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

Renin-angiotensin (RA) system plays an important role in cardiovascular homeostasis. Here, we have described the recent progress in our study of renin release as well as the cellular action of angiotensin II. (1) Microdissection of an isolated afferent artery with or without macula densa (MD) has revealed that renin release is regulated by NaCl exposure to MD. Furosemide, prostaglandins (PGE2 and PGI2) and adenosine modulate its function. (2) Angiotensin (ang) II increases cytosolic free calcium and induces the formation of inositolphosphates in vascular smooth muscle cells. Deduced protein structure of ang II receptor (AT1-R) cDNA has indicated the presumed link of AT1-R with phospholipase C. Through the cellular action, ang II has been reported to regulate gene expression.
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PMID:[Mechanism of renin release and cellular action of angiotensin II]. 129 35

Angiotensin II (AII) can release arachidonic acid metabolites such as prostacyclin (PGI2) and PGE2 from cells in cultures. It has recently been reported that the AT1 selective nonpeptide AII receptor antagonist losartan had similar effects. The present study was undertaken to further evaluate the effects of AII and losartan on cells which synthesize prostaglandins, including vascular smooth muscle, endothelial, and glial cells. Inhibition of specific [125I]AII binding was demonstrated in porcine smooth muscle cell (PSMC) suspensions with unlabeled AII and losartan. The IC50 values were 1.3 x 10(-9) mol/L and 7.7 x 10(-9) mol/L, respectively. PD123177 (an AT2 selective antagonist) had no effect on binding. AII produced a concentration-related increase in calcium mobilization (fura-2 fluorescence) which was blocked by losartan (IC50 = 8.4 x 10(-8) mol/L) but not by PD123177 (10(-6) mol/L). AII (10(-7) to 10(-5) mol/L) stimulated the basal release of PGI2 by 100%. This response was blocked by losartan (10(-6) to 10(-5) mol/L) but not by PD123177 (10(-6) to 10(-5) mol/L) and neither agent stimulated basal release in PSMC. Similar effects of AII and antagonists were observed upon receptor binding and PGE2 release in primary rat astrocyte (RA) cultures. AII did not release PGI2 from porcine endothelial cells, bovine pulmonary arterial endothelial cells, or rat C6 glioma cells. Losartan had no significant effect at 10(-5) mol/L. By contrast, bradykinin or the calcium ionophore A23187 dramatically increased PGI2 release in each of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AT1 receptors mediate the release of prostaglandins in porcine smooth muscle cells and rat astrocytes. 141 54

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

Marked neointima formation occurs after balloon injury to the intima of rat arteries. Angiotensin II has been implicated as a growth factor in this process, since angiotensin converting enzyme (ACE) inhibitors block neointima formation after injury. However, ACE is an important kininase, and its inhibitors may act in part by a kinin-mediated mechanism. Kinins are also known to stimulate synthesis of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and prostacyclin, both of which have antigrowth effects. To determine whether the effect of ACE inhibitors on neointima formation is due to blockade of angiotensin II synthesis alone and/or inhibition of kinin inactivation, we followed two approaches. First, we compared the inhibition of neointima formation induced by the AT1-type angiotensin II receptor antagonist losartan with that caused by the ACE inhibitor ramipril. We also studied whether a kinin receptor antagonist, Hoe 140, blocks the effect of two different ACE inhibitors, ramipril and enalapril, on neointima formation. In addition, we studied whether the effect of ramipril is blocked by an NO synthesis inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME). Although both ramipril and losartan significantly reduced neointima formation, ramipril had a more marked effect (p < 0.05 for ramipril versus losartan). The kinin antagonist Hoe 140 reduced the inhibitory effect of ramipril and enalapril by 73% and 62%, respectively. The remaining effect of the ACE inhibitors was now similar to that of losartan. Inhibition of neointima formation by ramipril was also blocked by the NO synthesis inhibitor L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation. 768 31

