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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Angiotensin II produced concentration-dependent enhancement of both stimulation-induced (S-I) efflux of [3H]-noradrenaline and stimulation-evoked vasoconstrictor responses in isolated preparations of rat caudal artery in which the noradrenergic transmitter stores had been labelled with [3H]-noradrenaline. The threshold concentrations of angiotensin II for enhancement of S-I efflux (between 0.03 and 0.1 microM) and of the stimulation-evoked vasoconstrictor responses (about 0.3 microM) were 10-1000 times higher than those that have been found for several other vascular preparations. 2. The AT1 angiotensin II receptor antagonist losartan (0.01 and 0.1 microM), reduced or abolished the enhancement of S-I efflux by 1 and 3 microM angiotensin II and the enhancement of vasoconstrictor responses by 1 microM angiotensin II. Surprisingly, the combination of 0.01 microM losartan and 0.1 microM angiotensin II enhanced S-I efflux to a much greater extent than did 0.1 microM angiotensin II alone. Moreover, the combination of 0.01 microM losartan and 0.1 microM angiotensin II enhanced stimulation-evoked vasoconstrictor responses, in contrast to the lack of effect of 0.1 microM angiotensin II alone. 3. In a concentration of 0.01 microM, the angiotensin II AT2 receptor antagonist PD 123319 did not affect the enhancement of either S-I efflux or vasoconstrictor responses by angiotensin II. However, in a higher concentration (0.1 microM), PD 123319 antagonized the enhancement of both the S-I efflux and vasoconstrictor responses by angiotensin II. 4. In concentrations of 0.01 and 0.1 microM, PD 123319 prevented the marked enhancement of both S-I efflux and stimulation-evoked vasoconstrictor responses produced by the combination of 0.1 microM angiotensin II and 0.01 microM losartan. 5. The potentiation by losartan (0.01 microM) of the facilitatory effect of 0.1 microM angiotensin II on S-I efflux and on stimulation-evoked vasoconstriction was still observed in the presence of either the cyclooxygenase inhibitor indomethacin (3 microM), or the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). 6. The findings confirm our previous suggestion that, in the rat caudal artery, angiotensin II receptors similar to the AT1B subtype subserve enhancement of transmitter noradrenaline release. 7. The synergistic prejunctional interaction of 0.01 microM losartan and 0.1 microM angiotensin II may be due to either the unmasking by losartan of a latent population of angiotensin II receptors also subserving facilitation of transmitter noradrenaline release, or alternatively, losartan may block an inhibitory action of angiotensin II on transmitter noradrenaline release which normally opposes its facilitatory effect.
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PMID:Multiple prejunctional actions of angiotensin II on noradrenergic transmission in the caudal artery of the rat. 892 48

The angiotensin AT2 receptor modulates renal production of cyclic guanosine 3',5'-monophosphate (cGMP; J. Clin. Invest. 1996. 97:1978-1982). In the present study, we hypothesized that angiotensin II (Ang II) acts at the AT2 receptor to stimulate renal production of nitric oxide leading to the previously observed increase in cGMP. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) cGMP in response to intravenous infusion of the AT2 receptor antagonist PD 123319 (PD), the AT1 receptor antagonist Losartan, the nitric oxide synthase (NOS) inhibitor nitro--arginine-methyl-ester (-NAME), the specific neural NOS inhibitor 7-nitroindazole (7-NI), or Ang II individually or combined in conscious rats during low or normal sodium balance. Sodium depletion significantly increased RIF cGMP. During sodium depletion, both PD and -NAME caused a similar decrease in RIF cGMP. Combined administration of PD and -NAME decreased RIF cGMP to levels observed with PD or -NAME alone or during normal sodium intake. During normal sodium intake, Ang II caused a twofold increase in RIF cGMP. Neither PD nor -NAME, individually or combined, changed RIF cGMP. Combined administration of Ang II and either PD or -NAME produced a significant decrease in RIF cGMP compared with that induced by Ang II alone. Combined administration of Ang II, PD, and -NAME blocked the increase in RIF cGMP produced by Ang II alone. During sodium depletion, 7-NI decreased RIF cGMP, but the reduction of cGMP in response to PD alone or PD combined with 7-NI was greater than with 7-NI alone. During normal sodium intake, 7-NI blocked the Ang II-induced increase in RIF cGMP. PD alone or combined with 7-NI produced a greater inhibition of cGMP than did 7-NI alone. During sodium depletion, 7-NI (partially) and -NAME (completely) inhibited RIF cGMP responses to -arginine. These data demonstrate that activation of the renin- angiotensin system during sodium depletion increases renal nitric oxide production through stimulation by Ang II at the angiotensin AT2 receptor. This response is partially mediated by neural NOS, but other NOS isoforms also contribute to nitric oxide production by this pathway.
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PMID:The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. 921 2

