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Results for “Angiotensin II”

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PubMed1995

Effects of des-Asp-angiotensin I on the contractile action of angiotensin II and angiotensin III.

Nanomolar concentrations of des-Asp-angiotensin I potentiated the contractile action of angiotensin II on the rabbit aortic ring but attenuated the contractile action of angiotensin III in the same tissue. Indomethacin had no effect on the potentiation of angiotensin II but inhibited the attenuation of angiotensin III. The action of angiotensin II, angiotensin III and des-Asp-angiotensin I was not inhibited by (S)-1-}[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl )-4,5,6, 7-tetrahydro-1H-imidazo-[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate (PD123319), an angiotensin AT2 receptor antagonist. The data show that angiotensin II and angiotensin III act on different subclasses of angiotensin receptors and that their actions are differentially modulated by des-Asp-angiotensin I. The data also indicate the possibility that des-Asp-angiotensin I is a functional peptide that modulates the contractile action of the two angiotensins at sub-nanomolar concentrations.

Angiotensin I↗

PubMed2004

Transforming growth factor beta receptor endoglin is expressed in cardiac fibroblasts and modulates profibrogenic actions of angiotensin II.

Angiotensin II (Ang II) is a powerful mediator of adverse cardiac remodeling and fibrosis. However, the mechanisms of Ang II-induced myocardial fibrosis remain to be clarified. We postulated that Ang II alters transforming growth factor beta (TGF-beta) receptor expression, specifically that of endoglin, and thereby modulates cardiac fibroblast (CF) collagen metabolism. Experiments were conducted using CF from adult Sprague Dawley rats to determine the expression of TGF-beta1 receptors including endoglin, and the role of Ang II type 1 (AT1) and type 2 (AT2) receptors, and MAPK p42/44 in this process. The functional role of endoglin in modulating Ang II effects on matrix metalloproteinase-1 (MMP-1) and type I collagen expression was also analyzed. Endoglin gene and protein expression were consistently identified in quiescent CFs. Ang II increased the expression of endoglin mRNA and protein in a concentration and time-dependent manner, with no effect on TGF-beta receptors I and II expression. This effect was AT1 receptor mediated, because AT1 receptor antagonists valsartan, candesartan, and losartan inhibited Ang II-induced endoglin expression, whereas the AT2 receptor antagonist PD123319 had no effect. MAPKp42/44 inhibition attenuated Ang II-induced endoglin expression. Ang II-induced decrease in MMP-1 protein expression and increase in type I collagen protein expression were both blocked by a specific endoglin antibody. Hence, our results indicate that endoglin is upregulated in CFs by Ang II via the AT1 receptor and modulates profibrotic effects of Ang II. These findings provide novel insights into Ang II-induced cardiac remodeling.

Angiotensin II↗

PubMed1975

Effect of angiotensin II and of an angiotensin II analogue (Sar1-Ile8-angiotensin II) on blood pressure, plasma aldosterone and plasma renin activity in the dog.

1. The effect of infusions of equimolar doses of angiotensin II (AII) and of the angiotensin analogue Sar1-Ile8-angiotensin II on arterial blood pressure, plasma aldosterone and plasma renin activity were compared in normal anaesthetized dexamethasone suppressed dogs. 2. Angiotensin II induced a significant increase of blood pressure and of plasma aldosterone whereas plasma renin activity decreased. The blood pressure was only slightly affected by large doses of the analogue. Plasma aldosterone, however, increased and plasma renin activity decreased. These changes were significant but less pronounced than after the infusions of angiotensin II. Plasma aldosterone remained high and renin activity low for 40 min after the infusions of the analogue. 3. The results suggest a strong agonistic potency of Sar1-Ile8-angiotensin II at the adrenal and renal angiotensin receptors, and that it is almost ineffective at the vascular receptors. The inhibition of renin secretion by angiotensin seems not be related to its vasoconstrictive activity.

Aldosterone↗

PubMed2005

Coexpression of AT1 and AT2 receptors by human fibroblasts is associated with resistance to angiotensin II.