The objective of this study was to evaluate the mechanisms of the renin secretion response to the angiotensin II (AII) receptor type 1 (AT1) antagonist losartan (DuP 753) in anesthetized rabbits. All receptor blockade with losartan (4 mg/kg bolus and 2 mg/kg/hr i.v.) decreased blood pressure (BP) and increased plasma renin activity (PRA) and heart rate (HR) significantly, whereas the beta-1 adrenoceptor antagonist atenolol (0.02 mg/kg/min i.v.) caused significant reductions in these parameters. Atenolol blocked HR and PRA responses but not the effect of losartan on BP. Cyclooxygenase inhibition with indomethacin (5 mg/kg bolus and 40 micrograms/kg/min i.v.) did not result in significant effects, and the coadministration of indomethacin and losartan resulted in a greater PRA effect than with losartan alone. These results preclude the involvement of prostaglandins, such as PGE2 and PGI2, in the renin response to losartan. The PRA response to atenolol alone suggests that renin release in anesthetized rabbits is under tonic control by beta adrenergic receptors. Furthermore, the discrepancy in the PRA responses to equipotent hypotensive doses of hydralazine and losartan indicates that beta adrenoceptor activation in the kidney, probably the result of blockade of AII-mediated inhibition of renin secretion, contributes to the renin-releasing effect of the AT1 receptor antagonist losartan.
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PMID:Beta adrenoceptor blockade in rabbit inhibits the renin-releasing effect of AT1 receptor antagonist losartan. 790 89

Prostacyclin (PGI2), the major metabolite of arachidonic acid in adipose tissue, has been shown to play a key role in the process of preadipose cell differentiation in vitro. Moreover, angiotensin-II (Ang II) is able to induce the production of PGI2 in suspensions of isolated adipocytes as well as in the interstitial fluid of rat adipose tissue. A possible role of Ang II in the control of the autocrine-paracrine adipogenic effect of PGI2 has been investigated, using cells of the Ob1771 preadipocyte clonal line cultured in serum-free chemically defined medium. Whereas both preadipose and adipose cells were able to produce PGI2 upon exposure to arachidonic acid, only adipose cells were able to do so when challenged with Ang II. In agreement with this observation, the ability of Ang II to induce preadipose cells to differentiate required the simultaneous presence of differentiated cells. Such coculture experiments show that the promoting effect of Ang II on preadipose cell differentiation was strongly reduced by aspirin, antibodies able to neutralize PGI2, and the AT2 receptor antagonist PD123177, but not by the AT1 receptor antagonist losartan. Together, these results support Ang II as being able, by means of binding to a receptor of the AT2 subtype present in adipose cells, to control the adipogenic effect of PGI2 through a paracrine mode of action.
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PMID:Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin-II. 795 25

Angiotensin II and angiotensin III stimulated prostacyclin release in a time- and dose-dependent manner in both the prostatic and the non-prostatic part of the rabbit vas deferens. Also, angiotensin I enhanced the production of prostacyclin and its effect was blocked by captopril. Losartan, a type 1 (angiotensin AT1)-selective receptor antagonist, prevented the angiotensin II-induced prostacyclin release. The agonist peptide, p-aminophenylalanine angiotensin II, and the type 2 (angiotensin AT2)-selective receptor antagonist, PD123319, were found active only in the prostatic portion, suggesting heterogeneity of the receptor population. In conclusion, an angiotensin AT1 receptor mostly mediates the angiotensin-induced release of prostacyclin in the rabbit vas deferens.
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PMID:Angiotensins induce the release of prostacyclin from rabbit vas deferens: evidence for receptor heterogeneity. 802 65

