Proteolytic Conversion of Angiotensins in Rat Brain Tissue

Tonnaer, J. A. D. M.; Engels, G.M.H.; Wiegant, V.M.; Burbach, J. Peter H.; Jong, W. De; Wied, D. de

doi:10.1111/j.1432-1033.1983.tb07279.x

Cited by 60 publications

(31 citation statements)

References 35 publications

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“…by guest on May 8, 2018 http://hyper.ahajournals.org/ Downloaded from does not cause pressor or drinking responses, 30 it has been proposed that the heptapeptide acts as a subset of angiotensin receptors. In the rabbit vas deferens, Trachte et al 27 showed that, unlike Ang II and Ang-(2-8), Ang-(l-7) had no direct vasoconstrictor activity and did not alter release of norepinephrine even though it was a potent stimulus for PGE release.…”

Section: Discussionmentioning

confidence: 99%

Human astrocytes contain two distinct angiotensin receptor subtypes.

et al. 1991

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The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and VVITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E, and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(l-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(l-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(l-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides -angiotensin-(1-7) and angiotensin-(2-8). Furthermore, the data also suggest that preferential production of angiotensin-(1-7) and angiotensin-(2-8) may be one level of regulation whereby a particular signal transduction pathway [i.e., calcium mobilization by angiotensin-(2-8) or prostaglandin release by angiotensin-(l-7)] is selectively activated. {Hypertension 1991;18:32-39)

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Section: Discussionmentioning

confidence: 99%

Human astrocytes contain two distinct angiotensin receptor subtypes.

et al. 1991

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“…We favor this latter hypothesis because the actions of the two peptides are not always identical. For example, although both Ang II and Ang-(l-7) cause vasopressin release 21 and produce cardiovascular effects in the dorsal medulla, Ang-(1-7) is devoid of dipsogenic actions 22 and does not produce pressor responses after injections into the brain ventricles. Additionally, the potentiation of the response to Ang-(l-7) after denervation may also reflect the presence of different receptors for the two peptides, possibly situated on different parts of the neuronal circuits comprising the baroreceptor reflex arc.…”

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confidence: 99%

Actions of angiotensin peptides after partial denervation of the solitary tract nucleus.

1990

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We determined the excitatory effects of direct nucleus tractus solitarii injection of angiotensin peptides after the sinoaortic nerves were cut unilaterally in rats under halothane anesthesia. Twenty-four hours later, recordings of mean arterial pressure and heart rate were obtained during injections of 2.5 ng angiotensin II or angiotensin-(l-7) in chloralose-urethaneanesthetized rats. Both peptides caused reductions in pressure and heart rate after nucleus tractus solitarii injections. In unilateral sinoaortic denervated rats, the hypotension and bradycardia produced with angiotensin II injections in either the ipsilateral (denervated) or contralateral (nondenervated) nucleus tractus solitarii were comparable. Angiotensin-(l-7), however, produced a larger decrease in pressure on the denervated side when compared with the nondenervated side. There were no differences in baseline pressure or heart rate between control rats and those with unilateral sinoaortic denervations. The effects of both angiotensin II and angiotensin-(l-7) were blocked by previous administration of the angiotensin II antagonist [Sar',Thr 8 ]angiotensin II into the nucleus tractus solitarii. Assessment of angiotensin II binding sites in the solitary-vagal complex 24 hours after denervation showed a 13% reduction in angiotensin receptors. These findings confirm that both angiotensin II and angiotensin-(1-7) express biological activity through receptor-mediated actions in the dorsal medulla oblongata. That the effects produced by angiotensin II do not require the integrity of baroreceptor input further suggests that the receptors responsible for the acute cardiovascular actions of this peptide reside on postsynaptic elements in the vagal-solitary complex. {Hypertension 1990;15(suppl I):I-34-I-39)

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“…1,2 An early study reported pressor effects in humans in vivo but used such large doses that it was regarded as confirmation of biological inactivity (0.028% of the activity of Ang II). 3 It has since emerged that Ang-(1-7) is biologically active in the central nervous system 4 and indeed in the circulation.…”

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Effect of Angiotensin-(1-7) and Bradykinin in Patients With Heart Failure Treated With an ACE Inhibitor

Davie

McMurray

1999

Hypertension

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Abstract-Angiotensin-(1-7) is a product of angiotensin processing that has been proposed to have vasodepressor effects, both on its own and in combination with bradykinin, which may be pathophysiologically and therapeutically important. Despite this, there has been very little examination of its effects in humans and none in heart failure patients or in other patients treated with ACE inhibitors. We therefore sought to determine the effects of angiotensin-(1-7) in patients with heart failure treated with an ACE inhibitor, as well as any interaction with the effects of bradykinin. A locally active dose of angiotensin-(1-7), alone and in combination with bradykinin, was infused into the nondominant brachial artery while forearm blood flow was measured by venous occlusion plethysmography in 8 patients with heart failure treated with ACE inhibitors. Although bradykinin on its own caused profound vasodilation, there was no effect of angiotensin-(1 to 7) on its own or any effect of angiotensin-(1-7) on the response to bradykinin. We conclude that angiotensin-(1-7) is biologically inactive in the forearm circulation of patients with heart failure treated with an ACE inhibitor. The contrast between these findings and previously reported preclinical findings calls into question the relevance of angiotensin-(1-7) to the hemodynamic effects of ACE inhibitors. (Hypertension. 1999;34:457-460.)

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Proteolytic Conversion of Angiotensins in Rat Brain Tissue

Cited by 60 publications

References 35 publications

Human astrocytes contain two distinct angiotensin receptor subtypes.

Human astrocytes contain two distinct angiotensin receptor subtypes.

Actions of angiotensin peptides after partial denervation of the solitary tract nucleus.

Effect of Angiotensin-(1-7) and Bradykinin in Patients With Heart Failure Treated With an ACE Inhibitor

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