Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary

1997 ◽  
Vol 273 (1) ◽  
pp. E156-E163 ◽  
Author(s):  
G. L. Sanvitto ◽  
O. Johren ◽  
W. Hauser ◽  
J. M. Saavedra
Keyword(s):  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Anterior Pituitary ◽  
Water Deprivation ◽  
Subfornical Organ ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
At1 Receptors ◽  
Receptor Mrna

We studied angiotensin II (ANG II) receptor subtype expression in selected brain nuclei and pituitary gland after water deprivation by in vitro receptor autoradiography using 125I-labeled [Sar1]ANG II and by in situ hybridization using 35S-labeled AT1A, AT1B, and AT2 receptor-specific riboprobes. In control rats we found binding to AT1 receptors in the subfornical organ, paraventricular nucleus, median eminence, and anterior pituitary; AT1A mRNA expression in the subfornical organ and paraventricular nucleus; and AT1B mRNA expression in the anterior pituitary. No receptor mRNA was found in the median eminence. AT1 receptors and AT1A receptor mRNA levels were increased in the subfornical organ, and, in the anterior pituitary, AT1 receptors and AT1B receptor mRNA were increased, only after 5 days of water deprivation. No significant changes occurred after 1 or 3 days of water deprivation, and no regulation of ANG II receptor expression was detected in other brain areas. Our results show that prolonged water deprivation selectively regulates AT1 receptor expression and AT1A and AT1B receptor mRNA levels in the subfornical organ and anterior pituitary, respectively, supporting a role for these receptors during sustained dehydration.

scholarly journals Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2012 ◽  
Vol 215 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Regina Nostramo ◽  
Andrej Tillinger ◽  
Juan M Saavedra ◽  
Ashok Kumar ◽  
Varunkumar Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna ◽  
Receptor Gene Expression

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2 receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2 receptor mRNA levels, but the decline was more transient. AT1A receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1 receptor antagonist) or with CGP42112 (AT2 receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2 receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2 receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2 receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2 receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1A and AT2 receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.

scholarly journals Chronic angiotensin II infusion modulates angiotensin II type I receptor expression in the subfornical organ and the rostral ventrolateral medulla in hypertensive rats

2011 ◽  
Vol 12 (4) ◽  
pp. 440-445 ◽  
Author(s):  
Fabíola C Nunes ◽  
Valdir A Braga
Keyword(s):  
Central Nervous System ◽  
Angiotensin Ii ◽  
Ventrolateral Medulla ◽  
Type I ◽  
Mrna Levels ◽  
Ang Ii ◽  
At1 Receptors ◽  
Receptor Mrna ◽  
Induced Hypertension ◽  
The Central Nervous System

Blood-borne angiotensin II (Ang II) has profound effects on the central nervous system, including regulation of vasopressin secretion and modulation of sympathetic outflow. However, the mechanism by which circulating Ang II affects the central nervous system remains largely unknown. We tested the hypothesis that increased circulating levels of Ang II activate angiotensin type I (AT1) receptors in the subfornical organ (SFO), increasing the Ang II signalling in the rostral ventrolateral medulla (RVLM). Male Wistar rats were subcutaneously implanted with two 14-day osmotic minipumps filled with Ang II (150ng/kg/minute), Losartan (10mg/kg/day), or saline. In addition, AT1 receptor mRNA levels in the SFO and RVLM were detected by reverse transcription polymerase chain reaction (RT-PCR). Infusion of Ang II-induced hypertension (134 ± 10 mmHg vs 98 ± 9 mmHg, n = 9, p < 0.05), which was blunted by concomitant infusion of Losartan (105 ± 8 vs 134 ± 10 mmHg, n = 9, p < 0.05). In addition, hexamethonium produced a greater decrease in blood pressure in Ang II-infused rats. Real time PCR revealed that chronic Ang II infusion induced an increase in AT1 receptor mRNA levels in the RVLM and a decrease in the SFO. Taken together, using combined in vivo and molecular biology approaches, our data suggest that Ang II-induced hypertension is mediated by an increase in sympathetic nerve activity, which seems to involve up-regulation of AT1 receptors in the RVLM and down-regulation of AT1 receptors in the SFO.

