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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain contains both angiotensin II (Ang II) type 1 (AT1) and Ang II type 2 (AT2) receptors. Neuronal AT1 receptors mediate the stimulatory actions of Ang II on blood pressure, water and salt intake, and secretion of vasopressin. In contrast, neuronal AT2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic to AT1 receptors. The physiological actions of Ang II in the brain, whether mediated by AT1 or AT2 receptors, involve changes in neuronal activity that are initiated by changes in the activity of membrane ionic currents and channels. This review focusses on the intracellular signalling pathways that couple neuronal AT1 and AT2 receptors to changes in the activity of membrane K+ and Ca2+ currents and channels. As will become clear from our discussion, the signalling pathways that are modulated by neuronal AT1 and AT2 receptors are quite distinct.
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PMID:Neuronal ion channel signalling pathways: modulation by angiotensin II. 969 73

The neuropeptides angiotensin II (AngII) and oxytocin (OT) play important but opposing roles in the regulation of sodium appetite in the rat, AngII as a stimulatory peptide and OT as an inhibitory peptide. Adrenal steroids increase the density of AngII receptors in brain following in vivo administration, although the neuroanatomical and subtype specificity have not been thoroughly examined. Furthermore, previous studies demonstrate that adrenalectomy (ADX) leads to a reduction in OT receptors, although regions associated with sodium appetite remain to be examined. In the present study, quantitative receptor autoradiography was used to locate regions where perturbations in circulating adrenal steroids affect the density of oxytocin receptors and the angiotensin receptor subtypes AT1 and AT2. The results show that ADX results in a small, but significant decrease in AT1 expression in the paraventricular nucleus of the hypothalamus, subfornical organ, and the area postrema. That this effect is reversed by either aldosterone or low-dose corticosterone replacement suggests that occupancy of the mineralocorticoid receptor is responsible for the steroid effect. No changes were observed in AT2 or OT receptors in nuclei associated with sodium appetite, indicating that perturbations in adrenal steroids did not affect these receptors in brain regions implicated in the control of salt appetite.
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PMID:Adrenal steroid regulation of central angiotensin II receptor subtypes and oxytocin receptors in rat brain. 975 19

1. Early studies suggest that hypertension in Dahl salt-sensitive (S) rats is related to an uncommon humoral factor that may be released from the kidney. 2. To investigate whether the kidney releases a hypertensinogenic factor for developing salt-induced hypertension in S rats, we examined a pressor effect, or vascular contractive activity of a kidney extract from S rats using a conscious recipient rat or an isolated aortic ring. 3. Donor S and Dahl salt-resistant (R) rats were fed a 0.4 or 8% NaCl diet for 4 weeks and were then used to provide four kinds of kidney extracts (S-0.4%, S-8%, R-0.4%, R-8%). The systolic arterial pressure (SAP) was significantly increased in donor S rats fed an 8% NaCl diet compared with other donor rat groups. 4. All four types of kidney extract increased mean arterial pressure (MAP) in a recipient rat fed a 0.4% NaCl diet. However, the increase in MAP observed following infusion of the S-8% extract was the least of all groups. An angiotensin AT1 receptor antagonist, CV-11974, abolished any pressor effect of all kidney extracts. In an in vitro experiment, all four types of kidney extract evoked contractile responses in aortic rings, but elicited no significant difference in aortic ring contractile force. 5. These results suggest that the kidney of S rats may not release an active hypertensinogenic factor that would cause salt-induced hypertension.
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PMID:Is a hypertensinogenic factor present in the kidney of hypertensive dahl rats? 978 19

We studied the effects of chronic blockade of the renin-angiotensin system on hypertension and cardiac left ventricular hypertrophy (LVH) in Dahl salt-sensitive (DS) rats given a high-salt or low-salt diet. [Experiment 1] Twelve-week-old male DS rats were fed an 8% NaCl diet and received the angiotensin II receptor (AT1) antagonist, candesartan (3 mg/kg/d), the angiotensin converting enzyme inhibitor enalapril (30 mg/kg/d), or vehicle for 6 wk after 3 wk of 8% salt-loading. Neither candesartan nor enalapril with concomitant high salt-loading attenuated the blood pressure (BP) elevation. LVH was also not attenuated significantly by these treatments. [Experiment 2] After 8 wk of 8% salt-loading, the rats were given a 0.3% NaCl diet and concurrently received candesartan, enalapril, or vehicle for 5 wk. Switching from the high-salt to low-salt diet significantly decreased BP and left ventricular mass in the vehicle-treated animals. Both candesartan and enalapril normalized BP during salt-depletion; the blockade of the renin-angiotensin system produced an additive reduction in LVH. These findings suggest that sodium intake and hemodynamic load, but not the renin-angiotensin system, may be major determinants of the development of LVH in DS rats.
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PMID:Effects of renin-angiotensin system blockade and dietary salt intake on left ventricular hypertrophy in Dahl salt-sensitive rats. 978 99