Angiotensin II (AngII) is considered as a cytokine-like factor displaying a variety of proinflammatory and profibrotic cellular effects. Most of these effects seem mediated by AT1 signaling, whereas AT2 expression and function in adult human cells remain unclear. We have studied AT1 and AT2 expression in different human adult fibroblasts types and analyze their response to AngII. AngII did not induce thymidine incorporation, apoptosis nor collagen gene or protein expression in human fibroblasts. Specific AT1 or AT2 inhibitors did not modify this apparent resistance to AngII. We found abundant expression of both AT1 and AT2 receptors in all human fibroblasts studied, whereas vascular smooth muscle cells (VSMC) which only expressed AT1 receptor, displayed a clear AT1-dependent proliferative response to AngII. These data demonstrate that cultured human adult fibroblasts express both AT1 and AT2 receptor types and this phenomenon is associated with a lack of growth or collagen synthesis responses to AngII.

Adult↗

PubMed1986

A glial high-affinity binding site with specificity for angiotensin II not angiotensin III: a possible N-terminal-specific converting enzyme.

Anomalous binding properties of angiotensin II to fetal rat brain primary cultures suggested a possible contribution from contaminating glia. To investigate this possibility, cultures of C6 glioma, a clonal rat cell line, were examined for the presence of angiotensin II receptors. A specific high-affinity site for [125I]angiotensin II was measured both by traditional methodology using whole cells and by autoradiography. This site shared properties similar to that found with the brain cells, namely low ligand internalization and markedly decreased affinity for N-terminal sarcosine or arginine-angiotensin analogs. The competition rank order was angiotensin II much greater than (Sar1,Ile8)angiotensin II greater than or equal to des(Asp1,Arg2)angiotensin II. Angiotensin III did not compete for binding to the site. High-pressure liquid chromatography analysis indicated that the ligand either in the incubation or bound to the site was stable at 15 degrees C, but there was very rapid and extensive degradation by the C6 glioma cells at 37 degrees C. It is concluded that the site exhibits unusual N-terminal specificity for angiotensin with nanomolar affinity for angiotensin II. If angiotensin III is an active ligand in the brain, the site may have a converting enzyme function. Alternatively, it may form the des-Asp derivatives of angiotensin for subsequent degradation by other enzymatic pathways. Either way, it is proposed that the site may modulate the brain-angiotensin system.

Angiotensin II↗

PubMed2001

Differential activation of the STAT pathway by angiotensin II via angiotensin type 1 and type 2 receptors in cultured human fetal mesangial cells.

The vasoactive peptide angiotensin II is the principal effector of the renin-angiotensin system. It exerts mitogenic and growth-inhibiting effects in many target tissues, including renal mesangial cells. To investigate mechanisms of angiotensin II signaling in human mesangial cells, we explored the signal transducer and activator of transcription (STAT) pathway as a possible regulator of angiotensin II receptor-specific signaling. We tested whether angiotensin II could induce STAT activation and nuclear translocation of STAT proteins in human mesangial cells by electromobility shift assays and by immunostaining and confocal microscopy. We found that fetal human mesangial cells express STAT1,2,3,5, and 6 and that stimulation of these cells by angiotensin II results in rapid induction of STAT1 and STAT5 DNA-binding activity. This DNA-binding activity was identified as STAT5 for angiotensin receptor type 1 activation and STAT1 for angiotensin receptor type 2-mediated activation, as induction of STAT-DNA binding by angiotensin II could be differentially blocked by the angiotensin receptor type 1 blocker losartan and by angiotensin II receptor type 2 blocker PD 123,319. Angiotensin II also induced STAT1 and STAT5 tyrosine phosphorylation and nuclear translocation of activated STATs in a receptor subtype-specific manner. STAT activation thus appears to provide an important signaling pathway for angiotensin II-induced cellular responses.

Angiotensin II↗

PubMed1992

Differential actions of angiotensin II and angiotensin-(1-7) on transmitter release.