Downregulation of ANG II receptor is associated with compensated pressure-overload hypertrophy in the young dog

2002 ◽  
Vol 282 (2) ◽  
pp. H749-H756 ◽  
Author(s):  
David Schultz ◽  
Xuefeng Su ◽  
Chih-Chang Wei ◽  
Sanford P. Bishop ◽  
Pamela Powell ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
Receptor Mrna ◽  
Gradual Onset ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We studied the gradual onset of pressure overload (PO) induced by a mildly constricting aortic band in 8-wk-old puppies ( n = 8) that increased to 98 ± 11 mmHg at 9 mo. Left ventricular (LV) weight/body weight was increased in PO versus sham-operated littermate controls [8.11 ± 0.60 (SE) vs. 4.46 ± 0.38 g/kg, P < 0.001]. LV end-diastolic diameter, diastolic pressure, and fractional shortening did not differ in PO versus control dogs. There were no inducible arrhythmias in response to an aggressive electrophysiological stimulation protocol in PO dogs. Furthermore, isolated cardiomyocyte function did not differ between control and PO dogs. LV angiotensin II (ANG II) levels were increased (68 ± 12 vs. 20 ± 5 pg/g, P < 0.01) as steady-state ANG II type 1 (AT1) receptor mRNA was decreased 40% and endothelial nitric oxide synthase mRNA levels were increased 2.5-fold in PO versus control dogs ( P < 0.05). Total ANG II receptor binding sites of freshly prepared cardiac membranes demonstrated no difference in the dissociation constant, but there was a 60% decrease in maximum binding (Bmax) in PO versus control dogs ( P< 0.01). LV ANG II levels correlated negatively with AT1receptor mRNA levels ( r = −0.75, P < 0.01) and total AT1 receptor Bmax( r = −0.77, P < 0.02). These results suggest that LV ANG II negatively regulates AT1 receptor expression and that this is an adaptive response to chronic PO before the onset of myocardial failure in the young dog.

scholarly journals A novel role for miR-133a in centrally mediated activation of the renin-angiotensin system in congestive heart failure

2017 ◽  
Vol 312 (5) ◽  
pp. H968-H979 ◽  
Author(s):  
Neeru M. Sharma ◽  
Shyam S. Nandi ◽  
Hong Zheng ◽  
Paras K. Mishra ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Paraventricular Nucleus ◽  
Renin Angiotensin System ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

An activated renin-angiotensin system (RAS) within the central nervous system has been implicated in sympathoexcitation during various disease conditions including congestive heart failure (CHF). In particular, activation of the RAS in the paraventricular nucleus (PVN) of the hypothalamus has been recognized to augment sympathoexcitation in CHF. We observed a 2.6-fold increase in angiotensinogen (AGT) in the PVN of CHF. To elucidate the molecular mechanism for increased expression of AGT, we performed in silico analysis of the 3′-untranslated region (3′-UTR) of AGT and found a potential binding site for microRNA (miR)-133a. We hypothesized that decreased miR-133a might contribute to increased AGT in the PVN of CHF rats. Overexpression of miR-133a in NG108 cells resulted in 1.4- and 1.5-fold decreases in AGT and angiotensin type II (ANG II) type 1 receptor (AT1R) mRNA levels, respectively. A luciferase reporter assay performed on NG108 cells confirmed miR-133a binding to the 3′-UTR of AGT. Consistent with these in vitro data, we observed a 1.9-fold decrease in miR-133a expression with a concomitant increase in AGT and AT1R expression within the PVN of CHF rats. Furthermore, restoring the levels of miR-133a within the PVN of CHF rats with viral transduction resulted in a significant reduction of AGT (1.4-fold) and AT1R (1.5-fold) levels with a concomitant decrease in basal renal sympathetic nerve activity (RSNA). Restoration of miR-133a also abrogated the enhanced RSNA responses to microinjected ANG II within the PVN of CHF rats. These results reveal a novel and potentially unique role for miR-133a in the regulation of ANG II within the PVN of CHF rats, which may potentially contribute to the commonly observed sympathoexcitation in CHF. NEW & NOTEWORTHY Angiotensinogen (AGT) expression is upregulated in the paraventricular nucleus of the hypothalamus through posttranscriptional mechanism interceded by microRNA-133a in heart failure. Understanding the mechanism of increased expression of AGT in pathological conditions leading to increased sympathoexcitation may provide the basis for the possible development of new therapeutic agents with enhanced specificity.

