Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that microinjection of angiotensin II into the anterior hypothalamic area (AHA) produces a pressor response in rats and that the angiotensin AT1 receptor antagonist, losartan, similarly injected causes a depressor response in hypertensive rats. In this study, we examined whether endogenous angiotensins are involved in activation of neurons in the AHA. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure-ejected application of angiotensin II and glutamate onto some neurons in the AHA increased their firing rate. The increase of unit firing induced by angiotensin II but not by glutamate was inhibited by losartan. Application of losartan alone inhibited the basal firing rate of angiotensin II-sensitive neurons in a concentration-dependent manner. Application of the angiotensin AT2 receptor antagonist, PD123319, did not affect the increase of unit firing induced by angiotensin II and the basal firing rate of angiotensin II-sensitive neurons. Pressure application of angiotensin I onto angiotensin II-sensitive neurons also increased firing rate and the increase of unit firing by angiotensin I was inhibited by the angiotensin converting enzyme inhibitor, captopril. Captopril alone inhibited the basal firing rate of angitensin II-sensitive neurons. Acetylcholine did not affect unit firing of angiotensin II-sensitive neurons, whereas it increased the firing rate of some angiotensin II-insensitive neurons in the AHA. Increases of blood pressure by intravenous phenylephrine completely inhibited the basal firing rate of angiotensin II-sensitive neurons. These findings suggest that some neurons in the AHA are tonically activated by endogenous angiotensins. It seems likely that newly synthesized angiotensins are used for the angiotensinergic transmission in the AHA.
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PMID:Tonic angiotensinergic inputs to neurons in the anterior hypothalamic area of rats. 1505 24

Several large clinical trials have demonstrated that successful control of blood pressure decreases the incidence of strokes. Also, drugs that stimulate the production of angiotensin II, such as diuretics, calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs), provide additional stroke reduction than drugs that suppress angiotensin II production such as beta-blockers and angiotensin converting enzyme (ACE) inhibitors. Since the stroke-protective effect of angiotensin II is mediated through stimulation of the AT2 receptors, drugs that selectively block the AT1, such as the ARBs, provide greater stroke protection than the other antihypertensive drugs. The blockade of the AT1 receptors lessens local brain ischemia, whereas the stimulation of the AT2 receptors increases local blood flow through recruitment of collateral vessels. Among the ARBs, losartan possesses certain unique properties not shared by other members of its class, which enhance its stroke-protective effects. These include the prevention of platelet adhesiveness and aggregation and the decrease of serum uric acid levels, which both lead to reduction in cardiovascular and cerebrovascular events. (
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PMID:Stroke prevention with losartan in the context of other antihypertensive drugs. 1553 51

Angiotensin II is a multi-functional bioactive peptide and recent reports have suggested that angiotensin II is a proangiogenic growth factor. A retrospective cohort study revealed that angiotensin converting enzyme inhibitors decreased cancer risk, however, the precise mechanism is unknown. We hypothesized that endogenous angiotensin II plays a crucial role in tumor-associated angiogenesis. Tumors implanted in the subcutaneous tissue of wild-type mice developed intensive angiogenesis with vascular endothelial growth factor (VEGF) induction in tumor stroma. AT1a receptor (AT1a-R), but not AT1b receptor or AT2 receptor was expressed in tumor stroma and systemic administration of an AT1-R antagonist reduced tumor-associated angiogenesis and VEGF expression in tumor stroma. Angiotensin II up-regulates VEGF expression through the pathway including protein kinase C, AP-1 and NF-kappaB in fibroblasts, the major cellular component of tumor stroma. VEGF is a major determinant of tumor-associated angiogenesis in the present model, since angiogenesis was markedly reduced by either a VEGF neutralizing antibody or a VEGF receptor kinase inhibitor. Compared with the wild-type, tumor-associated angiogenesis was reduced in AT1a-R null mice, with reduced expression of VEGF in the stroma, and this reduction in AT1a-R null mice was not inhibited by an AT1-R antagonist. These suggest that host stromal VEGF induction by AT1a-R signaling is a key regulator of tumor-associated angiogenesis and tumor growth. AT1a-R signaling blockade may be a novel and effective therapeutic strategy against cancers.
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PMID:Angiotensin type 1a receptor signaling-dependent induction of vascular endothelial growth factor in stroma is relevant to tumor-associated angiogenesis and tumor growth. 1563 93