The anterior ventral third ventricle (AV3V) region of the brain contains high concentrations of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) that are important in the maintenance of body fluid and electrolyte balance as well as other physiological processes. Daily intracerebroventricular pulse injections of MR antisense oligonucleotides significantly suppressed deoxycorticosterone acetate (DOCA) induced salt appetite in a dose-related manner. Similar administration of GR antisense or scrambled/sense oligonucleotide into the third ventricle failed to inhibit salt appetite. Salt appetite aroused after adrenalectomy was not suppressed by MR antisense oligonucleotide treatments but was suppressed by an antisense oligonucleotide directed against the angiotensin II AT1 receptor subtype. Receptor binding analysis demonstrated that MR and GR oligonucleotide treatments each reduced their respective receptor subtypes. Finally, although GR antisense oligonucleotide treatment was ineffective in suppressing DOCA-induced salt appetite, this treatment did increase stress induced corticosterone release as well as delayed the recovery of corticosterone to basal levels after stress.
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PMID:Intracerebroventricular Administration of Mineralocorticoid Receptor Antisense Oligonucleotides Attenuates Salt Appetite in the Rat. 978 54

The natriuretic peptide (NP) system is one of the most important systems regulating blood pressure and body-fluid homeostasis. The biological activities of the system are determined by the NPs and the receptors, which are comprised of three subtypes: NP-AR and NP-BR related to biological activities and NP-CR related to the clearance of NP. We focused our studies on the receptor subtypes. In hypertensive rats (SHR-SP/Izm, DOCA/salt), NP-AR was upregulated and NP-CR was downregulated. The ACE inhibitor derapril, but not the Ca2+ blocker manidipine, normalized the upregulated NP-AR, but the effect was completely abolished by the bradykinin beta 2-receptor antagonist, suggesting that bradykinin regulates the vascular NP-AR. The AT1 antagonist TCV-116, but not manidipine, reversed the downregulated NP-CR. Ang II decreased NP-CR in cultured aortic smooth muscle cells. These results suggest that upregulation of NP-AR and downregulation of NP-CR with the increased plasma NPs counteract hypertension by enhancing the action of NP. A beta-blocker (carvedilol) potentiated the hypotensive action of NPs by increasing plasma NPs and enhancing the vascular response to NPs via downregulation of the vascular and lung NP-CR. The newly found mode of actions could be related to its anti-heart failure effect. In genetically hyperglycemic Wistar fatty rats, vascular NP-BR and NP-AR were upregulated. Since plasma ANP and vascular CNP were significantly increased, the local CNP/NP-BR system as well as the systemic ANP/NP-AR system may play an important role in counteracting vascular remodeling in diabetes mellitus. All these observations provide in vivo evidence for the pathophysiological significance of the receptor subtype of the NPs.
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PMID:[Pathophysiological significance of the natriuretic peptide system: receptor subtype as another key factor]. 979 68

