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

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

We have proposed that ischemic preconditioning in the rabbit heart is initiated by adenosine A1 receptor stimulation which results in an upregulation of protein kinase C (PKC). Subsequent sustained ischemia then causes renewed stimulation of adenosine A1 receptors with rapid reactivation of PKC and phosphorylation of a target protein(s) which mediates the protection. If the above theory is correct then angiotensin II (AII) receptor stimulation, which is known to activate PKC, should also protect the heart. Isolated rabbit hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium staining. Pretreating hearts with 100 mM AII for 5 min, followed by 10 min of drug-free perfusion prior to the prolonged ischemia limited infarction (7.2 +/- 2.0% of the risk area v 31.1 +/- 3.4% in control animals, P < 0.01). This protection could be blocked by the AT1 receptor blocker losartan (10 microM), but not by the AT2 receptor blocker PD 123319 (10 microM). Polymyxin B (50 microM), a PKC inhibitor, also blocked the protective effect of AII. These observations demonstrated that activation of PKC by AT1 receptor stimulation prior to ischemia does mimic ischemic preconditioning. Following AII infusion, administration, during the 30 min ischemic period, of either SPT [8-(p-sulfophenyl)theophylline] (an adenosine receptor blocker) or losartan failed to block AII's protective effect. However, co-administration of SPT and losartan did abort AII's protection suggesting that AII may not be completely washed out during the 10 min drug-free perfusion allowing residual agonist to reactivate PKC during the 30 min ischemia even when adenosine receptors are blocked. Thus, if only one of the receptors (AT1 or adenosine) were activated during the ischemic period, protection would occur. We conclude that activation of PKC by AII, prior to ischemia, can limit myocardial infarction. While PKC must be reactivated during ischemia to realize protection, the specific receptor type initiating reactivation is not crucial.
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PMID:Pretreatment with angiotensin II activates protein kinase C and limits myocardial infarction in isolated rabbit hearts. 760 6

We examined the renal effects of a specific adenosine A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 micrograms.kg-1.min-1 iv). Since adenosine is a potent inhibitor of renin release, additional experiments were performed with an angiotensin AT1-receptor antagonist (losartan, 10 mg/kg i.v.). DP CPX alone induced a significant (P < 0.05) decrease in afferent arteriolar resistance (RA, 1.83 +/- 0.18 to 1.43 +/- 0.06 dyn.s.cm-5 x 10(10); P < 0.05). This led to a rise in the transcapillary hydraulic pressure difference (delta P, 35 +/- 1 to 43 +/- 2 mmHg; P < 0.05). Surprisingly, the glomerular capillary ultrafiltration coefficient (Kf) fell (0.101 +/- 0.017 to 0.064 +/- 0.009 nl.s-1.mmHg-1, P < 0.05). Additionally, DPCPX infusion resulted in dramatic increases in both urine flow and sodium excretion. With losartan pretreatment, DPCPX did not cause significant changes in RA and delta P. Also, DPCPX increased Kf (0.057 +/- 0.005 to 0.075 +/- 0.008 nl.s-1.mmHg-1, P < 0.05). Furthermore, the large DPCPX-induced increases in urine flow and sodium excretion were largely suppressed by pretreatment with losartan. These data indicate that endogenous adenosine plays a significant role in maintaining afferent arteriolar tone and that the renin-angiotensin system may mediate some of the wide ranging renal effects of adenosine.
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PMID:Effects of selective A1 receptor blockade on glomerular hemodynamics: involvement of renin-angiotensin system. 797 81

