was associated with significant increases in renal cortices (11-fold) and placental (4-fold) ET-1. To determine whether ET-1 mediates AT1-AA-induced hypertension, pregnant rats infused with AT1-AA and NP rats were treated with an ET(A) receptor antagonist. MAP was 100+/-1 mm Hg in AT1-AA+ET(A) antagonist-treated rats versus 98+/-2 mm Hg in ET(A) antagonist-treated rats. Collectively, these data support the hypothesis that one potential pathway whereby AT1-AAs increase blood pressure during pregnancy is by an ET-1-dependent mechanism.
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PMID:Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: role of endothelin-1. 1970 4

First, an update of the vascular systemic and tissue renin-angiotensin-aldosterone system is provided to explain how it is regulated at the systemic and tissue levels, and how many angiotensin peptides and receptors can be modulated by the various antihypertensive drugs. Second, experimental data is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers and angiotensin-converting enzyme inhibitors, because they increase activation of angiotensin AT2 and AT4 receptors. Indeed, these trigger brain anti-ischemic mechanisms by favouring cerebral blood flow (angiogenesis and recruitment of pre-existing collateral circulation, specifically in the ischemic brain where AT2 receptors are overexpressed) or by directly increasing neuronal resistance to anoxia. Third, we review most of the large primary and secondary stroke prevention trials as well as the ACCESS acute stroke trial in which antihypertensive drugs were evaluated. With the exception of the secondary stroke prevention trial PRoFESS, most trials support the hypothesis that angiotensin II-increasing drugs confer specific blood pressure-independent brain ischemia protection when compared with angiotensin II-decreasing drugs or placebo. A careful analysis of the PRoFESS trial, however, reveals study design limitations, the main one being that diastolic BP (<80 mmHg) in the first month post-stroke may have been too low in at least one third of the population with baseline systolic blood pressure less than 130 mmHg, because a high dose of telmisartan was given after a very short post-stroke delay (median 15 days) without discontinuation of the baseline antihypertensive treatment.
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PMID:Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors? 1976 45

Autophagic activity increases in the heart in response to a variety of stresses including hypertension, ischemia and neonatal starvation. Constitutive autophagy plays an important role in the maintenance of cellular homeostasis in the heart, whereas unrestrained autophagic activity accentuates the maladaptive cardiac remodeling response to stress (e.g., hypertension) and may contribute to the pathogenesis of heart failure. A detailed understanding of the molecular mechanisms governing autophagy induction and autophagosome maturation is evolving, but little is currently known about the extra- and intracellular cues that trigger autophagic induction in the heart. The renin-angiotensin system (RAS) is implicated in the pathogenesis of a number of cardiovascular conditions including hypertension, cardiac hypertrophy, myocardial infarction and heart failure. We now provide the first link between angiotensin II (AngII) and autophagy regulation in the heart. We demonstrate that AngII increases autophagosome formation via the AngII type I (AT1) receptor and that this response is constitutively antagonized by co-expression of the AngII type 2 (AT2) receptor in neonatal cardiomyocytes.
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PMID:Cardiomyocyte autophagy is regulated by angiotensin II type 1 and type 2 receptors. 1995 53

PURPOSE. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. METHODS. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bradykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Immunohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinography (ERG) was also performed. RESULTS. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immunohistochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. CONCLUSIONS. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the subsequent ischemic damage in the rat retina.
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PMID:Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin II type 1 receptor. 2016 47

Reactive oxygen species are known to be derived from NADPH oxidase in several tissues. Angiotensin II was suggested to be involved in the activation of NADPH oxidase; however, its role in the gastric mucosa is unclear. We examined the roles of angiotensin II receptor and NADPH oxidase in ischemia/reperfusion-induced gastric damage in rats. Under urethane anesthesia, male Sprague-Dawley rat stomachs were mounted in an ex-vivo chamber, had 100 mM HCl applied to them, and then a catheter was passed through the femoral vein. Ischemia/reperfusion was accompanied by blood collection and reperfusion through the catheter. Losartan, candesartan, valsartan, which are AT1 receptor blockers (ARB); PD123319, an AT2 receptor blocker; enalapril, an ACE inhibitor; or diphenylene iodonium, a NADPH oxidase inhibitor, was given i.v. 10 mins, and beta-NADPH, a NADPH oxidase substrate, was given i.v. 5 mins before reperfusion. The gastric damage by ischemia/reperfusion was attenuated by treatment with any of ARB or enalapril, but was not affected by PD123319. The increase in gastric H(2)O(2) production and microvascular permeability by ischemia/reperfusion was also suppressed by treatment with any of ARB or enalapril. In rat gastric mucosa, the NADPH oxidase subunit p47(phox) was detected. Additionally, diphenylene iodonium had similar effects to ARB against ischemia/reperfusion-caused gastric damage, increased H(2)O(2) production, and microvascular permeability. Ischemia/reperfusion activated NADPH oxidase in the gastric mucosa, and the activation was significantly attenuated by treatment with losartan or diphenylene iodonium. These results suggest that ischemia/reperfusion generated reactive oxygen species are derived from NADPH oxidase activation via AT1 receptor in rat stomachs.
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PMID:Evidence for the involvement of NADPH oxidase in ischemia/reperfusion-induced gastric damage via angiotensin II. 2043 17

The impact of some types of antihypertensives on carbohydrate metabolism and their association with type 2 diabetes is well-known. In this respect, ACE inhibitors, AT1 blockers or I1 imidazoline agonists, known to improve insulin sensitivity, are the first line therapeutic choice. Metabolism-neutral calcium channel blockers, particularly the dihydropyridines, are the second in line of therapeutic options. On the other hand, beta-blockers and diuretics, thiazide in particular, exert negative effect on carbohydrate metabolism. Should their use be still desirable, e.g. due to co-morbidities, it is advisable to select cardio-selective beta-blockers or beta-blockers with ISA activity, since the effect of these agents on carbohydrate and lipid metabolism is less significant. Diuretics should then be used only in combination therapy and in small doses; potassium-sparing or metabolically neutral indapamide derivatives should be selected. The benefit of cardioprotectivity, gained from the treatment with cardioselective beta-blockers will, particularly in patients with ischemic heart disease, usually outweigh the risk of metabolic adverse effects. Combination therapy, using AT1 blockers or ACE inhibitors in combination with calcium channel blockers or diuretics, should be utilized to its full potential in order to ensure that target values are achieved. Recently completed studies provide the evidence to support this approach. Hypertension in patients with lower limb ischemia increases the already high cardiovascular risk in these patients. Blood pressure reduction as such is more important than a specific antihypertensive.
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PMID:[Treatment of hypertension in patients with diabetes mellitus and lower limb ischemia]. 2046 1

Matrix metalloproteinase-9 (MMP-9) which is a member of matrix metalloproteinases family that normally remodel the extracellular matrix, has been shown to play an important role in both animal models of cerebral ischemia and human stroke. The expression of MMP-9 is elevated after cerebral ischemia which is involved in accelerating matrix degradation, disrupting the blood-brain barrier, increasing the infarct size and relating to hemorrhagic transformation. Recently, many drugs, such as tetracycline derivatives, cyclooxygenase inhibitors, ACEI inhibitors and AT1 receptor blockers, etc., have been found to attenuate the elevated expression levels of MMP-9 after ischemia and to reduce the damage of cerebral ischemic. This article reviews the physiological features of MMP-9 and its important role in the genesis, propagation, and therapeutics of cerebral ischemic diseases.
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PMID:Mmp-9, a potential target for cerebral ischemic treatment. 2051 6


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