We determined the role of AT1 and AT2 angiotensin receptors as mediators of prostaglandin (PG) release and mobilization of intracellular Ca++ in cultures of porcine vascular smooth muscle cells (VSMC) with subtype-selective angiotensin (Ang) II receptor antagonists. The binding of [125I]Ang II to porcine VSMC showed an equilibrium constant (KD) of 0.52 nM and a binding capacity (Bmax) of 14.8 fmol/mg protein. Using the AT1 antagonists DuP 753, its metabolite EXP 3174, and L-158,809, [125I]Ang II binding was displaced in a clearly biphasic manner, indicating the presence of two binding sites. Consistent with this, the AT2 antagonist CGP 42112A also displayed a biphasic curve, whereas another AT2 antagonist, PD 123177, showed a 20% reduction in binding. Ang I, Ang II and Ang-(1-7) stimulated PGE2 as well as PGI2 synthesis in a dose-dependent pattern. Ang II but not Ang I or Ang-(1-7) also caused an increase in the intracellular concentration of Ca++. Ca++ mobilization by Ang II was blocked by the AT1 antagonist DuP 753, but not by the AT2 antagonists. Ang II- and Ang I-stimulated (10 nM) PG production was attenuated by all three AT1 antagonists. However, both CGP 42112A (100 nM) and PD 123177 (100 nM) also attenuated PG release in response to Ang II. The enhancement in PG release by Ang I (10 nM) was significantly reduced by CGP 42112A (100 nM), but not by PD 123177 (1 microM). Of the AT1 antagonists, only high doses of DuP 753 or L-158,809 partially reduced the Ang-(1-7)-induced release of PG. CGP 42112A was ineffective for blocking Ang-(1-7)-stimulated PG release. Ang-(1-7)-stimulated PGE2 and PGI2 production was significantly reduced by PD 123177. Unlike DuP 753 or L-158,809, but similar to the sarcosine antagonists, EXP 3174 (10 nM) abolished the angiotensin peptide-induced PG production. These data show that Ang I and Ang II stimulate PGE2 and PGI2 release via activation of both AT1 and AT2 receptors in porcine VSMC. Ang II stimulates intracellular Ca++ mobilization via activation of AT1 receptors only. Because Ang-(1-7) enhanced PGE2 and PGI2 release via activation of angiotensin receptors having greater affinity for PD 123177 than CGP 42112A, although CGP 42112A showed a greater ability to block the Ang I response, these data further suggest differences in these two compounds at AT2 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential regulation of prostaglandin synthesis by angiotensin peptides in porcine aortic smooth muscle cells: subtypes of angiotensin receptors involved. 849 14

The adequate biological function of the renin-angiotensin system in blood pressure regulation and volume control involves additional factors for a fully balanced response. This includes arachidonic acid-derived lipid mediators, the eicosanoids. Angiotensin II (Ang II) causes (AT1)-receptor mediated stimulation of phospholipase C, resulting in generation of IP3 (inositol triphosphate) and activation of protein kinase C, elevated cytosolic Ca+ and stimulation phospholipase A2. These processes culminate in the generation of cell-specific eicosanoids and their autocrine action on the generating cell or paracrine effects on cells in the vicinity. In vascular tissue, liberated arachidonic acid is mainly converted into vasodilator prostaglandins, i.e. prostacyclin (PGI2) and PGE2. These prostaglandins may attenuate any direct Ang II-induced vasoconstriction, lower systemic vascular resistance and stimulate renal sodium excretion. In some vessels, arachidonic acid released by Ang II may also be converted to vasoconstrictor eicosanoids, i.e. thromboxane A2, PGF2 alpha and 12-HETE. The biological significance of endogenous eicosanoid generation becomes evident if vasoactive eicosanoids become limiting factors for maintaining homoiostasis, i.e. in the fetal circulation, Bartter's syndrome and congestive heart failure where vasodilating eicosanoids (PGE2, PGI2) are involved in maintenance of low vascular resistance and reduced or absent vasoconstriction by Ang II. Vasoconstrictor eicosanoids (thromboxane A2, PGF2 alpha, 12-HETE) contribute to high blood pressure in (renovascular) hypertension and pregnancy-induced hypertension. Alternatively, generation of vasodilator prostaglandins may be reduced in these situations. The vascular renin-angiotensin system is subject to the action of a number of drugs and chemicals, most notably specific inhibitors of the angiotensin-converging enzyme and drugs affecting kidney function (furosemide) and/or vessel tone (propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin-mediated actions of the renin-angiotensin system. 849 70


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