Autoradiographic localization of angiotensin receptors in the sheep brain

McKinley, Michael J.; Allen, Andrew M.; Clevers, J.C.; Denton, Derek A.; Mendelsohn, Frederick A.O.

doi:10.1016/0006-8993(86)90761-4

Cited by 67 publications

(19 citation statements)

References 13 publications

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“…The sites of highest density were in the paraventricular nucleus of the hypothalamus (PVN), the nucleus of the solitary tract (NTS) and the dorsal motor nucleus (DMN) (Figure 4), as has been noted previously in sheep 25 . The receptor type was predominantly AT 1 R in all regions examined, because co-incubation with losartan decreased the binding intensity to background levels.…”

Section: Resultssupporting

confidence: 76%

Central Angiotensin Type 1 Receptor Blockade Decreases Cardiac But Not Renal Sympathetic Nerve Activity in Heart Failure

et al. 2012

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In heart failure (HF) cardiac sympathetic nerve activity (CSNA) is increased, which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is evidence that the central renin angiotensin system plays an important role in stimulating renal SNA (RSNA) in HF. Since SNA to individual organs is differentially controlled, we have investigated whether central angiotensin receptor blockade decreases CSNA in HF. We simultaneously recorded CSNA and renal SNA (RSNA) in conscious normal sheep and in sheep with HF induced by rapid ventricular pacing (ejection fraction <40%). The effect of blockade of central angiotensin AT1R by intracerebroventricular infusion of losartan (1 mg/h for 5 hrs) on resting levels and baroreflex control of CSNA and RSNA was determined. In addition, the levels of angiotensin receptors in central autonomic nuclei were determined using autoradiography. Sheep in HF had a large increase in CSNA (43±2 to 88±3 bursts/100 heart beats, P<0.05) and heart rate, with no effect on RSNA. In HF, central infusion of losartan for 5 hours significantly reduced the baseline levels of CSNA (to 69±5 bursts/100 heart beats) and heart rate. Losartan had no effect in normal animals. In HF, angiotensin receptor levels were increased in the paraventricular nucleus and supraoptic nucleus, but reduced in the area postrema and nucleus tractus solitarius. In summary, infusion of losartan reduced the elevated levels of CNSA in an ovine model of HF, indicating that central angiotensin receptors play a critical role in stimulating the increased sympathetic activity to the heart.

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Section: Resultssupporting

confidence: 76%

Central Angiotensin Type 1 Receptor Blockade Decreases Cardiac But Not Renal Sympathetic Nerve Activity in Heart Failure

et al. 2012

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“…Our measurement of low amounts of Ang II, but not Ang I, in ME suggests that these low amounts of Ang II are not due to the trapping of blood in the tissue. However, these low amounts of Ang II may be derived from blood because the sheep ME contains a high level of angiotensin receptors [43] to which Ang II in the ME may be bound. Moreover, the high level of prolyl endopepti dase activity in the ME is consistent with the proposal that the increased Ang-(l-7) in portal plasma is due to enhanced metabolism of Ang I delivered to the ME by arterial blood.…”