The central cardiovascular and dipsogenic effects of angiotensin II involve interactions with norepinephrine, dopamine, and serotonin. Our findings that angiotensin II receptors and substance P immunoreactivity show a parallel distribution in the dorsal medulla and that angiotensin II releases substance P from perfused rat medulla slices revealed the potential for a functional relation between these peptidergic systems as well. Additional evidence suggests that the heptapeptide angiotensin-(1-7) exerts its biological activities via selective angiotensin receptor subtypes. Thus, we compared the effects of these two peptides on release of substance P and monoamines in perfused slices of medulla and hypothalamus from 77 male Sprague-Dawley rats. Transmitter levels were determined in 6-minute collections of perfusate before (basal), during (experimental), and after (recovery) perfusion with either angiotensin-(1-7), angiotensin II, or Krebs' solution alone (control). Substance P was measured by radioimmunoassay and monoamines and their metabolites by high-performance liquid chromatography with electrochemical detection. In the medulla, 2 microM angiotensin II but not angiotensin-(1-7) significantly increased efflux of substance P (221 +/- 87% of basal) and norepinephrine (130 +/- 17% of basal) during the experimental period. The effect of angiotensin II on substance P was sustained into the recovery period. Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were not detected in this brain region. In the hypothalamus, both angiotensin-(1-7) and angiotensin II increased substance P (169 +/- 30% and 141 +/- 35% of basal, respectively); the effect of angiotensin II was sustained throughout the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMed1974

Angiotensin II- and angiotensin 3-induced aldosterone release vivo in the rat.

The potential role of angiotensin II and its heptapeptide metabolite, des-aspartyl-angiotensin II, was studied in the conscious unanesthetized rat. Aldosterone release was induced by both peptides at physiologic doses (0.72 nanogram per minute). [I-Sarcosyl-8-alanyl]-angiotensin II (P-113 inhibited angiotensin II more effectively than des-aspartyl-angiotensin II (101 percent as compared to 82 percent). These results indicate that angiotensin controls aldosterone release in the rat and that des-aspartyl-angiotensin II (that is, angiotensin III) may be important in this sequence.

Alanine↗

PubMed1984

Saralasin increases activity of hippocampal neurons inhibited by angiotensin II.

Angiotensin II (AII) has previously been shown to specifically excite neurons in several areas of the rat brain including the hippocampus. Using a brain slice preparation for extra- and intracellular recording, we have found a small proportion of hippocampal neurons which were inhibited by AII. By applying saralasin to those pyramidal cells which are inhibited by AII, we have tested for excitatory effects of saralasin. The results showed that saralasin antagonizes AII whether its effects are inhibitory or excitatory. Saralasin alone generally decreases spontaneous activity and the results indicate that this effect may be due to an inhibition of endogenous brain angiotensin II.

Action Potentials↗

PubMed1973

Subfornical organ: site of drinking elicitation by angiotensin II.

Angiotensin II applied directly to the subfornical organ in a dose as small as 0.1 nanogram elicited short-latency drinking behavior in water-sated rats. Lesions in the body of this structure blocked drinking induced by angiotensin II applied to the basal telencephalon (including preoptic area). These results call attention to the subfornical organ as an important central nervous structure involved in the conrol of drinking behavior.

Angiotensin II↗

PubMed1990

Implication of phospholipase C in the steroidogenic action of angiotensin II.

Angiotensin II (AII) is a major regulator of aldosterone synthesis and secretion by the adrenal zona glomerulosa. Although it has been suggested by many authors that AII acts by increasing the turnover of inositol-lipids, these studies were mainly focussed on the identity and on the kinetics of appearance of inositol phosphates. The purpose of the present study was to establish a relationship between phospholipase C activation and steroidogenesis in the adrenal cortex. A primary culture of bovine adrenal glomerulosa cells was used. Dose-response curves for receptor occupation, inositol phosphate production and aldosterone secretion were made under the same experimental conditions, on the third day of culture. 125I-[Sar1, Val5, D-Phe8]AII binding to glomerulosa cells was progressively inhibited by increasing concentrations of AII up to 30 nM. Scatchard analyses showed a Kd of 1.9 +/- 1.1 nM and a maximal binding capacity of 49,000 +/- 4,500 receptors/cell (six experiments). Dose-response curves for AII-induced inositol 1,4,5-trisphosphate production showed an EC50 of 0.5 +/- 0.1 nM (five experiments). The threshold dose for AII-induced inositol phosphates was around 0.1 nM and the maximal effect was obtained with 30 nM AII. The AII-stimulated steroidogenesis occurred at a threshold dose around 0.03 nM and the maximal effect was obtained with 10 nM AII with an EC50 of 0.5 +/- 0.1 nM (five experiments). These results support previous suggestions that phospholipase C is involved in the steroidogenic action of angiotensin II.