Ablation of subfornical organ does not prevent angiotensin-induced water drinking in sheep

1986 ◽  
Vol 250 (6) ◽  
pp. R1052-R1059 ◽  
Author(s):  
M. J. McKinley ◽  
D. A. Denton ◽  
R. G. Park ◽  
R. S. Weisinger
Keyword(s):  
Angiotensin Ii ◽  
Hypertonic Saline ◽  
Water Deprivation ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Water Drinking

The subfornical organ (SFO) and surrounding periventricular tissue were ablated in sheep. Such a lesion did not significantly reduce water drinking in response to intracarotid, intravenous, or intracerebroventricular infusions of [Val5]angiotensin II amide (ANG II) but caused reduced intake of water in response to intracarotid infusion of hypertonic saline. The dipsogenic response of these sheep to water deprivation for 3 days was similar to that of normal sheep subjected to water deprivation. Although the results are not conclusive in excluding the SFO from having a role in ANG II-induced drinking, they show that there are receptors outside the SFO sensitive to blood-borne ANG II that are involved in water drinking in sheep. The results also show that tissue in the SFO or its surroundings may be involved in drinking caused by acute hypertonicity.

Subfornical organ efferents to paraventricular nucleus utilize angiotensin as a neurotransmitter

1993 ◽  
Vol 265 (2) ◽  
pp. R302-R309 ◽  
Author(s):  
Z. Li ◽  
A. V. Ferguson
Keyword(s):  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Response Times ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Neural Responses ◽  
Local Pressure ◽  
Electrophysiological Studies ◽  
Excitatory Responses ◽  
Control Stimulation

In this study, we have utilized electrophysiological single unit recordings to evaluate the effects of nonpeptidergic angiotensin II (ANG II) antagonists on neural responses of hypothalamic paraventricular nucleus (PVN) neurons to either electrical stimulation in subfornical organ (SFO) or direct application of ANG II. Electrical stimulation (200-400 microA; 0.1 ms) in the SFO resulted in excitatory responses in 36 of 50 PVN neurons tested. Peristimulus histogram analysis of such excitatory effects demonstrated latencies of < 30 ms and variability of response times of approximately 50 ms in 14 of these 36 neurons. In view of previous anatomic and electrophysiological studies such inputs were therefore considered to be monosynaptically mediated by direct neural inputs from the SFO. The remaining 22 cells excited by such SFO stimulation showed responses of longer latency and duration suggestive of a different underlying synaptic mechanism. Local pressure ejection of ANG II into the PVN resulted in increased neural activity in 50% (9 of 18) of the neurons tested. After systemic (3 mg/kg iv) or local (2 x 10(-2) M; 1-25 s; 2-40 psi) microinjection of the nonpeptidergic angiotensin II1 (AT1) receptor antagonist losartan, SFO excitations were attenuated in 63.9% (23 of 36) of the PVN neurons tested, such pharmacologically blocked excitatory responses being reduced by 68.3 +/- 5.2% from control stimulation effects (P < 0.001). Similar losartan-induced attenuations of both short latency (presumed monosynaptic) (50.0%) and longer latency (72.7%) responses were observed. In addition, losartan also abolished the excitatory effects of local administration of ANG II on 77.8% (7 of 9) of ANG II-sensitive neurons in PVN tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Water deprivation upregulates angiotensin II receptors in rat anterior pituitary

1985 ◽  
Vol 248 (2) ◽  
pp. E264-E267
Author(s):  
A. Israel ◽  
J. M. Saavedra ◽  
L. Plunkett
Keyword(s):  
Angiotensin Ii ◽  
Anterior Pituitary ◽  
Water Deprivation ◽  
Protein A ◽  
Ang Ii ◽  
Electrolyte Metabolism ◽  
Single Class ◽  
Individual Male ◽  
High Affinity ◽  
Pituitary Glands

Angiotensin II (ANG II) receptors were quantitated in pituitary glands of individual male Long Evans rats by autoradiography after incubation of 8-microns thick pituitary sections with 125I-[Sar1]ANG II. Rat anterior pituitary had a single class of high-affinity saturable ANG II receptors with a Bmax of 1,360 +/- 109 fmol/mg protein and a Ka of 0.510 +/- 0.03 X 10(9) M-1. Five days of water deprivation produced a marked increase in the number of anterior pituitary ANG II receptors (Bmax: 2,428 +/- 233 fmol/mg protein, a 79% increase, P less than 0.001) and a decrease in affinity for the ligand (Ka: 0.337 +/- 0.01 10(9) M-1, a 34% decrease, P less than 0.05). Our results suggest a role for anterior pituitary ANG II receptors in the regulation of fluid and electrolyte metabolism in the rat.