Section: Discussionmentioning

confidence: 99%

Increased Angiotensin-(1–7) in Hypophysial-Portal Plasma of Conscious Sheep

Lawrence

Clark²,

Campbell³

1992

Neuroendocrinology

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Studies were undertaken to characterize angiotensin peptides in hypophysial-portal blood of conscious sheep and to determine whether the median eminence (ME) secretes angiotensin peptides into the hypophysial-portal circulation. Simultaneous measurements of angiotensin peptides in jugular and hypophysial-portal plasma were performed in 6 sheep. Cerebrospinal fluid (CSF) was collected and data for hypophysial-portal plasma were corrected for CSF contamination. Angiotensin peptides were also measured in extracts of sheep ME. In a separate group of 4 sheep, simultaneous measurements of angiotensin peptides in arterial and jugular plasma were performed. Using high performance liquid chromatography-based radioimmunoassays, 8 angiotensin peptides were measured: Ang-(1–7), Ang II, Ang-(1–9), Ang I, Ang-(2–7), Ang III, Ang-(2–9), and Ang-(2-10). Renin, angiotensinogen and prolyl endopeptidase were also measured. No differences in angiotensin peptide levels in arterial and jugular plasma were observed. Angiotensin peptide levels in hypophysial-portal plasma were similar to those in jugular plasma, except for Ang-(1–7), the levels of which were 5-fold higher in hypophysial-portal plasma, and Ang I, for which the levels in hypophysial-portal plasma were 46% of the jugular levels. Renin and angiotensinogen levels were similar in arterial, jugular, and hypophysial-portal plasma. Angiotensin peptide contents of sheep ME were < 16 fmol/ME. However, the prolyl endopeptidase content of sheep ME was 430-fold higher than plasma levels. The low levels of angiotensin peptides in sheep ME indicate that it does not secrete these peptides into the hypophysial-portal circulation. Rather, the high level of prolyl endopeptidase in ME is consistent with region-specific metabolism of Ang I delivered to the ME by arterial blood, generating increased levels of Ang-(1–7) in hypophysial portal plasma. The increased levels of Ang-(1–7) in hypophysial-portal plasma may play a role in regulation of pituitary function.

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“…The MnPO and OVLT express AT 1 receptors [17–20], and lesions made in the anteroventral third ventricle region (AV3V), which comprises parts of the MnPO and OVLT, abolish the drinking response to icv AngII [21]. Moreover, c-Fos expression is observed in the AV3V after icv injection of AngII [22, 23], and ventricular obstruction that prevents CSF from reaching the AV3V prevents water intake stimulated by AngII injected into the lateral ventricle [21, 24–26].…”

Section: Introductionmentioning

confidence: 99%

The anteroventral third ventricle region is critical for the behavioral desensitization caused by repeated injections of angiotensin II

Vento

Daniels

2014

Behavioural Brain Research

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A single central injection of angiotensin II (AngII) potently increases water intake; however, a growing body of research suggests that repeated, acute intracerebroventricular injections of AngII cause a reduction in the dipsogenic response to subsequent AngII. This AngII-induced behavioral desensitization is specific to the effects of angiotensin and mediated by the angiotensin type-1 (AT1) receptor. The neuroanatomical substrate for this phenomenon, however, remains unknown. The anteroventral third ventricle region (AV3V) is an important site for the behavioral and physiological actions of AngII. Therefore, we hypothesized that this region also mediates the effects of repeated central AngII administration. In support of this hypothesis, we found that repeated injections of AngII into the AV3V reduced water intake stimulated by a test injection of AngII given into this region. Moreover, repeated AngII injections in the AV3V reduced water intake after AngII was injected into the lateral ventricle. These studies also demonstrate that activation of the AT1 receptor within the AV3V is required for AngII-induced behavioral desensitization because direct injection of the AT1 receptor antagonist, losartan, into the AV3V blocked the desensitizing effect of repeated AngII injections into the lateral ventricle. These findings provide additional support for a role of the AV3V in the dipsogenic actions of AngII, and suggest that this region is critical for the desensitization that occurs after acute repeated central injections of AngII.

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Autoradiographic localization of angiotensin receptors in the sheep brain

Cited by 67 publications

References 13 publications

Central Angiotensin Type 1 Receptor Blockade Decreases Cardiac But Not Renal Sympathetic Nerve Activity in Heart Failure

Central Angiotensin Type 1 Receptor Blockade Decreases Cardiac But Not Renal Sympathetic Nerve Activity in Heart Failure

Increased Angiotensin-(1–7) in Hypophysial-Portal Plasma of Conscious Sheep

The anteroventral third ventricle region is critical for the behavioral desensitization caused by repeated injections of angiotensin II

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