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

Following vascular occlusion, development of collateral circulation occurs in at least two time-related phases: (1) the fast enhancement of the function of preexisting channels and (2) the slow formation of new vessels. Inasmuch as the renin-angiotensin system can act as a protective mechanism against local ischemia by activating preexisting collateral vessels, it is of interest to establish whether angiotensin II also produces stimulation of new vessel formation. Angiotensin II or cholecystokinin, an unrelated peptide, was incorporated in a slow-release formulation polyacrylamide gel and implanted in a pocket made in the rabbit cornea. Periodic examinations revealed that angiotensin II significantly stimulates new vessel formation; maximum values were attained in approximately 2 to 3 weeks. In contrast, cholecystokinin or polyacrylamide gel alone failed to stimulate any significant new vessel formation. Positive neovascularization was present in 85% of the total number of corneas implanted with angiotensin II, whereas 14% and 8% positive results were seen in the corneas implanted with either cholecystokinin or polyacrylamide gel alone, respectively. It is concluded that angiotensin II not only facilitates the activation of preexisting collateral vascular pathways but also has angiogenic properties and therefore could play an active role not only in the fast but also in the slow phase of the development of collateral circulation.
 ...
PMID:Neovascularization produced by angiotensin II. 257 74

Nineteen mongrel dogs had 30 minutes of thoracic aortic occlusion to determine the effects that blockade of the renin-angiotensin system may have on preserving spinal cord blood flow and function during a period of temporary spinal cord ischemia. Cross-clamping of the thoracic aorta causes renal ischemia and activates the renin-angiotensin system with resulting increased production of angiotensin II. Angiotensin II is a potent peripheral constrictor and elevated levels may constrict collateral spinal cord circulation. At the time of aortic cross-clamping, 10 dogs received 100 mg/kg of MK422 (intravenous enalapril maleate), a converting enzyme inhibitor, and nine animals served as controls. The blockade of the renin-angiotensin system had no preserving effects on spinal cord flow as measured by microspheres and on spinal cord function as graded with the Tarlov scale. However, the paraplegic animals all had significantly increased lower thoracic and lumbar spinal cord flows 30 minutes after clamp release when compared with those animals that remained neurologically intact. In conclusion, marked hyperemia occurring after a period of hypoperfusion may lead to spinal cord edema and compartment syndrome with resulting paraplegia.
 ...
PMID:The effect of hyperemia on spinal cord function after temporary thoracic aortic occlusion. 317 89

Glomerular visceral epithelial cells (podocytes) undergo flattening and spreading of major processes detectable by scanning electron microscopy in early postischemic acute renal failure in both animals and man. The authors examined the kinetics of development of these epithelial cell changes in the renal pedicle-clamping model of ischemic renal failure in the rabbit. They found that these changes develop progressively, increasing with increasing length of ischemia, and occur while the pedicle clamp is still in place. To assess the possible role of angiotensin II and vasopressin in producing the epithelial changes, the authors compared glomerular morphology before and during pedicle clamping in hydrated rabbits and in dehydrated rabbits. Dehydration alone produced changes in glomerular epithelial cells comparable to those seen in the postischemic kidney. The angiotensin-converting enzyme inhibitor captopril did not prevent the podocyte changes in either group. In vitro incubation studies confirmed that both angiotensin II and vasopressin produce glomerular epithelial cell changes with a threshold between 10(-7) M and 10(-8) M, a concentration that may be physiologically significant for angiotensin II, which is synthesized at the glomerulus and may have local paracrine effects. Such local synthesis may not be inhibited by systemic administration of captopril. Angiotensin II may play a role in producing podocyte alterations during renal ischemia, as well as in the dehydrated state.
 ...
PMID:Glomerular epithelial cell changes after ischemia or dehydration. Possible role of angiotensin II. 669 12

Myocardial interstitium plays an important role in the regulation of cardiac function compared with myocytes and it is actively involved in ischemia-reperfusion damage and in the acute and chronic remodelling during ischemic heart diseases. Myocardial post-ischemic oedema seems to interfere in this process. Myocardial oedema is able to induce structural alterations, to reduce myocardial function and to activate the renin-angiotensin-aldosterone system. Angiotensin II and aldosterone seem to be the cause of myocardial fibrosis that is detected during ischemic heart disease. Post-ischemic vascular permeability alterations have a similar role. In clinical conditions, ACE-inhibitors have important effects on cardioreparation and are able to improve cardiac function and reduce early and late mortality. The effects of myocardial oedema reduction (i.e. hypertonic reperfusion) on ischemia-reperfusion damage and myocardial fibrosis are still to clarify. A reduction in myocardial fibrosis may improve cardioreparation and prevent congestive heart failure, following ischemic heart disease.
 ...
PMID:[Role of interstitial myocardium in ischemia-reperfusion injury: experimental data and clinical implications]. 763