The use of ACE inhibitors (ACE-i) represents an Ia recommendation in the treatment of patients with STEMI and NSTEMI. However, results of smaller studies suggest an increase of in-stent-restenosis under ACE-i administration. The effects of ACE-i and valsartan after bare metal stent implantation of the culprit type B2/C lesion should be compared. Seven hundred patients were treated either by ACE-i in cases of LVEF<50% or 80 mg valsartan in cases of LVEF> or =50%. Restenosis rates after 6 months were analysed in 399 patients under valsartan and 224 patients under ACE-i with control angiography and major adverse cardiac events (death, infarction, reintervention) in a follow-up of up to 4 (mean 2.6) years in all patients. In-stent-restenosis was found in 19.5% under valsartan and in 34% under ACE-i (p<0.005). In diabetic patients, restenosis occurred in 24% under valsartan and in 43% under ACE-i (p<0.01). In initial acute coronary syndrome (ACS), restenosis rate was 14% under valsartan and 43% under ACE-i (p<0.0001). In stable angina, restenosis rates were 26.5% and 27.5%, respectively. Total MACE rates revealed significant differences in ACS due to reintervention rates of 22% and 7% under ACE-i and valsartan (p<0.0001). The administration of 80 mg valsartan after bare metal stent implantation leads to a reduction of in-stent-restenosis compared to ACE-i. This effect is mainly due to beneficial effects of valsartan in cases with initial ACS. Major differences between ACE-i and valsartan are discussed including inflammation, activation of neutrophils, mode of bradykinin activation, AT2 receptor stimulation and apoptosis of smooth muscle cells.
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PMID:Valsartan versus ACE inhibition after bare metal stent implantation--results of the VALVACE trial. 1568 87

Pregnant ewes were fed either a 50% nutrient-restricted (NR; n= 8) or a control 100% (C; n= 8) diet from day 28 to day 78 of gestation (dGA; term = 150 dGA). Lambs were born naturally, and fed to appetite throughout the study period. At 245 +/- 1 days postnatal age (DPNA), offspring were instrumented for blood pressure measurements, with tissue collection at 270 DPNA. Protein expression was assessed using Western blot, glomerulus number determined via acid maceration and hormone changes by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). NR lambs had higher mean arterial pressure (MAP; 89.0 +/- 6.6 versus 73.4 +/- 1.6 mmHg; P < 0.05), fewer renal glomeruli (57.8 +/- 23.8 versus 64.6 +/- 19.3 x 10(4); P < 0.05), increased expression of angiotensin converting enzyme (ACE) in the renal cortex (942 +/- 130 versus 464 +/- 60 arbitrary pixel units (apu); P < 0.03), and increased angiotensin II receptor AT2 expression in the renal medulla (63.3 +/- 12.1 versus 19.5 +/- 44.2 x 10(4) apu; P < 0.03). All data are presented as mean +/-S.E.M. The present data indicate that global maternal nutrient restriction (50%) during early to mid-gestation impairs renal nephrogenesis, increases MAP, and alters expression of AT2 and ACE without an associated change in birth weight. These data demonstrate the existence of a critical window of fetal susceptibility during early to mid-gestation that alters kidney development and blood pressure regulation in later life.
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PMID:Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age. 1579 Jun 63

Blockade of the renin-angiotensin system (RAS) is now recognised as an effective approach for the treatment of hypertension and congestive heart failure (CHF). Today, it is possible to antagonise the effects of angiotensin II more specifically by blocking its receptors using non-peptide receptor antagonists. These compounds, which at first were used to identify the various subtypes of angiotensin II receptors, are now available clinically. Some of them have recently been launched on the market and several others are preregistered for the treatment of hypertension. These new molecules are as effective as angiotensin converting enzyme (ACE) inhibitors at lowering blood pressure in hypertensive patients, and appear to have similar systemic and renal haemodynamic properties in patients with CHF and renal diseases. Large-scale clinical trials such as the LIFE, the ELITE and the RENAAL studies are now underway to investigate the long-term benefits of one of these agents in hypertension, heart failure and Type II diabetic nephropathy. The major clinical advantage of AT1 receptor antagonists is that, in contrast to ACE inhibitors, they do not induce cough. With the more widespread use of AT1 receptor antagonists, two unresolved questions remains unanswered: what is the role of AT2 receptors? Are the unblocked effects of angiotensin II on AT2 receptor sites of any clinical relevance to the safety profile or efficacy of AT1 receptor antagonists? Another interesting question is whether the combination of an ACE inhibitor with an AT1 receptor antagonist is advantageous. Studies attempting to answer these questions are underway and will certainly enable researchers to define more precisely the role and the advantages of these new specific non-peptide AT1 receptor antagonists in the treatment of hypertension and heart failure.
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PMID:Angiotensin II receptor antagonists - antihypertensive agents. 1598 15