In the present study we tested the hypothesis whether an angiotensin AT2 receptor-mediated stimulation of the bradykinin (BK)/nitric oxide (NO) system can account for the effects of AT1 receptor antagonism on aortic cGMP described previously in SHRSP. Adult SHRSP were treated for 4 hours with angiotensin II (ANG II) (30 ng/kg per min IV) or vehicle (0.9% NaCl I.V.). Animals were pretreated with vehicle, losartan (100 mg/kg P.O.), PD 123319 (30 mg/kg I.V.), losartan plus PD 123319, icatibant (500 microg/kg I.V.), N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg I.V.), or minoxidil (3 mg/kg I.V.). Mean arterial blood pressure (MAP) was continuously monitored over the 4-hour experimental period, and plasma ANG II and aortic cGMP were measured by RIA at the end of the study. ANG II infusion over 4 hours raised MAP by about 20 mm Hg. Losartan alone or losartan plus ANG II as well as minoxidil plus ANG II markedly reduced blood pressure when compared to vehicle-treated or ANG II-treated animals, respectively. Plasma levels of ANG II were increased 2-fold by ANG II infusion alone or by ANG II in combination with icatibant, L-NAME, or minoxidil. The increase in plasma ANG II levels was even more pronounced after losartan treatment. Aortic cGMP content was significantly increased by ANG II, losartan, losartan plus ANG II, and minoxidil plus ANG II by 60%, 45%, 68%, and 52%, respectively (P<.05). The effects of ANG II and of losartan plus ANG II on aortic cGMP content were both blocked by cotreatment with the AT2 receptor antagonist PD 123319. Icatibant and L-NAME abolished the effects of ANG II on aortic cGMP. Our results demonstrate the following: (1) ANG II increases aortic cGMP by an AT2 receptor-mediated action because the effect could be prevented by an AT2 receptor antagonist; (2) the effect of ANG II was not secondary to blood pressure increase because it remained under reduction of MAP with minoxidil; (3) losartan increased aortic cGMP most likely by increasing plasma ANG II levels with a subsequent stimulation of AT2 receptors; and (4) the effects of AT2 receptor stimulation are mediated by BK and, subsequently, NO because they were abolished by B2 receptor blockade as well as by NO synthase inhibition.
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PMID:AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. 945 27

Footshocks increased mean arterial pressure and heart rate. Systemic administration of losartan, a specific angiotensin AT(1) receptor antagonist, not only inhibited the pressor response to footshocks, but also resulted in vasodepression. Administration of 1-[[4-(dimethylamino)3-methylphenyl]methyl]-5 (diphenylacetyl)-4,5,6, 7-tetrahydro-1H imidazol (4,5-c] pyridine-6-carboxilic acid, ditrifluoro acetatemonohydrate (PD 123319), a specific angiotensin AT(2) receptor antagonist, did not alter the hemodynamic response to footshocks. Simultaneous blockade of angiotensin AT(1) and AT(2) receptors by combined administration of losartan and PD 123319, eliminated the vasodepressor response to footshocks unmasked in losartan-pretreated rats. Saralasin, a non-specific angiotensin receptor antagonist, abolished the cardiovascular response to footshocks similarly like the losartan+PD 123319 treatment. Our data suggest that the vasodepressor response to footshocks in the presence of an angiotensin AT(1) receptor antagonist is triggered by activation of angiotensin AT(2) receptors. We studied the role of kinins, nitric oxide and prostaglandins in the vasodepressor response observed after footshocks. The decrease in mean arterial pressure observed after footshocks in losartan-treated rats was blunted by icatibant (HOE 140), N(G)-nitro-L-arginine-methyl ester (L-NAME) or indomethacin, indicating that kinins, nitric oxide and prostaglandins appear to be involved in the pressure response to footshocks during angiotensin AT(1) receptor blockade.
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PMID:Angiotensin AT(2) receptors mediate vasodepressor response to footshock in rats. Role of kinins, nitric oxide and prostaglandins. 1077 Oct 41