Angiotensin II is well known to have a cardiotoxic effects. However, it is still unclear whether exogenous angiotensin I or angiotensin II has a deleterious effect on myocardial ischemia-reperfusion injury. To examine this deleterious effects, we administered angiotensin I and angiotensin II to perfused hearts before ischemia, and measured creatine kinase (CK) release and cardiac function during subsequent reperfusion. Wistar Kyoto rats were used and the hearts were perfused by the Langendorff technique at a constant flow (10 ml/min). Seven hearts were perfused for 20 min and then subjected to 15 min of global ischemia (Control). In the experimental groups, during the 5 min before ischemia, we administered 100 ng/ml angiotensin I (Ang I; n = 9), 1 microgram/ml enalaprilat (ACEI; n = 5), both agents (ACEI + Ang I) (n = 6), or 10 ng/ml angiotensin II (Ang II; n = 6). The perfusates were then sampled to measure angiotensin II. After 15 min of ischemia, the hearts were reperfused with control perfusate. Throughout the 20 min of reperfusion, the effluent was collected to measure cumulative CK release. Angiotensin I increased coronary perfusion pressure (CPP) by 32 +/- 4 mmHg, however, the angiotension converting enzyme inhibitor inhibited the increase of CPP by angiotension I (11 +/- 1 mmHg) (p < 0.01). The contents of angiotensin II in the effluent in Ang I and Ang I + ACEI were 11.5 +/- 1.9 ng/ml and 4.0 +/- 0.5 ng/ml (p < 0.01). After 20 min of reperfusion, the left ventricular developed pressure was unchanged in all of the groups. CPP was also unchanged by ischemia in all of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The deleterious effects of exogenous angiotensin I and angiotensin II on myocardial ischemia-reperfusion injury. 802 51

The role of cardiac endothelin-1 (ET-1) was studied by determining endogenous tissue and coronary ET-1 levels in isolated rat hearts. Hearts were perfused in an upside-down position with a colloid-free buffer and immunoreactive ET-1 was determined in timed collections of coronary effluent (E) and interstitial fluid (transudate, T) produced by the ventricles and appearing on their surface. Basal ET-1 concentrations were 0.2 +/- 0.01 pg/ml (T) and 0.03 +/- 0.002 pg/ml (E), i.e., the T:E concentration ratio was 7. Angiotensin II (0.1 mumol/L) or thrombin (5 U/ml) increased coronary perfusion pressure and ET-1 secretion but had no effect on the T:E ET-1 concentration ratio (5 and 9). In two different protocols of ischemia/reperfusion, T and E concentrations increased up to two- and fivefold, respectively. The T:E ratios were approximately 2, and the highest concentrations in either fluid were < 1 pg/ml. No change in coronary perfusion pressure was observed. In the presence of the ET-1-converting enzyme inhibitor phosphoramidon (1.7 mumol/L), ischemia-induced increases of ET-1 concentrations were attenuated in parallel with a time-dependent rise in coronary perfusion pressure. Therefore, under normoxic conditions and in ischemia/reperfusion, ET-1 is an endogenous vasodilator in the rat heart.
 ...
PMID:Cardiac tissue endothelin-1 levels under basal, stimulated, and ischemic conditions. 858 39

Peroxynitrite is a potent oxidant formed endogenously by the near diffusion-limited reaction of nitric oxide with superoxide anion. Peroxynitrite specifically adds a nitro group to the ortho position of the phenolic ring of free and protein-associated tyrosines to form the stable product 3-nitro-L-tyrosine. Systemic administration of 3-nitro-L-tyrosine markedly inhibits the subsequent hemodynamic responses to alpha 1- and beta-adrenoceptor agonists in anesthetized rats. Angiotensin II is an important modulator of vascular tone. The vasoconstrictor effects of this hormone are known to involve the release of catecholamines from sympathetic tissues. In the present study, we examined whether 3-nitro-L-tyrosine (2.5 mumol/kg i.v.) would attenuate the hemodynamic responses produced by angiotensin II (0.1-1.0 microgram/kg i.v.). Angiotensin II produced increases in mean arterial pressure, and renal and mesenteric vascular resistances, but no changes in hindquarter vascular resistance. The pressor and renal and mesenteric vasoconstrictor responses produced by angiotensin II were significantly attenuated 30-60 min following the administration of 3-nitro-L-tyrosine. Further attenuation of these responses was evident 120-180 min following the administration of 3-nitro-L-tyrosine. The alpha 1-adrenoceptor antagonist prazosin also diminished the pressor and renal and mesenteric vasoconstrictor responses produced by angiotensin II. These results demonstrate that 3-nitro-L-tyrosine inhibits the hemodynamic responses to angiotensin II, possibly through the inhibition of alpha 1-adrenoceptor-mediated events. The effect of 3-nitro-L-tyrosine on the hemodynamic action of angiotensin II raises the possibility that 3-nitro-L-tyrosine may be involved in the pathogenesis of the hemodynamic disturbances associated with inflammatory conditions, such as atherosclerosis, ischemia-reperfusion, and sepsis, where formation of peroxynitrite is favored.
 ...
PMID:The peroxynitrite product 3-nitro-L-tyrosine attenuates the hemodynamic responses to angiotensin II in vivo. 896 Aug 80