N-(3',4'-dimethoxycinnamoyl) anthranilic acid (tranilast), an effective anti-allergic drug, has successfully prevented restenosis in patients who have undergone percutaneous transluminal coronary angioplasty. To elucidate the mechanism of tranilast, we investigated its antagonistic effect to angiotensin II, which plays a pivotal role in the proliferation of vascular smooth muscle cells, using angiotensin II-induced contractions in human gastroepiploic artery and rabbit aorta. The possible antagonistic effects of other anti-allergic agents such as 4-( p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthal azinone hydrochloride (azelastine), 9-methyl-3-( 1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyramidin-4-one potassium salt (pemirolast) and disodium cromoglycate were also compared. Tranilast dose-dependently inhibited the angiotensin II-induced contractions in human and rabbit arteries (IC50 = 3.6x10(-5) M and pD'2 = 3.69, respectively). Pemirolast showed a weak antagonistic effect to angiotensin II, but the effective concentration cannot be administered in clinical dosage. Tranilast and pemirolast had no effect on the concentration-contractile response curves for KCI and norepinephrine. Azelastine inhibited angiotensin II-, KCl- and norepinephrine-induced contractions non-specifically, while disodium cromoglycate did not affect these contractile responses. Tranilast but not azelastine showed synergistic action with 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimi dazole-7-carboxylic acid (CV- 11974) in antagonizing angiotensin II-induced contraction and the inhibitory pattern was similar to that of the non-peptide angiotensin II AT1 receptor antagonist CV-11974. These findings indicate that only tranilast possesses the unique ability to antagonize angiotensin II in clinical dosage, which may contribute at least in part to prevention of restenosis after percutaneous transluminal coronary angioplasty.
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PMID:Tranilast, an anti-allergic drug, possesses antagonistic potency to angiotensin II. 986 9

We investigated the effect of angiotensin-converting enzyme inhibition on spontaneous nephrosis in Dahl salt-sensitive (Dahl/S) rats. Dahl/S rats fed on a normal sodium diet spontaneously developed nephrosis and mild hypertension from a young age. In young Dahl/S rats, an angiotensin-converting enzyme inhibitor, imidapril, attenuated the development of proteinuria accompanied by a decrease in blood pressure. Methylprednisolone, a potent therapeutic agent for proteinuria, did not affect the development of nephrosis. An angiotensin AT1 receptor antagonist, losartan, but not a Ca2+ channel blocker, verapamil, inhibited the development of nephrosis while both agents decreased blood pressure to a similar extent as imidapril. In mature Dahl/S rats, imidapril suppressed not only the development of proteinuria but also the glomerular lesions. It is concluded that the development of spontaneous nephrosis in Dahl/S rats is mediated by angiotensin II.
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PMID:Involvement of angiotensin II in development of spontaneous nephrosis in Dahl salt-sensitive rats. 987 73

Pharmacologic interruption of the renin-angiotensin system has played a crucial role in determining its contribution to physiology, pathophysiology, and has made an enormous contribution to therapeutics. Despite this record of success, no pharmacologist would have chosen the angiotensin-converting enzyme (ACE) step for pharmacologic blockade. As renin is rate-limiting in the cascade and has remarkable specificity for its substrate, renin inhibition would have made a far more attractive target. Indeed, evidence reviewed in this article supports this case. A renin inhibitor developed to block rat renin produced a larger reduction in plasma angiotensin II concentration than did two ACE inhibitors at the top of their dose-response relationship. In humans, renin inhibition led to a larger increase in renal plasma flow in healthy human volunteers studied on a low salt diet to activate the renin system than did ACE inhibitors. Again, the studies used doses in each case at the top of the dose-response relationships for renal hemodynamics. Because the response to AT1 receptor blockade was very similar to the response induced by renin inhibitors, the results suggest that both classes of agent acted via their influence on the renin system. Moreover, the data suggest that 30 to 40% of angiotensin II formation influencing the kidney in the healthy human during renin system activation is formed via renin-dependent, but ACE-independent, pathways. These findings have potentially important therapeutic implications, and certainly help to justify the major therapeutic trials now ongoing and planned.
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PMID:Pharmacologic interruption of the renin-angiotensin system and the kidney: differential responses to angiotensin-converting enzyme and renin inhibition. 989 71

The renin-angiotensin system (RAS) plays an important role in blood pressure control and in water and salt homeostasis. It is involved in the pathophysiology of hypertension and structural alterations of the vasculature, kidney, and heart, including neointima formation, nephrosclerosis, postinfarction remodeling, and cardiac left ventricular hypertrophy (LVH). Recently, an increased knowledge of the effector peptides of the RAS, their receptors, and their respective functions has led to a new principle of treatment for hypertension: the inhibition of angiotensin (Ang) II via angiotensin-converting enzyme inhibitors or Ang II-receptor antagonists. In this review, the Ang receptors AT1 and AT2 and the potential roles of shorter angiotensin fragments, including Ang III(2-8), Ang IV(3-8), and Ang(1-7), are discussed.
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PMID:The renin-angiotensin system and its receptors. 1002 50


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