Release of angiotensins in paraventricular nucleus of rat in response to physiological and chemical stimuli

1992 ◽  
Vol 262 (1) ◽  
pp. F17-F23 ◽  
Author(s):  
J. W. Harding ◽  
L. L. Jensen ◽  
J. M. Hanesworth ◽  
K. A. Roberts ◽  
T. A. Page ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Release Rate ◽  
High Performance ◽  
Water Deprivation ◽  
Fold Increase ◽  
High Performance Liquid Chromatographic ◽  
Circumventricular Organs ◽  
Ang Ii ◽  
Direct Infusion ◽  
Angiotensin System

The brain angiotensin (ANG II and III) system is known to play an important role in the central control of cardiovascular function and body water homeostasis. A number of components of the angiotensin system including active peptides, precursors, synthetic enzymes, and receptors have been localized to specific brain nuclei including the paraventricular nucleus (PVN) of the hypothalamus. We and others have hypothesized that the PVN is a major integrative hub of the central angiotensin system receiving angiotensinergic input from central detectors (circumventricular organs) and sending efferents to higher brain and spinal cord centers. Implicit in this idea is that angiotensins, like all neurotransmitters, should be releasable with appropriate chemical and physiological stimuli. Therefore we examined the ability of water deprivation or direct infusion of either 65 mM K+ or 80 microM veratridine to stimulate the release of angiotensins from the PVN of the rat. Using push-pull cannulas to perfuse the PVN and radioimmunoassay (RIA) to analyze the superfusate for immunoreactive angiotensins, we established that 24 h of water deprivation resulted in an approximate 5-fold increase in the angiotensin release rate, whereas 48-h deprivation produced a dramatic 492-fold increase in release. Direct infusion of 65 mM K+ into the PVN was unable to stimulate angiotensin release, but 80 microM veratridine elicited a sevenfold increase in the angiotensin release rate. High-performance liquid chromatographic separation and RIA analysis of veratridine- and water deprivation-stimulated angiotensin release demonstrated that 93.4% of the releasable angiotensin coeluted with ANG III, whereas only 6.8% eluted with authentic ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression

1996 ◽  
Vol 313 (3) ◽  
pp. 873-878 ◽  
Author(s):  
Wei LIAO ◽  
Mats RUDLING ◽  
Bo ANGELIN
Keyword(s):  
Time Course ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Receptor Mrna

Endotoxin induces hyperlipidaemia in experimental animals. In the current study, we investigated whether endotoxin alters hepatic low-density lipoprotein (LDL) receptor expression in rats. Endotoxin treatment suppressed hepatic LDL receptor expression in a dose- and time-dependent manner. Eighteen hours after intraperitoneal injection of increasing amounts of endotoxin, LDL receptor and its mRNA levels were determined by ligand blot and solution hybridization respectively. LDL receptor expression was inhibited by about 70% at a dose of 500 μg/100 g body weight. However, LDL receptor mRNA levels were markedly increased in all endotoxin-treated groups at this time point (by 83–136%; P < 0.001). Time-course experiments showed that LDL receptor expression was already reduced by 48% 4 h after endotoxin injection and was maximally reduced (by 63–65%) between 8 and 18 h. Changes in hepatic LDL receptor mRNA showed a different pattern. By 4 h after endotoxin injection, LDL receptor mRNA had decreased by 78% (P < 0.001). However, by 8 h after endotoxin injection, LDL receptor mRNA had returned to levels similar to controls, and 18 and 24 h after endotoxin injection, they were increased by about 60% (P < 0.05). Separation of plasma lipoproteins by FPLC demonstrated that endotoxin-induced changes in plasma triacylglycerols and cholesterol were due to accumulation of plasma apolipoprotein B-containing lipoproteins among very-low-density lipoprotein, intermediate-density lipoprotein and LDL. It is concluded that endotoxin suppresses hepatic LDL receptor expression in vivo in rats.

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