The heptapeptide, angiotensin-(1-7), is an active member of the renin-angiotensin system. The present study was designed to characterize the role of endothelium in relaxations of large cerebral arteries to angiotensin-(1-7). Rings of canine middle cerebral arteries were suspended in organ chambers for isometric force recording. The levels of cyclic guanosine 3',5'-monophosphate (cGMP) were assessed by radioimmunoassay. During contraction to uridine 5'-triphosphate (UTP, 3x10(-6) to 10(-5) mol/l), angiotensin-(1-7) (10(-9) to 3x10(-5) mol/l) caused concentration-dependent relaxations in arteries with endothelium, but not in endothelium-denuded vessels. Angiotensin-(1-7) significantly increased formation of cGMP. Nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 3x10(-4) mol/l), and selective soluble guanylate cyclase inhibitor, 1 H-[1,2, 4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ, 3x10(-6) mol/l), abolished angiotensin-(1-7)-induced relaxations. Angiotensin receptor antagonists, losartan (10(-5) mol/l), PD 123319 (10(-5) mol/l), [Sar(1),Thr(8)]-angiotensin II (10(-5) mol/l) [Sar(1),Val(5), Ala(8)]-angiotensin II (10(-5) mol/l) or [7-D-Ala]-angiotensin 1-7 (10(-6) mol/l) did not affect these relaxations. However, angiotensin-converting enzyme inhibitor, captopril (10(-5) mol/l) augmented relaxations to angiotensin-(1-7). Finally, bradykinin B(2) receptor antagonist, [D-Arg(0),Hyp(3),Thi(5),D-Tic(7), Oic(8)]-bradykinin (HOE 140, 5x10(-8) mol/l) significantly reduced the effect of angiotensin-(1-7), while bradykinin B(1) receptor antagonist, des-Arg(9), [Leu(8)]-bradykinin (6x10(-9) mol/l) did not influence the vascular response to the heptapeptide. These findings indicate that (1) angiotensin-(1-7) produces relaxation of canine middle cerebral arteries by the release of nitric oxide from endothelial cells, (2) angiotensin receptors do not mediate endothelium-dependent relaxations to the heptapeptide, and (3) this effect appears to be dependent on activation of local production of kinins. Our studies support the concept that angiotensin-(1-7), as a natural vasodilator hormone, may counterbalance the hemodynamic actions of angiotensin II.
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PMID:Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery. 1091 12

The aim of the present work was to characterize the interaction between the adrenergic system and angiotensin II-stimulated nitric oxide (NO) release in rabbit aorta. Rings of thoracic aorta were placed in an isolated organ bath. Equilibration was performed during 30 min, and after washing, angiotensin II was added at different concentrations, during 20 min. In another group two stimulations were performed with an interval of 60 min. Angiotensin II antagonists: losartan, PD 123319 and Sar1-Leu8-angiotensin II, alpha 2 adrenergic antagonist: yohimbine, all at 10(-5) M and L-NAME or D-NAME 10(-2) M, were added before stimulation with angiotensin II 10(-6) M or 5.10(-6) M. In another group, besides losartan or PD 123319, yohimbine was added. Nitrite determination was performed with Griess reagent. Angiotensin II 10(-8) to 10(-6) M increased NO metabolite production measured as nitrites referred to the control. In higher concentrations there was a diminution in relation to 10(-6) M. Angiotensin II nitrite release fell in the second stimulation with the hormone in all cases, whereas it was blocked by L-NAME. It was increased by angiotensin II antagonist only at maximal concentrations of the hormone, an effect abolished by yohimbine. Likewise, yohimbine diminished nitrite production at concentrations of angiotensin II of 5.10(-6) but not at 10(-6) M. These results allow us to postulate that NO release induced by angiotensin II would be in part mediated by alpha 2 receptors. Angiotensin II antagonists unmask these effects at maximal concentrations of the hormone, whereas at supramaximal concentrations inhibitory mechanisms would prevail, which would be balanced by alpha 2 activation.
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PMID:[Effect of angiotensin II and alpha2 adrenergic receptor antagonists on angiotensin II-stimulated nitric oxide release]. 1156 72