Current understanding of the genesis of diabetic vascular disease suggests that vascular complications, such as atherosclerosis and hypertension, are associated with changes in structural and functional parameters. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in the development of micro- and macro-vascular complications. Most of the negative cardiovascular actions of angiotensin II are mediated through AT1 receptors, whereas the AT2 receptors mediate largely beneficial effects. Hence, compared to angiotensin converting enzyme inhibitors (ACEIs), selective AT1 receptor blockers (ARBs) should provide additional end organ protection via AT2 receptors activation. Although ACEIs are useful therapeutically, they are being currently displaced by ARBs. Enhanced calcium ion channel activity is reported in vascular smooth muscles from diabetic animal models. Clinical benefits of calcium channel blockers (CCBs) in diabetic hypertensive patients are controversial, but there is increasing experimental evidence for the beneficial effects of dihydropyridine-type CCBs. Although the treatment of hypertension in diabetics reduces cardiovascular and microvascular complications, the ideal strategy for treating hypertension in diabetics has not been well defined and warrants a combination approach. Only limited clinical data regarding the use of ARBs in combination with CCBs in diabetics are available. The experimental data suggest that combination of a CCB and an AT1 receptor blocker, or a hypothetical dual blocker of AT1 receptors as well as of calcium channels would be an ideal regimen. There is, however, no conclusive clinical evidence to support the combined use of these drugs. This review highlights the available experimental data that support the therapeutic benefits of this combination.
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PMID:Saga of renin-angiotensin system and calcium channels in hypertensive diabetics: does it have a therapeutic edge? 1600 28

Our purpose was to observe the effects of sodium phosphate (NaP) colonoscopy preparation on serum electrolytes, phosphate, and calcium and to identify factors associated with any adverse effects. In an unselected group of 100 consecutive patients attending for out patient colonoscopy, 45% of patients had raised serum phosphate, which was positively correlated with creatinine and age. There was a negative association of phosphate with calcium; 16% of patients had hypocalcemia and 26% had hypokalemia. Patients taking ACE inhibitors, AT2 antagonists, or diuretics were associated with hyperphosphatemia. Significant electrolyte and metabolic disturbance from colonoscopy preparation has been shown with NaP preparation, without overt clinical effects. We recommend that elderly patients and those with significant comorbidity have their electrolytes and calcium measured, and diuretics and ACE inhibitors stopped, before NaP administration. Endoscopy units should be alert for patients who might be suffering from electrolyte disturbance postpreparation and be prepared to measure their electrolytes.
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PMID:Measurement of serum electrolytes and phosphate after sodium phosphate colonoscopy bowel preparation: an evaluation. 1604 80

Diabetes mellitus, arterial hypertension, smoking are major stroke risk factors. The role of hypercholesterolemia in stroke has not been established yet. In patients with type 2 diabetes mellitus there is evidence that intensive glucose lowering therapy diminishes the risk of microvascular complications. In all patients with stroke or transient ischemic attack (TIA), blood pressure should be lowered irrespectively of the baseline level with either diuretics, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, or calcium antagonists. The role of angiotensin II (AT2) receptor blockers has not been established so far. In general terms a global approach to management of patients with vascular risk factors should be developed. An extended follow-up of randomised trials on preventive therapy should be completed. Controlled trials comparing angiotensin receptor blockers with ACE inhibitors should be started. Further research may focus on the new lipid lowering agents, and on the comparison of single lipid lowering agent vs. combinations in stroke prevention. These efforts should help in finding the best vasoprotective strategy in stroke prevention.
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PMID:Antihypertensive and lipid lowering treatment in stroke prevention: current state and future. 1607 57

Losartan, the first angiotensin II receptor antagonist was introduced in 1994. Since then, five other antagonists have been launched for the management of hypertension. In recent years, numerous studies have demonstrated that angiotensin II antagonists are as effective as other antihypertensive agents but with a better tolerability profile. The challenge with these agents is now to demonstrate their potential benefits on morbidity and mortality, and several very large clinical trials are therefore running in hypertension, congestive heart failure and diabetic nephropathy. In addition, research is focusing intensively on defining the role of angiotensin AT2 receptors, and the potential benefits of combining ACE inhibitors and angiotensin II antagonists.
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PMID:Angiotensin II receptor antagonists: where do we stand? 1610 40


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