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

Responses to the synthetic substrate [Pro11,D-Ala12]angiotensin I were investigated in the hindlimb vascular bed of the cat, a system in which local angiotensin-converting enzyme activity is high. Under constant-flow conditions, injections of [Pro11,D-Ala12]angiotensin I into the perfusion circuit in doses of 1-300 micrograms caused dose-related increases in perfusion pressure that were rapid in onset and that were not changed by the presence of a time-delay coil in the perfusion circuit upstream from the site of peptide injection. The synthetic substrate was approximately 100-fold less potent than angiotensin I and II, and responses to [Pro11,D-Ala12]angiotensin I were not altered by captopril in a dose that inhibited pressor responses to angiotensin I but did not alter responses to angiotensin II. Responses to [Pro11,D-Ala12]angiotensin I, angiotensin I, and angiotensin II were inhibited by DUP-532 and candesartan but were not altered by the angiotensin AT2 receptor antagonist PD-123319. The present data show that [Pro11,D-Ala12]angiotensin I has significant vasoconstrictor activity in the hindlimb vascular bed of the cat and suggest that responses are mediated by the activation of AT1 receptors and that activation of AT2 receptors is not involved. The present data show that the onset of responses to [Pro11,D-Ala12]angiotensin I and angiotensin II are similar and are not dependent on the action of the angiotensin-converting enzyme. The present data suggest that conversion of the synthetic substrate to an active peptide occurs rapidly within the hindlimb vascular bed or that the peptide may have direct AT1 receptor-stimulating activity.
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PMID:[Pro11,D-Ala12]angiotensin I has rapid onset vasoconstrictor activity in the cat. 943 19

We investigated the regulation of the Ca(2+)-activated K+ (maxi-K+) channel by angiotensin II (ANG II) and its synthetic analog, [Lys2]ANG II, in freshly dispersed intestinal myocytes. We identified a maxi-K+ channel population in the inside-out patch configuration on the basis of its conductance (257 +/- 4 pS in symmetrical 150 mM KCl solution), voltage and Ca2+ dependence of channel opening, low Na(+)-to-K+ and Cl(-)-to-K+ permeability ratios, and blockade by external Cs+ and tetraethylammonium chloride. ANG II and [Lys2]ANG II caused an indirect, reversible, Ca(2+)- and dose-dependent activation of maxi-K+ channels in cell-attached experiments when cells were bathed in high-K+ solution. This effect was reversibly blocked by DUP-753, being that it is mediated by the AT1 receptor. Evidences that activation of the maxi-K+ channel by ANG II requires a rise in intracellular Ca2+ concentration ([Ca2+]i) as an intermediate step were the shift of the open probability of the channel-membrane potential relationship to less positive membrane potentials and the sustained increase in [Ca2+]i in fura 2-loaded myocytes. The preservation of the pharmacomechanical coupling of ANG II in these cells provides a good model for the study of transmembrane signaling responses to ANG II and analogs in this tissue.
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PMID:Activation of Ca(2+)-activated K+ (maxi-K+) channel by angiotensin II in myocytes of the guinea pig ileum. 957 95

Cell pH was monitored in medullary thick ascending limbs to determine effects of ANG II on Na(+)-K+(NH4+)-2Cl- cotransport. ANG II at 10(-16) to 10(-12) M inhibited 30-50% (P < 0.005), but higher ANG II concentrations were stimulatory compared with the 10(-12) M ANG II level cotransport activity; eventually, 10(-6) M ANG II stimulated 34% cotransport activity (P < 0.003). Inhibition by 10(-12) M ANG II was abolished by phospholipase C (PLC), diacylglycerol lipase, or cytochrome P-450-dependent monooxygenase blockade; 10(-12) M ANG II had no effect additive to inhibition by 20-hydroxyeicosatetranoic acid (20-HETE). Stimulation by 10(-6) M ANG II was abolished by PLC and protein kinase C (PKC) blockade and was partially suppressed when the rise in cytosolic Ca2+ was prevented. All ANG II effects were abolished by DUP-753 (losartan) but not by PD-123319. Thus < or = 10(-12) M ANG II inhibits via 20-HETE, whereas > or = 5 x 10(-11) M ANG II stimulates via PKC Na(+)-K+(NH4+)-2Cl- cotransport; all ANG II effects involve AT1 receptors and PLC activation.
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PMID:ANG II controls Na(+)-K+(NH4+)-2Cl- cotransport via 20-HETE and PKC in medullary thick ascending limb. 957 2