The purpose of the present investigation was to examine the effects of KW-3902 [8-(noradamantan-3-yl)-1,3-dipropyl-xanthine], a selective and potent adenosine A1 receptor antagonist, in order to clarify the role of adenosine in the control of renal hemodynamics and urine formation in anesthetized dogs. KW-3902 was directly infused into the renal artery to eliminate the systemic effects of the drug. KW-3902 (10 micrograms/kg/min) almost completely inhibited the renal vasoconstriction induced by adenosine via A1 receptors. Intrarenal infusion of KW-3902 did not affect mean arterial pressure, renal blood flow, creatinine clearance, or arterial plasma renin activity, but drastically increased urine flow, urinary excretion of sodium, and osmolar clearance. Inhibition of the renin-angiotensin system using CV-11974 [2-ethoxy-1-((2'-(1-H-tetrazole-5-yl)biphenyl-4-yl) methyl)-1-H-benzimidazole-7-carboxylic acid], a selective AT1 antagonist, did not affect the diuretic action of KW-3902. These data suggest that endogenous adenosine does not play a significant role in the control of renal hemodynamics in whole kidney, but that it plays an important role in preserving body fluid via the A1 receptor independent of the renin-angiotensin system in anesthetized dogs.
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PMID:Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs. 939 79

To determine whether intrinsic angiotensin II (ANG II) type 1 receptor (AT1-R) stimulation modulates recovery of postischemic mechanical function, we studied the effects of selective AT1-R blockade with losartan on proton production from glucose metabolism and recovery of function in isolated working rat hearts perfused with Krebs-Henseleit buffer containing palmitate, glucose, and insulin. Aerobic perfusion (50 min) was followed by global, no-flow ischemia (30 min) and reperfusion (30 min) in the presence (n = 10) or absence (n = 14) of losartan (1 mumol/l) or the cardioprotective adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA, 0.5 mumol/l, n = 11). During reperfusion in untreated hearts (controls), left ventricular (LV) minute work partially recovered to 38% of aerobic baseline, whereas proton production increased to 155%. Compared with controls, CHA improved recovery of LV work to 79% and reduced proton production to 44%. Losartan depressed recovery of LV work to 0% without altering proton production. However, exogenous ANG II (1-100 nmol/l) in combination with losartan restored recovery of LV work during reperfusion in a concentration-dependent manner, suggesting that postischemic recovery of function depends on intrinsic AT1-R stimulation.
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PMID:Intrinsic ANG II type 1 receptor stimulation contributes to recovery of postischemic mechanical function. 961 59

The effects of adenosinergic and angiotensin IIergic agents and of their combinations on the seizure threshold in mice were determined by measuring the dose of timed-intravenous (tail vein) infused pentylenetetrazol (PTZ) required to elicit clonic seizures. All drugs were administered intracerebroventricularly (i.c.v.). Angiotensin II (ANG II), its peptide analogue sarmesin, the selective adenosine A1 receptor agonists N6-cyclopentyladenosine (CPA) and 2-chloroadenosine (2-ClAdo) significantly increased the PTZ seizure threshold. The selective AT1 receptor antagonist losartan blocked the anticonvulsant effect of ANG II, sarmesin and CPA. The selective AT2 receptor antagonist PD 123319 failed to block the effect of ANG II and sarmesin on the PTZ seizure threshold but reversed the threshold-increasing effect of CPA. The selective adenosine A1 receptor antagonist 8-(p-sulfophenyl)-theophylline (8-p-SPT) alleviated the threshold-increasing effect of CPA and ANG II. Concurrent injection of 2-ClAdo and ANG II as well as of 2-ClAdo and sarmesin, at doses which had no significant effect on the PTZ seizure threshold when given alone, acted synergistically, producing greater effect on the threshold. Taken together, the findings support the possibility of specific ANG II-adenosine A1 receptor interactions in the regulation of the PTZ seizure threshold.
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PMID:Adenosine-angiotensin II interactions in pentylenetetrazol seizure threshold in mice. 1039 74

