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

Responses to angiotensin II, bradykinin and arginine vasopressin were compared in helical strips of canine pulmonary arteries and veins. Angiotensin II contracted the artery but relaxed the vein strip. The artery contraction was augmented by indomethacin and aspirin and was abolished by losartan. The vein relaxation was not affected by endothelium denudation but was abolished by the cyclooxygenase inhibitors, a prostaglandin I2 synthase inhibitor and losartan. The bradykinin-induced artery relaxation was inhibited by endothelium denudation, NG-nitro-L-arginine (L-NA) or indomethacin and abolished by their combined treatment. The vein relaxation produced by bradykinin was endothelium-independent and was abolished by indomethacin. Vasopressin produced a slight relaxation in the arteries, which was abolished by endothelium denudation and L-NA. The vein relaxation produced by vasopressin was abolished by endothelium denudation and combined treatment with L-NA and indomethacin. It may be concluded that (1) activation of angiotensin AT1 receptor subtype in smooth muscle produces contraction and also relaxation due to prostaglandin I2 release; the former predominates over the latter in the artery, whereas only the latter is operative in the vein, (2) the bradykinin-induced relaxation is due to nitric oxide (NO) from the endothelium and prostaglandin I2 from subendothelial tissues in the artery and solely to prostaglandin I2 in the veins, and (3) the vasopressin-induced relaxation is mediated by endothelial NO in the artery, and NO and prostaglandin I2 in the vein.
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PMID:Comparison of responses of canine pulmonary artery and vein to angiotensin II, bradykinin and vasopressin. 749 82

We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (> or = 10 nmol/l) this plateau phase was lower than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was associated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI2) release from the coronary vascular bed. The AII-induced changes in CPP, LVP, and PGI2 release were effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30 nmol/l), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/l). The adenosine A1 receptor antagonist 8-phenyltheophylline (0.1 mumol/l) attenuated the decline in CPP following the constriction phase without affecting the changes in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l) had no effect on the AII-induced changes in CPP, whereas the nitric oxide-synthase inhibitor NG-nitro-L-arginine (30 mumol/l) markedly potentiated the vasoconstriction but was without effect on the plateau phase of the response. In contrast to AII, the thromboxane analogue U46619 elicited sustained increases in CPP which were associated with slight decreases in LVP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart. 751 Aug 56

Angiotensin-(1-7) [Ang-(1-7)] was recently recognized to have novel biological functions that are distinct from those of Ang II. In these studies, we determined the vasoactive effects of Ang-(1-7) together with the endothelium-dependent mediator(s) of these responses in canine coronary arteries. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers perfused with 95% O2/5% CO2 at 37 degrees C. Ang-(1-7) caused significant concentration-dependent vascular relaxation (2.73 +/- 0.58 micromol/L, EC50) of rings precontracted with the thromboxane A2 analogue U46,619. Pretreatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (1 mol/L) abolished the vasodilator response to Ang-(1-7), whereas treatment with the cyclooxygenase inhibitor indomethacin (10 micromol/L) was without effect. The vasodilator response produced by Ang-(1-7) was blocked by 75% with the bradykinin B2 receptor antagonist Hoe 140 (1 micromol/L) or by 80% with the nonselective Ang II antagonist [Sar1,Thr8]-Ang II (1 micromol/L). In contrast, the selective AT1 or AT2 Ang II antagonists CV 11974 (1 micromol/L), and PD 123319 (1 micromol/L), respectively, were ineffective in inhibiting the Ang-(1-7)-elicited vasodilation. Furthermore, pretreatment of the coronary rings with 2 micromol/L Ang-(1-7) markedly potentiated the bradykinin response. These results suggest that Ang-(1-7) elicits coronary vasodilation that is specifically mediated by the endothelium-dependent release of nitric oxide. These responses involve a B2 bradykinin receptor and a non-AT1, non-AT2, angiotensin receptor. These data suggest that increases in circulating levels of Ang-(1-7) accompanying long-term administration of converting enzyme inhibitors or Ang II receptor blockers may contribute to the cardioprotective actions of these drugs.
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PMID:Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. 861 97