Aldosterone↗

PubMed1998

Janus kinase 2 (Jak2) must be catalytically active to associate with the AT1 receptor in response to angiotensin II.

Angiotensin II evokes a variety of biological responses by binding to a seven transmembrane cell surface receptor termed AT1. Ligand binding to the AT1 receptor induces the physical association and activation of the intracellular kinase Jak2. To elucidate the mechanism of this association, COS-7 cells were co-transfected with the AT1 receptor and either wild type Jak2 or a catalytically inactive Jak2. AT1 receptor-Jak2 association was assessed in vitro by a GST-AT1 receptor fusion protein binding assay and in vivo by direct co-immunoprecipitation of the receptor-Jak2 complex. Both studies showed that Jak2 must be catalytically active to form a complex with the AT1 receptor, and that complex formation is associated with Jak2 tyrosine phosphorylation. These results were confirmed using the Jak2 specific inhibitor AG-490. We also found that over-expression of wild type Jak2 in COS-7 cells leads to in vivo complex formation of spontaneously autophosphorylated Jak2 with the AT1 receptor. No such complex formation was observed with a dominant negative Jak2. Thus, the physical association of Jak2 with the AT1 receptor is regulated by an angiotensin II mediated autophosphorylation event.

Angiotensin II↗

PubMed1992

Mobilization of calcium from intracellular store as a possible mechanism underlying the anti-opioid effect of angiotensin II.

Angiotensin II (AII), injected intracerebroventricularly, has been shown to antagonize opioid analgesia. The mechanism for this was obscure. In the neuroblastoma X glioma NG 108-15 hybrid cell line, the K(+)-induced increase in [Ca2+]i can be suppressed by the delta opioid agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) at 0.01-1 microM, an effect completely reversed by the opioid antagonist naloxone. Angiotensin II (AII) at concentrations of 0.1 and 1 microM mobilized free Ca2+ from an intracellular pool, and this effect was antagonized by the AII receptor antagonist saralasin. All (1 microM) had no significant effect on the increase in [Ca2+]i induced by K+, but it blocked the suppressive effect of DPDPE on the K(+)-induced [Ca2+]i increase. The results indicate that mobilization of intracellular calcium may underlie the anti-opioid effect of AII.

Angiotensin II↗

PubMed1995

Regulation of luminal alkalinization and acidification in the cortical collecting duct by angiotensin II.

Angiotensin II (ANG II) regulates whole kidney ion transport, yet its effects in the collecting duct are unknown. The purpose of these studies was to determine whether ANG II regulates luminal alkalinization and acidification in the rabbit cortical collecting duct (CCD). The rate of luminal alkalinization or acidification was measured as the rate of change of luminal fluid pH under stop-flow conditions using in vitro microperfused CCD segments. Outer CCD alkalinized the luminal fluid, consistent with net HCO3- secretion. Addition of ANG II, 10(-7) M, to the peritubular solution for 30 min significantly stimulated luminal alkalinization. The stimulatory effect of ANG II was not due to time-dependent effects and was blocked by peritubular addition of the ANG II type 1 (AT1) receptor antagonist, losartan, at 10(-6) M. Losartan, 10(-6) M, when added to the peritubular solution, did not alter the rate of luminal alkalinization independent of ANG II. In contrast, peritubular ANG II, 10(-7) M, did not alter inner CCD luminal acidification. Addition of ANG II to the peritubular solution at the lower concentration of 10(-10) M did not alter the rates of luminal alkalinization and acidification in the outer and inner CCD, respectively. Peritubular ANG II, 10(-7) M, but not vehicle, stimulated B cell apical HCO3- secretion occurring in response to peritubular Cl- removal. These studies demonstrate that ANG II acts through a basolateral AT1 receptor to stimulate outer CCD luminal alkalinization via, at least in part, B cell stimulation.

Acids↗

PubMedDate not supplied

Effects of sinoaortic denervation on glucose utilization in the subfornical organ and pituitary neural lobe during administration of angiotensin II.

