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

Experiments were performed to evaluate the hypothesis that the early stage of Type 1 diabetes mellitus (DM) increases renal angiotensin II (AngII) concentration and angiotensin type 1 (AT) receptor protein levels. Nineteen or twenty days after vehicle (Sham rats) or streptozotocin (STZ rats) treatment, plasma [AngII] was higher in STZ rats (152 +/- 23 fmol/ml) than in Sham rats (101 +/- 7 fmol/ml); however, kidney [AngII] did not differ between groups. AT1 receptor protein expression was greater in STZ kidneys than in Sham kidneys. This increase was restricted to the cortex, where AT1 protein levels were elevated by 77 +/- 26% (42 kDa) and 101 +/- 16% (58 kDa) in STZ kidneys. Immunohistochemistry revealed this effect to be most evident in distal nephron segments including the connecting tubule/cortical collecting duct. Increased renal cortical AT1 receptor protein and circulating AngII levels are consistent with an exaggerated AngII-dependent influence on renal function during the early stage of DM in the rat.
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PMID:Renal AT1 receptor protein expression during the early stage of diabetes mellitus. 1199 Dec 2

We investigated the effects of a 3-week treatment with various combinations of angiotensin-converting enzyme inhibitor (ACEI) and B1 and B2 bradykinin receptor (B1R and B2R) antagonists (B1A and B2A) and AT1 receptor antagonist on ERK 1 and 2 phosphorylation in isolated glomeruli from streptozotocin-treated diabetic rats (STZ rats). Body weight, glycemia, and blood pressure were monitored. The rats were divided into nine groups: (1) control; and groups 2-9 were STZ treated with (3) insulin, (4) ACEI, (5) ACEI + B1A, (6) ACEI + B2A, (7) B2A, (8) B1A, (9) AT1 antagonist. ERK 1 and 2 phosphorylation and expression of B1R and B2R were assessed by Western blot analysis. ERK 1 and 2 phosphorylation was higher in STZ rats; this activation was normalized by insulin and reduced by ACEI but not by AT1 antagonist. The reduction of ERK 1 and 2 phosphorylation by the ACEI was reversed by B1A and B2A. The induction of B1R was confirmed by increased expression of mRNA and B1 receptor protein. Since ERK 1 and 2 phosphorylation is an early event in the induction of matrix secretion and hyperproliferation associated with diabetic nephropathy, activation of B1R and B2R appears to be a useful pharmacological target in the management of this pathology.
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PMID:Induction of B1 receptors in streptozotocin diabetic rats: possible involvement in the control of hyperglycemia-induced glomerular Erk 1 and 2 phosphorylation. 1202 68

Treatment of rats with streptozotocin (STZ, 45mg/kg, i.v.,single dose) produced cardinal symptoms of diabetes mellitus including hyperglycemia, hypoinsulinemia and increase in blood pressure. Treatment with losartan--an angiotensin (AT1) receptor antagonist, 2 mg/kg, po for 6 weeks decreased the blood glucose levels by 16.5%. There was 190% increase in AUCglucose and 59.4% decrease in AUCinsulin in STZ-diabetic rats as compared to control rats. Treatment with losartan caused slight decrease in AUCglucose and slight increase in AUCinsulin. There was no significant difference in insulin sensitivity (K(ITT)) index of STZ-diabetic group as compared to control. Losartan treatment failed to alter these levels significantly. Serum cholesterol and creatinine levels were found to be increased significantly in STZ-diabetic rats. Treatment with losartan significantly prevented the rise in cholesterol and creatinine levels by 20.1 and 81% respectively. The results suggest that losartan produces some beneficial effects in STZ-diabetic rats.
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PMID:Effect of chronic treatment with losartan on streptozotocin induced diabetic rats. 1256 64

The objective of the present study is to investigate whether plasma insulin levels play a role in the antinatriuretic and vasoconstrictor actions of angiotensin-II (Ang-II). We evaluated antinatriuretic function of endogenous Ang-II using an AT1 receptor antagonist, candesartan in anesthetized Sprague-Dawley rats. In control rats, candesartan produced significant increases in natriuresis and diuresis and these effects were abolished in streptozocin (STZ, 55 mg/kg i.p.) treated rats. Replacement of insulin restored these renal effects of candesartan. In a separate group of rats pretreated with an autonomic ganglionic blocker, pressor responses to Ang-II and norepinephrine (NE) before or after L-NNA, a nitric oxide synthase inhibitor were not affected by STZ treatment. However, insulin replacement greatly augmented these responses. These data provide evidence in vivo showing that insulin can enhance both antinatriuretic and vasoconstrictor actions of Ang-II. Hence exaggerated renal and vascular effects of Ang-II in the obese Zucker rats observed in our previous studies may be related to hyperinsulimemia and this phenomena could contribute to salt-sensitivity and development of sustained hypertension.
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PMID:Influence of plasma insulin levels on antinatriuretic and vasoconstrictor actions of angiotensin-II. 1279 98