1. The contribution of the local vascular production of angiotensin-(1-7) [Ang-(1-7)] to the control of alpha-adrenergic-induced contractions in the aorta of Sprague-Dawley (SD) and TGR(mRen-2)27 [mRen-2] rats was studied. 2. In mRen-2 rats, contractile responses to phenylephrine were diminished as compared to control SD rats in endothelium containing but not in endothelium-denuded vessels. L-NAME increased contractile responses to phenylephrine in mRen-2 rats and, after nitric oxide synthase blockade, responses to phenylephrine became comparable in both strains. 3. Inhibition of angiotensin-converting enzyme (ACE) by captopril potentiated contractile responses in mRen-2 rats and diminished contractile responses in SD rats, both effects being dependent on the presence of a functional endothelium. The effect of captopril in mRen-2 rats was abolished in vessels pre-incubated with Ang-(1-7). 4. Blockade of Ang-(1-7) and bradykinin (BK) receptors by A-779 and HOE 140 respectively, increased phenylephrine-induced contraction in mRen-2, but not in SD rats. This effect was seen only in endothelium-containing vessels. 5. Angiotensin II AT(1) and AT(2) receptor blockade by CV 11974 and PD 123319 did not affect the contractile responses to phenylephrine in aortas of transgenic animals but diminished the response in SD rats. This effect was only seen in the presence of a functional endothelium. 6. It is concluded that the decreased contractile responses to phenylephrine in aortas of mRen-2 rats was dependent on an intact endothelium, the local release and action of Ang-(1-7) and bradykinin.
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PMID:Angiotensin-(1-7) is involved in the endothelium-dependent modulation of phenylephrine-induced contraction in the aorta of mRen-2 transgenic rats. 1193 15

In the present study in normotensive Wistar Kyoto rats (WKY), we investigated whether any angiotensin II (ANG II) increases in vascular cyclic GMP production were via stimulation of AT(2) receptors. Adult WKY were infused for 4h with ANG II (30 ng/kg per min, i.v.) or vehicle (0.9% NaCl, i.v.) after pretreatment with (1) vehicle, (2) losartan (100 mg/kg p.o.), (3) PD 123319 (30 mg/kg i.v.), (4) losartan+PD 123319, (5) icatibant (500 microg/kg i.v.), (6) L-NAME (1 mg/kg i.v.), (7) minoxidil (3 mg/kg i.v.). Mean arterial blood pressure (MAP) was continuously monitored, and plasma ANG II and aortic cyclic GMP were measured at the end of the study. ANG II infusion over 4h raised MAP by a mean of 13 mmHg. This effect was completely prevented by AT(1) receptor blockade. PD 123319 slightly attenuated the pressor effect induced by ANG II alone (123.4+/-0.8 versus 130.6+/-0.6) but did not alter MAP in rats treated simultaneously with ANG II + losartan (113+/-0.6 versus 114.3+/-0.8). Plasma levels of ANG II were increased 2.2-3.7-fold by ANG II infusion alone or ANG II in combination with the various drugs. The increase in plasma ANG II levels was most pronounced after ANG II+losartan treatment but absent in rats treated with losartan alone. Aortic cyclic GMP levels were not significantly changed by either treatment. Our results demonstrate that the AT(2) receptor did not contribute to the cyclic GMP production in the vascular wall of normotensive WKY.
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PMID:Effect of angiotensin AT2 receptor stimulation on vascular cyclic GMP production in normotensive Wistar Kyoto rats. 1267 80