The subfornical organ and organum vasculosum laminae terminalis represent neuroglial circumventricular organ structures bordering the anterior third cerebral ventricle. Owing to the absence of the blood-brain barrier, the cellular elements of the subfornical organ and the organum vasculosum laminae terminalis can be reached by circulating messenger molecules transferring afferent information. As demonstrated for the control of extracellular fluid composition, the circulating hormone angiotensin II acts on these sensory circumventricular organs to induce drinking, elevated peripheral resistance and neurohypophyseal hormone release via interaction with membrane-spanning receptor proteins. To characterize the cell-specific distribution of angiotensin II receptors within the circumventricular organs, primary cell cultures derived from the subfornical organ or organum vasculosum laminae terminalis of five- to six-day-old rat pups were used to measure alterations in intracellular calcium at the single cell level. Neurons and astrocytes were identified by immunocytochemical staining for specific marker proteins. Bath application of angiotensin II (10(-10)-10(-6) M) dose-dependently induced calcium transients in neurons (19.6%) and astrocytes (15.7%), and angiotensin II threshold concentrations to elicit intracellular calcium signalling proved to be one order of magnitude higher in astrocytes as compared to neurons (10(-9) M). At angiotensin II concentrations higher than 10(-7) M, pronounced desensitization of the angiotensin II receptor occurred. Employing the angiotensin II receptor antagonists losartan (DUP-753; AT1-receptor) and PD-123319 (AT2-receptor), exclusive expression of the AT1 receptor subtype coupled to intracellular calcium concentration signalling could be demonstrated for neurons and astrocytes. In all cells examined, the angiotensin II-evoked increase in intracellular calcium concentrations could be fully suppressed in the absence of extracellular calcium. Co-activation by angiotensin II and other agents (vasopressin, its fragment 8-arginine-vasopressin(4-9), oxytocin, endothelin) was indicated for subfornical organ neurons and organum vasculosum laminae terminalis astrocytes.
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PMID:Angiotensin II-induced calcium signalling in neurons and astrocytes of rat circumventricular organs. 962 48

Ejaculated mammalian spermatozoa must reside in the female genital tract for some time before gaining the ability to fertilize the egg. During this time, spermatozoa undergo some physiological changes that collectively are called capacitation. Capacitation of mammalian spermatozoa is a prerequisite for acrosome reaction, which is an exocytotic event occurring before fertilization. The specific biophysical and biochemical changes that accompany sperm capacitation and the agonists inducing acrosome reaction are not fully understood. Using SDS-gel electrophoresis and immunoblotting, we demonstrate the existence of a class of angiotensin receptors (AT1) in bovine spermatozoa. In capacitated sperm, we show that angiotensin II (ANG II) AT1 receptors are localized in the head and tail, whereas in noncapacitated cells the receptors are localized in the tail only. We find that ANG II markedly stimulates acrosomal exocytosis of capacitated bovine spermatozoa in vitro in a concentration range of 0.1-10 nM. No effect of ANG II was found in noncapacitated cells. The ability of ANG II to stimulate the acrosome reaction depends on the presence of calcium ions in the incubation medium. The ANG II-induced acrosome reaction was markedly inhibited by a selective AT1 receptor antagonist, losartan (DUP 753). PD-123319, a selective antagonist of the ANG II AT2 receptor, had no effect on the ANG II-induced acrosome reaction. Thus ANG II via activation of AT1 receptors may play a regulatory role in the induction of the acrosome reaction.
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PMID:Angiotensin II induces acrosomal exocytosis in bovine spermatozoa. 968 78

Peptide delivery toward its targets in an intact organ is equally as important as its routing from the systemic circulation to cell surface receptor sites. A physical model pertinent to a heart perfusion technique in Sprague-Dawley rats is presented describing reversible binding of angiotensin II and/or antagonist (DUP 753, losartan) with the microvascular endothelial receptor subtypes as well as with the cardiac myocyte receptor subtypes that are exposed to the perfusate by CHAPS-treatment. Analysis of the collected effluents are curve-fitted with a conservation equation and a first-order Bessel function. The results suggest that angiotensin II delivery and binding to the pool of receptor subtypes both at the level of the microvascular endothelium and cardiac myocyte sites differ marginally in binding affinities. The findings postulate that angiotensin II can have access to the myocyte site in an intact heart by an endothelial angiotensin II-receptor-internalization process. In addition, considering that the AT1- and AT2-receptor subtypes are present in equal proportions and have equal binding affinities with angiotensin II, the results of the 3H-DUP 753 binding indicated approximately 3-3.5 times higher affinity to the AT1-receptors subtype than angiotensin II at both the endothelial and myocyte sites. In the presence of losartan, angiotensin II binding showed higher affinity with the exposed unopposed AT2-receptor subtype than with the receptor pool, which could be due to alterations in the AT2-receptor structure and configuration. This increase in the binding affinity of angiotensin II with the AT2-receptor subtype may be categorized under the direct effect of the AT1-antagonist modality in producing cardioprotective effects.
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PMID:Angiotensin II delivery and binding at the microvascular endothelium and cardiac myocyte surfaces in perfused rat hearts. 981 91