The present study was undertaken to determine whether trandolaprilat, an active form of angiotensin I converting enzyme (ACE) inhibitor, may improve ischemia/reperfusion-induced contractile dysfunction and metabolic derangement of isolated rat hearts. Ischemia (25 min) and subsequent 60-min reperfusion resulted in a small recovery of post-ischemic left ventricular developed pressure (LVDP), a sustained increase in left ventricular end-diastolic pressure, an increase in the release of creatine kinase and ATP metabolites from the perfused heart, and changes in myocardial sodium, potassium, calcium and magnesium contents. Treatment with 10-100 microM of trandolaprilat for the last 10 min of pre-ischemia recovered approximately 50-90% of pre-ischemic LVDP during reperfusion, whereas that with 30-100 microM of enalaprilat restored approximately 55-65% of the pre-ischemic LVDP. Treatment with either trandolaprilat or enalaprilat at these concentrations attenuated the release of creatine kinase and ATP metabolites into the perfusate during reperfusion. Treatment with 30 microM trandolaprilat suppressed ischemia/reperfusion-induced changes in myocardial ion content. Treatment with bradykinin during the last 10 min of pre-ischemia also resulted in a post-ischemic contractile recovery with a degree similar to that of the trandolaprilat-treated hearts. E4177, an AT1-antagonist, showed no effect on ischemia/reperfusion-induced changes in cardiac parameters. The enhancement of post-ischemic contractile recovery by the ACE inhibitor was abolished by treatment with either Hoechst 140, a bradykinin (BK2) antagonist, or diclofenac, a cyclooxygenase inhibitor. These results suggest that trandolaprilat is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts and altered BK metabolism is, at least in part, involved in this effect.
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PMID:Beneficial effects of angiotensin I converting enzyme inhibitor on post-ischemic contractile function of perfused rat heart. 887 76

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

This study was designed to define more precisely the relationship between specific angiotensin receptors and the growth of vascular smooth muscle cells in response to angiotensin II. These experiments employed quiescent A10 cells which were characterized as smooth muscle by the expression of specific contractlle proteins. Cell growth was monitored by measuring the incorporation of metabolic precursors into RNA or DNA. The treatment of A10 cells with angiotensin II (1 microM) stimulated a hypertrophic response as indicated by an increase in RNA synthesis and protooncogene expression in the absence of DNA synthesis. This increase in RNA synthesis could be blocked by PD123319, an AT2 antagonist, but not by losartan, an AT1 antagonist. RT-PCR analysis demonstrated that quiescent A10 cells express only the AT2 receptor while proliferating A10 cells express the AT1a and AT1b receptors in addition to the AT2 receptor. In addition, induction of AT2 receptor-mediated RNA synthesis was prevented by indomethacin, a cyclooxygenase inhibitor. These studies therefore support a direct connection between the AT2 receptor and smooth muscle growth that is mediated, in part, by prostaglandin synthesis.
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PMID:The angiotensin type 2 receptor mediates RNA synthesis in A10 vascular smooth muscle cells. 901 33

Elevated levels of angiotensin (Ang II) and its degradation products angiotensin III (Ang III) and angiotensin IV (Ang IV) may contribute to the regulation of vascular tone under various clinical circumstances. We investigated the contractile effects of Ang III and Ang IV in endothelium-denuded human saphenous vein (SV) preparations and compared them with those of Ang II. The veins were suspended in organ chambers, and changes in isometric force were recorded. Ang II (0.1-100 nM), Ang III (1 nM-3 microM), and Ang IV (0.3 microM-0.1 mM) caused concentration-dependent contractions with comparable maximal responses (Emax). Ang III was 16 times less active than Ang II, whereas Ang IV was approximately 2,700-fold less potent than Ang II. In the presence of the aminopeptidase-A and -M inhibitor amastatin (10 microM), the potencies of Ang III and Ang IV were increased by approximately 16 and 12 times, respectively, although no changes of Ang II potency were observed. The AT1-selective Ang II receptor antagonist losartan (10 and 100 nM) but not the AT2-selective antagonist PD123177 (1 microM), shifted the concentration-response curves (CRC) for the angiotensin peptides to the right in a parallel manner. Preincubation with indomethacin (10 microM), a cyclooxygenase inhibitor, did not influence the CRCs for any of the angiotensin peptides studied. Tachyphylaxis was investigated by constructing a second series of CRCs for the angiotensin peptides after an interval of 60 min. Ang II showed strong tachyphylaxis (the Emax value of the second Ang II CRC was approximately 50% of the first), whereas Ang III and Ang IV did not. Our results indicate that in endothelium-denuded human SV, both Ang III and Ang IV are less potent but similarly efficacious vasoconstrictor agents compared with Ang II. Endogenous aminopeptidase activity may counteract the effects of the angiotensin peptides. The contractile responses to all three peptides are mediated via AT1-receptors but not AT2-receptors.
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PMID:Comparative vasoconstrictor effects of angiotensin II, III, and IV in human isolated saphenous vein. 915 53