Elevated glucose concentration is implicated to play major role in development of diabetic associated vascular complications. It was previously reported that angiotensin II (Ang II) induced contractile response is enhanced in thoracic aorta of diabetic rats. In the present study, the effect of high glucose (HG, 25 mM) exposure for 2h on Ang II cumulative concentration response curves recorded isometrically was studied in thoracic aortic rings isolated from male Sprague-Dawley rats pretreated with streptozotocin (STZ, 65 mg kg(-1) i.p.) or vehicle at 8 weeks prior to the study. Ang II induced contraction via AT1 receptor was significantly enhanced (by 60 +/- 2 %) in HG exposed thoracic aortic rings isolated from vehicle treated but not STZ treated rats. However, there was no change in the pD2 of Ang II while potassium chloride (KCl) induced contraction was unaltered. Ang II induced contractile response was blocked by valsartan (100 microM, selective AT1 receptor antagonist) but not PD 123,319 (100 microM, selective and potent AT2 receptor antagonist). Exposure of aortic rings from control rats to 25 mM mannitol or sucrose for 2 h did not have any effect on the Ang II induced contraction. Tempol (100 microM, a cell permeable superoxide dismutase mimetic) partially reduced the augmented Ang II response in HG exposed aortic rings, while it did not affect the Ang II responses in normal glucose (NG 5.5 mM) exposed aortic rings isolated from control rats. [3H] Ang II binding at AT1 receptors was unaltered in vascular smooth muscle membranes prepared from thoracic aorta exposed to HG for 2 h compared to NG exposed aortic rings. From our results, we conclude that high glucose concentration augments Ang II mediated contraction via AT1 receptors and reactive oxygen species partly contribute to this augmented contraction.
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PMID:High glucose concentration augments angiotensin II mediated contraction via AT1 receptors in rat thoracic aorta. 1550 93

Several enzymatic sources of reactive oxygen species (ROS) were described as potential reasons of eNOS uncoupling in diabetes mellitus. In the present study, we investigated the effects of AT1-receptor blockade with chronic telmisartan (25 mg/kg/day, 6.5 weeks) therapy on expression of the BH4-synthesizing enzyme GTP-cyclohydrolase I (GCH-I), eNOS uncoupling, and endothelial dysfunction in streptozotocin (STZ, 60 mg/kg iv, 7 weeks)-induced diabetes mellitus (type I). Telmisartan therapy did not modify blood glucose and body weight. Aortas from diabetic animals had vascular dysfunction as revealed by isometric tension studies (acetylcholine and nitroglycerin potency). Vascular and cardiac ROS produced by NADPH oxidase, mitochondria, eNOS, and xanthine oxidase were increased in the diabetic group as was the expression of NADPH oxidase subunits at the protein level. The expression of GCH-I and the phosphorylation of eNOS at Ser1177 was decreased by STZ treatment. Therapy with telmisartan normalized these parameters. The present study demonstrates for the first time that AT1-receptor blockade by telmisartan prevents downregulation of the BH4 synthase GCH-I and thereby eNOS uncoupling in experimental diabetes. In addition, telmisartan inhibits activation of superoxide sources like NADPH oxidase, mitochondria, and xanthine oxidase. These effects may explain the beneficial effects of telmisartan on endothelial dysfunction in diabetes.
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PMID:AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats. 1853 57

The Renin-angiotensin system, besides blood pressure regulation, affects learning and memory as evidenced by improvement of cognition in hypertensive patients being treated with AT1 receptor blockers like candesartan. The present study examined the influence of candesartan on memory impairment induced by intracerebral streptozotocin (IC STZ 0.5 mg/kg) in mice. Candesartan (0.05 mg/kg and 0.1 mg/kg, i.p.) was given for 14 days following IC STZ administration. The dose of 0.1 mg/kg significantly improved latency period in passive avoidance test. Further, treatment with 0.1 mg/kg candesartan for 14 days significantly improved spatial memory in mice in water maze test also. In another group, after memory impairment in mice following IC STZ administration, memory improving effect of a 7 days treatment with 0.1 mg/kg candesartan lasted only for 3 subsequent days in water maze task. IC STZ increased oxidative stress but pretreatment with 0.1 mg/kg candesartan decreased oxidative stress as indicated by a decrease in MDA and increase in GSH. Further, candesartan decreased free radicals as evidenced by flow cytometry. IC STZ affected cholinergic system also by increasing acetylcholine esterase activity that was restored by pretreatment with 0.1 mg/kg candesartan. Locomotor activity and serum glucose level remained unaffected by candesartan treatment. These results suggest that AT1 receptors play a facilitatory role in STZ induced memory deficit and corroborate number of human studies that AT1 receptor blockers can be used therapeutically against cognitive decline in hypertensive patients.
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PMID:Candesartan improves memory decline in mice: involvement of AT1 receptors in memory deficit induced by intracerebral streptozotocin. 1910 28

Glomerular filtration rate is controlled by the contractile effect of angiotensin II on afferent and efferent arterioles. The renin positivity of the afferent arterioles depends on tubuloglomerular feedback via the macula densa (MD) and short loop feedback via the afferent arteriolar endothelia. The renin-producing cells are trans-differentiated from smooth muscle cells (SMCs) of mainly the afferent arterioles, the MD cells are trans-differentiated from the neighboring tubular cells, and the high-permeability endothelial cells are trans-differentiated from normal permeability endothelial cells facing the renin-negative part of the afferent arterioles. All of the trans-differentiations depend on the activity of the renin-angiotensin system (RAS). The distribution of AT1 receptors for angiotensin II expresses the contractile effects of angiotensin II on renin-negative SMCs and the negative effect on trans-differentiation of renin-positive SMCs and MD cells. The purpose of this review is to summarize the stereological data of molecules like angiotensin II AT1 receptors, L-type calcium channels, and renin receptors in the juxtaglomerular apparatus of normal and STZ-induced diabetic rat kidneys, thus showing their functional relevancies on trans-differentiation among the juxtaglomerular apparatus' elements.
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PMID:Functional Relevancies of Trans-Differentiation in the Juxtaglomerular Apparatus of Rat Kidney. 3260 89