Significant angiotensin (Ang) (1-7) production occurs in kidney and effects on renal function have been observed. The present study was undertaken to investigate binding characteristics of the heptapeptide to Ang II receptors present in rat renal cortex. [125I]-Ang II binding to rat glomeruli membranes was analyzed in the presence of increasing concentrations of Ang II, Ang-(1-7), DUP 753 and PD 123319. Linearity of the Scatchard plot of the [125I]-Ang II specific binding to rat glomeruli membranes indicated a single population of receptors, with a Kd value of 0.7 +/- 0.1 nM and a Bmax of 198 +/- 0.04 fmol/mg protein. DUP 753, an specific AT1 receptor antagonist, totally displaced the specific binding of [125I]-radiolabelled hormone with a Ki of 15.8 +/- 0.9 nM, while no changes were observed in the presence of the selective AT2 receptor antagonist, PD 123319. The specific [125I]-Ang II binding to rat glomerular membranes was displaced by Ang-(1-7) with high affinity (Ki = 8.0 +/- 3.2 nM). We conclude that radioligand binding assays in the presence of selective Ang II antagonists DUP 753 and PD 123319 suggest the unique presence of AT1, receptors in rat glomeruli and a possible role in the control of the biological renal effects of Ang-(1-7).
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PMID:Angiotensin-(1-7) binds at the type 1 angiotensin II receptors in rat renal cortex. 1053 8

We studied the effects of ANG II on extracellular signal-regulated kinase (ERK)1/2 phosphorylation in rat pituitary cells. ANG II increased ERK phosphorylation in a time- and concentration-dependent way. Maximum effect was obtained at 5 min at a concentration of 10-100 nM. The effect of 100 nM ANG II was blocked by the AT1 antagonist DUP-753, by the phospholipase C (PLC) inhibitor U-73122, and by the MAPK kinase (MEK) antagonist PD-98059. The ANG II-induced increase in phosphorylated (p)ERK was insensitive to pertussis toxin blockade and PKC depletion or inhibition. The effect was also abrogated by chelating intracellular calcium with BAPTA-AM or TMB-8 by depleting intracellular calcium stores with a 30-min pretreatment with EGTA and by pretreatment with herbimycin A and PP1, two c-Src tyrosine kinase inhibitors. It was attenuated by AG-1478, an inhibitor of epidermal growth factor receptor (EGFR) activation. Therefore, in the rat pituitary, the increase of pERK is a Gq- and PLC-dependent process, which involves an increase in intracellular calcium and activation of a c-Src tyrosine kinase, transactivation of the EGFR, and the activation of MEK. Finally, the response of ERK activation by ANG II is altered in hyperplastic pituitary cells, in which calcium mobilization evoked by ANG II is also modified.
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PMID:Angiotensin II phosphorylation of extracellular signal-regulated kinases in rat anterior pituitary cells. 1275 18

Although pregnancy is clearly associated with refractoriness to infused angiotensin II (AII) in the uteroplacental unit, there is still dispute over the mechanism by which angiotensin type 1 and type 2 receptors (AT1R and AT2R) may mediate this response in the uterine artery. This is in large part due to incomplete knowledge of levels of AT1R and AT2R expression and function in uterine artery endothelium (UA Endo) in the nonpregnant (NP) and pregnant (P) states, combined with the disagreement on whether AII may act through release of adrenomedullary catecholamines. The authors have previously described an increase in AT1R in UA Endo but not UA vascular smooth muscle (VSM) during pregnancy as compared to the nonpregnant intact ewe. Herein they report that the pregnancy-associated increase in AT(1)R expression in UA Endo is regulated by ovarian steroids. Using a recently developed antibody to AT2R, the authors now show there is no change in AT2R in UA Endo or VSM associated with ovarian function, and although AT2R is not changed in UA Endo by pregnancy, there is a significant decrease observed in UA VSM at that time. The authors also examined changes in receptors in UA Endo and VSM in estrogen (E2beta)-primed ewes in view of the common use of this model as a control for physiologic studies. In contrast to their findings in nonprimed nonpregnant or pregnant animals, the authors observed a significant increase in both AT1R and AT2R in UA Endo in response to the supraphysiologic priming with E2beta. In order to address the possible functionality of AT1R or AT2R in UA Endo, the authors used the uterine artery endothelial cell (UAEC) model of UA endothelial cells maintained in culture to passage 4. Differences in expression of AT1R or AT2R were normalized at passage 4 in P-UAECs and NP-UAECs. Treatment with AII activated phospholipase C (PLC) in both NP- and P-UAECs but signaling through the extracellular signal-regulated kinase (ERK) pathway was dramatically enhanced in P-UAECs compared to NP-UAECs. Surprisingly, both phosphoinositol turnover and ERK2 phosphorylation responses failed to display the expected dose-responses. Inhibition of AII-stimulated ERK2 phosphorylation with antagonists DUP 753 (AT1R, 10 microM) and PD 123319 (AT2R, 10 microM) failed to selectively inhibit ERK2 phosphorylation. The authors conclude that (a) the net effect of pregnancy may be an increase in the AT1R/AT2R ratio in both UA Endo and VSM but through apparently distinct mechanisms, (b) the ovariectomized animal model is similar to the luteal state for AT1R and AT2R expression, while the E2beta-primed model does not resemble the nonpregnant or pregnant state, and (c) there is a real possibility that AII may mediate its effects either through a complex AT1R-AT2R interaction or via an as-yet unidentified non-AT1, non-AT2 receptor.
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PMID:Pregnancy and ovarian steroid regulation of angiotensin II type 1 and type 2 receptor expression in ovine uterine artery endothelium and vascular smooth muscle. 1603 15


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