It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A2 (TXA2). The present study investigates in 6 healthy normotensive men whether prostaglandin H2-TXA2 receptor blockade with 100 mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o. influences angiotensin II-dependent peripheral regional vasoconstriction. Moreover, the regional balance of thromboxane B2 (TXB2), a stable metabolite of TXA2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral TXB2 balance was calculated from the respective arteriovenous plasma concentration differences and the corresponding regional plasma flow, the latter being determined by indocyanine-green dye, using appropriate catheterization techniques. Angiotensin II (0.2 microgram/min) induced a 66% increase in leg vascular resistance (p < 0.01) without affecting systemic hemodynamics. These regional hemodynamic effects of angiotensin II were not influenced by prostaglandin H2-TXA2 receptor blockade. Baseline TXB2 balance across the femoral vascular bed was equilibrated at slight extraction rates or around zero and remained unchanged during angiotensin II infusion. These results suggest that, in healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is not mediated by TXA2. Possible benefits of prostaglandin H2-TXA2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.
 ...
PMID:Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral vasoconstriction in healthy men: a pilot study. 914 8

Analysis of post-infarct ventricular remodeling consistently shows the accumulation of collagen in failing heart. The goal of this study was to gain insights into the underlying mechanisms of this event. We determined the effect of hypoxia, caused as the result of ischemia, on biological responses including cell viability, basal and growth factor-stimulated proliferative capacity and collagen type I production in cardiac fibroblasts obtained from adult human heart. The cell viability, as examined by light microscopy and analysis of DNA, did not change by hypoxia (2% oxygen). Basal level of protein synthesis, as determined by measuring the incorporation of 3H-leucine, decreased (30%, P<0.05) under hypoxia. Transforming growth factor-beta (TGF-beta1)- and thyroid hormone (T3)-induced increases in protein synthesis did not change under hypoxia. In contrast, basic fibroblast growth factor (bFGF)-stimulated protein synthesis enhanced significantly under hypoxia. Angiotensin II (Ang II)-treatment, which did not induce significant changes in protein synthesis under ambient conditions, led to moderate but significant increase under hypoxia. Basal level of DNA synthesis, as determined by measuring the incorporation of 3H-thymidine into DNA, decreased (32%, P<0.05) under hypoxia. The TGF-beta1-induced inhibition of DNA synthesis which was observed under ambient conditions was reversed [61% (P<0.005) increase under hypoxia]. Under ambient conditions, T3, Ang II and bFGF stimulated DNA synthesis and their effects were enhanced under hypoxia. Northern analysis showed a 46% (P<0.05) increase in the level of pro alpha1(l) collagen mRNA under hypoxia. The TGF-beta1-induced increase in the level of pro alpha1(l) collagen mRNA, under ambient conditions, was not observed under hypoxia. On the other hand, the T3-induced decrease in pro alpha1(l) collagen mRNA was reversed under hypoxia. Ang II- and bFGF-treatment of human cardiac fibroblasts did not cause detectable changes in the level of pro alpha1(l) collagen mRNA under ambient conditions or hypoxia. At the protein level, the amount of immunoreactive collagen type I, as determined by immunoslot blot analysis, was increased (33%, P<0.05) under hypoxia. Treatment of human cardiac fibroblasts with TGF-beta1 and T3 under ambient conditions led to diminished level of collagen type I. Under hypoxia, however, effect of both factors was reversed. The level of immunoreactive collagen type I in Ang II- and bFGF-treated cells, which was comparable to that in untreated cells under ambient conditions, remained unchanged under hypoxia. Together, these results provide evidence that hypoxia regulates growth, proliferative capacity and collagen type I production in human cardiac fibroblasts, and that although hypoxia alone may not be a stimulus for human cardiac fibroblast proliferation, it enhances growth factor-induced DNA synthesis in those cells. Furthermore, hypoxia by increasing the basal levels of collagen type I and by reversing the TGF-beta1- and T3-induced inhibition of collagen type I gene expression in human cardiac fibroblasts can enhance overall collagen type I production. Combinatorial effects of hypoxia on proliferation and collagen type I production in cardiac fibroblasts contribute to the post-infarct remodeling of the collagen matrix in failing human heart.
 ...
PMID:Hypoxia regulates basal and induced DNA synthesis and collagen type I production in human cardiac fibroblasts: effects of transforming growth factor-beta1, thyroid hormone, angiotensin II and basic fibroblast growth factor. 928 54

The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models. I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat.
 ...
PMID:An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. 940 46


1 2 3 4 5 6 7 8 Next >>