Angiotensin II infused intravenously into sinoaortic-denervated rats induced drinking and increased glucose utilization in the subfornical organ and pituitary neural lobe in amounts not different from those observed in sham-operated animals. We suggest that inputs from baroreceptors have a negligible influence on glucose metabolism in the subfornical organ during infusion of angiotensin II.

Animals↗

PubMed1994

Proteinuric potentials of angiotensin II, [des-Asp1]-angiotensin II, and [des-Asp1, des-Arg2]-angiotensin II in rats.

To compare proteinuric potentials among angiotensin II (ANG II) and its fragments, [des-Asp1]-angiotensin II (ANG III) and [des-Asp1, des-Arg2]-angiotensin II (ANG IV), the peptide was intravenously infused for 30 min at doses of 0.015, 0.05, 0.15, 0.45 and 1.45 nmol/kg body weight/min. The infusion of ANG II and ANG III increased the fractional clearance of albumin in a dose-dependent manner: most extensively for ANG II, and moderately for ANG III. In contrast, the infusion of ANG IV hardly showed any proteinuric action, even at the maximal dose of 1.45 nmol/kg body weight/min. These results denoted that the cleaving of the N-terminal aspartic acid1 from ANG II weakened the proteinuric action in the glomeruli, and the further cleaving of the N-terminal arginine from ANG III led to a complete loss of proteinuric action in the glomeruli.

Angiotensin II↗

PubMed1975

[Metabolism of angiotensin II during angiotensin infusion and following sodium depletion].

1. Angiotensin II (A II) and angiotensin (3--8)-hexapeptide (H) were measured by radioimmunoassay in arterial and venous plasma before and during infusion of angiotensin II-amide in five normotensive subjects, both in sodium-replete and sodium-depleted states. The separation of the oligopeptides was performed by thin layer chromatography. 2. Before sodium-depletion the mean ratio of arterial to venous A II was 1.14+/-0.11:1, corresponding to an A II-extraction of approximately 12% during a single forearm passage. Infusion of A II-amide increased extraction of A II. The mean ratio of arterial to venous A II increased to 1.68+/-0.3:1, corresponding to an extraction of approximately 39% when 8 ng-min-1-kg-1 were infused. 3. Sodium depletion increased arterial and venous concentrations of A II and H. During infusion of angiotensin II-amide the arterial and venous concentrations of A II and H increased approximately parallel to the concentrations before sodium depletion. The extraction of A II did not differ significantly in both states. 4. The augmented extraction extraction of A II observed during infusion of angiotensin II-amide suggest an overproportional increase of the metabolism of A II under the latter condition. Sodium depletion, however, does not appear to cause a percent change in A II metabolism.

Adult↗

PubMed1995

Modulation of cardiac autonomic control in humans by angiotensin II.

Angiotensin II (Ang II) exerts an inhibitory action on vagal activity in animals and may also facilitate sympathetic activity. The object of this study was to compare autonomic activity resulting from equivalent steady-state baroreflex activation during intravenous Ang II infusion with that resulting from a control infusion of phenylephrine. Eight healthy subjects aged 22 to 34 years were studied in a single-blind, randomized, prospective crossover study. Autonomic activity was determined by computer analysis of RR interval variability in the time and frequency domains. Despite equal experimental hypertension with Ang II and phenylephrine infusion, at peak infusion rates the mean RR interval was significantly shorter with Ang II (983 +/- 179 milliseconds; mean +/- SD) than with phenylephrine (1265 +/- 187 milliseconds, P < .01). The variability of RR intervals was not significantly different, but the variability (median interquartile difference) of RR interval successive differences was significantly lower with Ang II (66 milliseconds) than with phenylephrine (104 milliseconds, P < .02). Power spectral analysis revealed the power of the 0.25-Hz component in normalized units to be significantly smaller during Ang II infusion (20.5 +/- 12.7 U) than during phenylephrine (38.2 +/- 14.7 U, P < .05), whereas the power of the 0.1-Hz component was significantly greater during Ang II infusion (67.8 +/- 17.1 U) than phenylephrine (38.8 +/- 20.3 U, P < .05). Measures of vagal modulation of heart rate were significantly attenuated, and sympathetic modulation appeared to be increased during Ang II infusion compared with control phenylephrine infusions. These observations may underlie reports of increased vagal activity during angiotensin-converting enzyme inhibitor therapy.

Adult↗