1. The mechanisms involved in the vasodilator actions of angiotensin II (Ang II) have not yet been completely elucidated. We investigated the potential mechanisms that seem to be involved in the Ang II vasodilator effect using rat isolated mesenteric vascular bed (MVB). 2. Under basal conditions, Ang II does not affect the perfusion pressure of MVB. However, in vessels precontracted with norepinephrine, Ang II induces vasodilation followed by vasoconstriction. Vasoconstrictor, but not the vasodilation of Ang II, is inhibited by AT(1) antagonist (losartan). The vasodilator effect of Ang II was not inhibited by AT(2), angiotensin IV and angiotensin 1-7 receptor antagonists alone (PD 123319, divalinal, A 779, respectively). 3. The vasodilator effect of Ang II is significantly reduced by endothelial removal (deoxycholic acid), but not by indomethacin. Inhibition of NO-synthase by N(G)-nitro-l-arginine methyl ester (l-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ) reduces the vasodilator effect of Ang II. This effect is also reduced by tetraethylammonium (TEA) or l-NAME, and a combination of l-NAME plus TEA increases the inhibitory effect of the antagonists alone. However, indomethacin does not change the residual vasodilator effect observed in vessels pretreated with l-NAME plus TEA. 4. In vessels precontracted with norepinephrine and depolarized with KCl 25 mm or treated with Ca(2+)-dependent K(+) channel blockers (charybdotoxin plus apamin), the effect of Ang II was significantly reduced. However, this effect is not affected by ATP and voltage-dependent K(+) channel blockers (glybenclamide and 4-aminopyridine). 5. Inhibition of kininase II with captopril significantly potentiates the vasodilator effect of bradykinin (BK) and Ang II in the rat MVB. The inhibitory effect of the B(2) receptor antagonist HOE 140 on the vasodilator effect of Ang II is further enhanced by PD 123319 and/or A 779. 6. The present findings suggest that BK plays an important role in the endothelium-dependent vasodilator effect of Ang II. Probably, the link between Ang II and BK release is modulated by receptors that bind PD 123319 and A 779.
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PMID:The role of bradykinin, AT2 and angiotensin 1-7 receptors in the EDRF-dependent vasodilator effect of angiotensin II on the isolated mesenteric vascular bed of the rat. 1475 4

We investigated the effects of injection into the supraoptic nucleus (SON) of losartanand PD 123319 (nonpeptide AT(1) and AT(2)-angiotensin II [ANG II] receptor antagonists, respectively); d(CH(2))(5)-Tyr(Me)-AVP (AVPA; an arginine-vasopressin [AVP] V(1) receptor antagonist), FK 409 (a nitric oxide [NO] donor), and N(W)-nitro-l-arginine methyl ester (l-NAME; an NO synthase inhibitor) on water intake, sodium chloride 3% (NaCl) intake and arterial blood pressure induced by injection of ANG II into the lateral septal area (LSA). Male Holtzman rats (250-300 g) were implanted with cannulae into SON and LSA unilaterally. The drugs were injected in 0.5 microl over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. ANG II was injected at a dose of 10 pmol. ANG II antagonists and AVPA were injected at doses of 80 nmol. FK 409 and l-NAME were injected at doses of 20 and 40 microg, respectively. Water and NaCl intake was measured over a 2-h period. Prior administration of losartan into the SON decreased water and NaCl intake induced by injection of ANG II. While there was a decrease in water intake, ANG II-induced NaCl intake was significantly increased following injection of AVPA. FK 409 injection decreased water intake and sodium intake induced by ANG II. l-NAME alone increased water and sodium intake and induced a pressor effect. l-NAME-potentiated water and sodium intake induced by ANG II. PD 123319 produced no changes in water or sodium intake induced by ANG II. The prior administration of losartan or AVPA decreased mean arterial pressure (MAP) induced by ANG II. PD 123319 decreased the pressor effect of ANG II to a lesser degree than losartan. FK 409 decreased the pressor effect of ANG II while l-NAME potentiated it. These results suggest that both ANG II AT(1) and AVP V(1) receptors and NO within the SON may be involved in water intake, NaCl intake and the pressor response were induced by activation of ANG II receptors within the LSA. These results do not support the involvement of LSA AT(2) receptors in the mediation of water and NaCl intake responses induced by ANG II, but influence the pressor response.
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PMID:Interaction between supraoptic nucleus and septal area in the control of water, sodium intake and arterial blood pressure induced by injection of angiotensin II. 1509 11


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