The effects of adenosine A1 and A2A receptor agonists and antagonists administered intraperitoneally (i.p.) and their interaction with angiotensin II (Ang II) administered intracerebroventricularly (i.c.v.) were studied in mice using the acetic acid-induced abdominal constriction test. Ang II (0.1 microg/mouse) induced antinociception in this model. The adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.05, 0.25 and 0.5 mg/kg) also showed a well-developed antinociceptive effect. Ang II (0.1 microg/mouse) administered 5 min before CPA (0.25 mg/kg) decreased the number of writhes, i.e., it enhanced the antinociceptive effect of CPA. Losartan, an AT1 receptor antagonist (25 microg/mouse i.c.v.), enhanced the antinociceptive effect of CPA, while the AT2 receptor antagonist 1-[-4-(dimethylamino)-3-methylphenylmethyl]-5-diphenylacetyl)-4,5,6,7-tetrahydro 1H-4-imidazol [4,5c]pyridine-6 carboxylic acid, ditrifluoroacetate, dihydrate (PD 123319; 10 microg/mouse) had less effect. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 mg/kg), an adenosine A1 receptor antagonist, exhibited a pronociceptive effect and did not change the antinociceptive effect of Ang II. The adenosine A2A receptor agonist PD-125944 (DPMA; 0.1, 0.5 and 1 mg/kg) showed pronounced antinociceptive effect. Ang II (0.1 microg/mouse) did not significantly influence the antinociceptive effect of DPMA (0.1 mg/kg). The A2A receptor antagonist 3,7-dimethyl-1-propargilxanthine (DMPX; 0.1 mg/kg) had no effect on the number of writhes and did not influence the effect of Ang II. These data indicate that the antinociceptive effect of Ang II interacts with that produced by adenosine A1 receptor agonist.
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PMID:Interaction of angiotensin II and adenosine A1 and A2A receptor ligands on the writhing test in mice. 1190 Jul 65

Tubuloglomerular feedback (TGF) describes a causal and direct relationship between tubular NaCl concentration at the end of the ascending limb of the loop of Henle and afferent arteriolar tone. The use of genetically altered mice has led to an expansion of our understanding of the mechanisms underlying the functional coupling of epithelial, mesangial, and vascular cells in TGF. Studies in mice with deletions of the A or B isoform of NKCC2 (Na,K,2Cl cotransporter) and of ROMK indicate that NaCl uptake is required for response initiation. A role for transcellular salt transport is suggested by the inhibitory effect of ouabain in mutant mice with an ouabain-sensitive alpha1 Na,K-ATPase. No effect on TGF was observed in NHE2- and H/K-ATPase-deficient mice. TGF responses are abolished in A1 adenosine receptor-deficient mice, and studies in mice with null mutations in NTPDase1 or ecto-5'-nucleotidase indicate that adenosine involved in TGF is mainly derived from dephosphorylation of released ATP. Angiotensin II is a required cofactor for the elicitation of TGF responses, as AT1 receptor or angiotensin-converting enzyme deficiencies reduce TGF responses, mostly by reducing adenosine effectiveness. Overall, the evidence from these studies in genetically altered mice indicates that transcellular NaCl transport induces the generation of adenosine that, in conjunction with angiotensin II, elicits afferent arteriolar constriction.
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PMID:Tubuloglomerular feedback: mechanistic insights from gene-manipulated mice. 1841 52

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na(+) handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT1 receptor antagonist candesartan, the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination. Compared with controls, the baseline blood pressure, RBF, and renal vascular resistance (RVR) were similar in diabetics, whereas the glomerular filtration rate (GFR) and filtration fraction (FF) were increased. Candesartan, DPCPX, or the combination increased RBF and decreased RVR similarly in all groups. In controls, the GFR was increased by DPCPX, but in diabetics, it was decreased by candesartan. The FF was decreased by candesartan and DPCPX, independently. DPCPX caused the most pronounced increase in fractional Na(+) excretion in both controls and diabetics, whereas candesartan or the combination only affected fractional Li(+) excretion in diabetics. These results suggest that RBF, via a unifying mechanism, and tubular function are under strict tonic control of both ANG II and adenosine in both control and diabetic kidneys. Furthermore, increased vascular AT1 receptor activity is a contribution to diabetes-induced hyperfiltration independent of any effect of adenosine A1 receptors.
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PMID:Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors. 2328 98