The aim of the present study was to commence a characterisation of some of the basic pharmacological properties of venom from the soldierfish (Gymnapistes marmoratus). Soldierfish venom was prepared by extraction into 10% glycerol and centrifugation to remove insoluble material. Protein content was determined and venom concentrations were expressed as microgram venom protein. Soldierfish venom (0.5-15 micrograms/ml) produced concentration-dependent contractile responses in guinea-pig isolated ileum (GPI) and longitudinal smooth muscle (LSM) preparations. The muscarinic receptor antagonist atropine (10 nM) significantly inhibited responses of LSM to soldierfish venom (2.5 micrograms/ml). Responses to soldierfish venom (4-5 micrograms/ml) in GPI were not significantly affected by the ganglion-blocking drug mecamylamine (10 microM) or by incubation with blood cholinesterase. The cyclooxygenase inhibitor indomethacin (2 microM) significantly inhibited responses to soldierfish venom (2.5 micrograms/ml) in LSM. Neither the thromboxane A2/prostaglandin H2 receptor antagonist GR32191B (1 microM) nor the leukotriene receptor antagonist SB205312 (10 nM) significantly affected responses to soldierfish venom (5 micrograms/ml) in GPI. Responses to soldierfish venom (2.5-5 micrograms/ml) were not significantly inhibited by the histamine receptor antagonist mepyramine (0.5 microM), the angiotensin-converting enzyme inhibitor captopril (2 microM) or the neurokinin-1 receptor antagonist CP-99,994 (0.1 microM) in LSM. The angiotensin AT1 receptor antagonist EXP3174 (0.1 microM) also failed to inhibit significantly the responses to soldierfish venom (5 micrograms/ml) in GPI. A fluorometric assay for the detection of 5-hydroxytryptamine (5-HT) and related compounds indicated a level in soldierfish venom of 1.60 +/- 0.01 ng of 5-HT-like substance per microgram venom protein. Soldierfish venom (0.5-10 micrograms/ml) produced concentration-dependent contractile responses in rat isolated stomach fundus strips, and these responses (2.5 micrograms/ml) were significantly inhibited by the 5-HT1/5-HT2 receptor antagonist methysergide (0.1 microM). These results suggest that soldierfish venom may stimulate the release of acetylcholine to act at muscarinic receptors on guinea-pig gastrointestinal smooth muscle. The venom also appears to be causing the release of cyclooxygenase products, such as prostaglandins, and contains 5-HT, or a 5-HT-like substance, that acts directly at 5-HT receptors.
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PMID:An in vitro pharmacological examination of venom from the soldierfish Gymnapistes marmoratus. 924 8

Angiotensin II (ANG II) has long been known for its pressor and growth-promoting effects, which are both mediated by the AT1 receptor. By contrast, the AT2 receptor has recently been reported to mediate inhibition of proliferation through as yet undefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks the cells in G1 phase. Consistent with this, ANG II inhibits cyclin D1 expression and cyclin D1-associated kinase activity. The antimitogenic effect of ANG II is partly mimicked by the AT2-selective agonist CGP-42112. It is also blocked partly and in an additive fashion by the AT1- and AT2-selective antagonists losartan and PD-123319, indicating the contribution of both receptor subtypes to this response. AT1-dependent antiproliferation is selectively blocked by the cyclooxygenase inhibitor indomethacin and restored by prostaglandin E2, whereas AT2-receptor-mediated inhibition of growth is suppressed by the tyrosine phosphatase inhibitors orthovanadate and bpV(pic). Both pathways are, however, pertussis toxin sensitive. We hypothesize that, in fasciculata cells, the AT1 receptor inhibits bFGF-induced proliferation by stimulating prostaglandin synthesis, whereas the AT2 receptor mediates its effect through a pathway that requires protein tyrosine phosphatase activation.
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PMID:ANG II AT1 and AT2 receptors both inhibit bFGF-induced proliferation of bovine adrenocortical cells. 935 77

Stimulated release of vasodilator prostaglandins and nitric oxide by angiotensin II may counteract the vasoconstrictor effects of this octapeptide. We investigated the effects of inhibition of prostaglandin synthesis by indomethacin and of nitric oxide formation by NG-monomethyl-L-arginine (L-NMMA) on baseline forearm blood flow (FBF) and on angiotensin II-induced vasoconstriction in healthy subjects. For comparison, the effects of the AT1-receptor antagonist losartan on these parameters were determined. FBF was measured by venous occlusion plethysmography. Angiotensin II (0.01-10 ng/kg/min) was infused into the brachial artery, in the absence and presence of indomethacin (0.65 micrograms/kg/min; n = 8), L-NMMA (30 micrograms/kg/min; n = 5), and losartan (3 micrograms/kg/min; n = 12), respectively. Sodium nitroprusside was used to submaximally predilate the forearm vascular system. Baseline FBF remained unchanged with indomethacin and losartan, but was significantly decreased by -42 +/- 6% (mean +/- SEM) by L-NMMA. The dose-dependent angiotensin II-induced vasoconstriction was unaffected by indomethacin and L-NMMA, but was inhibited by losartan. Emax was -78 +/- 2% during control conditions, -84 +/- 3% during indomethacin (n.s.), -74 +/- 4% during L-NMMA (n.s.), and -17 +/- 6% during losartan infusion (p < 0.05). None of the interventions significantly changed the EC50 value of angiotensin II of -9.4 +/- 0.14 log M. In conclusion, in the human forearm of healthy subjects, neither endogenous angiotensin II nor cyclooxygenase-dependent prostaglandin synthesis plays a role in the genesis of vascular tone, whereas endogenous nitric oxide production does. The constrictor effects of angiotensin II are counteracted by neither stimulated release of prostaglandins nor by that of nitric oxide.
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PMID:Influence of indomethacin and L-NMMA on vascular tone and angiotensin II-induced vasoconstriction in the human forearm. 935 98


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