Glucocorticoids potentiate central actions of angiotensin to increase arterial pressure

2001 ◽  
Vol 280 (6) ◽  
pp. R1719-R1726 ◽  
Author(s):  
Deborah A. Scheuer ◽  
Andrea G. Bechtold
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Guide Cannula ◽  
Intravenous Injections ◽  
Sprague Dawley Rats ◽  
And Control

Experiments were performed to determine if glucocorticoids potentiate central hypertensive actions of ANG II. Male Sprague-Dawley rats were treated for 3 days to 3 wk with corticosterone (Cort). Experiments were performed in conscious rats that had previously been instrumented with arterial and venous catheters and an intracerebroventricular guide cannula in a lateral ventricle. Baseline arterial pressure (AP) was greater in Cort-treated rats than in control rats (119 ± 2 vs. 107 ± 1 mmHg, P < 0.01). Microinjection of ANG II intracerebroventricularly produced a significantly larger increase in AP in Cort-treated rats than in control rats. For example, at 30 ng ANG II, AP increased by 23 ± 1 and 16 ± 2 mmHg in Cort-treated and control rats, respectively ( P < 0.01). Microinjection of an angiotensin type 1 receptor antagonist significantly decreased AP (−6 ± 2 mmHg) and heart rate (−26 ± 7 beats/min) in Cort-treated but not control rats. Increases in AP produced by intravenous administration of ANG II were not different between control and Cort-treated rats. Intravenous injections of ANG II antagonist had no significant effects on mean AP or heart rate in control or Cort-treated rats. Therefore, a sustained increase in plasma Cort augments the central pressor effects of ANG II without altering the pressor response to peripheral administration of the hormone.

scholarly journals AT1 receptors in the subfornical organ modulate arterial pressure and the baroreflex in two-kidney, one-clip hypertensive rats

2019 ◽  
Vol 316 (2) ◽  
pp. R172-R185 ◽  
Author(s):  
Noreen F. Rossi ◽  
Zachary Zenner ◽  
Arun K. Rishi ◽  
Edi Levi ◽  
Maria Maliszewska-Scislo
Keyword(s):  
Arterial Pressure ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Sprague Dawley Rats ◽  
Radio Transmitters ◽  
Vascular Catheters

The subfornical organ (SFO), a forebrain circumventricular organ that lies outside the blood-brain barrier, has been implicated in arterial pressure and baroreflex responses to angiotensin II (ANG II). We tested whether pharmacological inhibition or selective silencing of SFO ANG II type 1 receptors (AT1R) of two-kidney, one-clip rats with elevated plasma ANG II decreases resting arterial pressure and renal sympathetic nerve activity (RSNA) and/or modulates arterial baroreflex responses of heart rate (HR) and RSNA. Male Sprague-Dawley rats underwent renal artery clipping [2-kidney, 1-clip (2K,1C)] or sham clipping (sham). After 6 wk, conscious rats instrumented with vascular catheters, renal nerve electrodes, and a cannula directed to the SFO were studied. In another set of experiments, rats were instrumented with hemodynamic and nerve radio transmitters and injected with scrambled RNA or silencing RNA targeted against AT1R. Mean arterial pressure (MAP) was significantly higher in 2K,1C rats. Acute SFO injection with the AT1R inhibitor losartan did not change MAP in sham or 2K,1C rats. Baroreflex curves of HR and RSNA were shifted rightward in 2K,1C rats. Losartan exerted no effect. SFO AT1R knockdown did not influence MAP in sham rats but decreased MAP in 2K,1C rats, despite no change in plasma ANG II or resting RSNA. AT1R knockdown prevented the reduction in maximum gain and slope of baroreflex responses of HR and RSNA; the reduced RSNA response to baroreceptor unloading was partially restored in 2K,1C rats. These findings show that AT1R activation within the SFO contributes to hypertension and baroreflex dysfunction in 2K,1C rats and highlight the temporal requirement for reversal of these effects.

scholarly journals Down-regulation of Brain Gα12 attenuates Angiotensin II Dependent Hypertension

2019 ◽  
Author(s):  
Juan Gao ◽  
Ian Denys ◽  
Amir Shahien ◽  
Jane Sutphen ◽  
Daniel R Kapusta
Keyword(s):  
Angiotensin Ii ◽  
Baroreflex Sensitivity ◽  
Pressor Response ◽  
Ang Ii ◽  
Protein Signaling ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Chronic Infusion

Abstract Background Angiotensin II (Ang II) activates central Angiotensin II type 1 receptors (AT1R) to increase blood pressure (BP) via multiple pathways. However, whether central Gα proteins contribute to Ang II induced hypertension remains unknown. We hypothesized that AT1R couple with Gα12 and/or Gαq to produce sympatho-excitation and increase BP and downregulation of these Gα subunit proteins will attenuate Ang II dependent hypertension. Methods & Results After chronic infusion of Ang II (s.c. 350 ng/kg/min) or vehicle for 2-weeks, Ang II evoked an increase in Gα12 expression, but not Gαq in the RVLM of Sprague-Dawley rats. In other studies, rats that received Ang II or vehicle infusion s.c. were simultaneously infused i.c.v. with a scrambled (SCR) or Gα12 oligodeoxynucleotide (ODN; 50 μg/day). Central Gα12 ODN infusion lowered mean BP in Ang II infused rats compared with SCR ODN infusion (14- day peak; 133 ± 12 vs 176 ± 11 mmHg). Compared to the SCR ODN group, Ang II infused rats that received i.c.v. Gα12 ODN showed a greater increase in heart rate to atropine, an attenuated reduction in BP to chlorisondamine, and an improved baroreflex sensitivity. In addition, central Gα12 and Gαq ODN pretreatment blunted the pressor response to an acute i.c.v. injection of Ang II (i.c.v., 200 ng). Conclusions These findings suggest that central Gα12 protein signaling pathways play an important role in the development of chronic AngII-dependent hypertension in rats.

Changes in angiotensin type 1 receptor binding and angiotensin-induced pressor responses in the rostral ventrolateral medulla of angiotensinogen knockout mice

2010 ◽  
Vol 298 (2) ◽  
pp. R411-R418 ◽  
Author(s):  
Daian Chen ◽  
Lisa Hazelwood ◽  
Lesley L. Walker ◽  
Brian J. Oldfield ◽  
Michael J. McKinley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Receptor Binding ◽  
Knockout Mice ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Wild Type ◽  
Intravenous Injections ◽  
Angiotensin Type

ANG II, the main circulating effector hormone of the renin-angiotensin system, is produced by enzymatic cleavage of angiotensinogen. The present study aimed to examine whether targeted deletion of the angiotensinogen gene ( Agt) altered brain ANG II receptor density or responsiveness to ANG II. In vitro autoradiography was used to examine the distribution and density of angiotensin type 1 (AT1) and type 2 receptors. In most brain regions, the distribution and density of angiotensin receptors were similar in brains of Agt knockout mice ( Agt −/− ) and wild-type mice. In Agt −/− mice, a small increase in AT1 receptor binding was observed in the rostral ventrolateral medulla (RVLM), a region that plays a critical role in blood pressure regulation. To examine whether Agt −/− mice showed altered responses to ANG II, blood pressure responses to intravenous injection (0.01–0.1 μg/kg) or RVLM microinjection (50 pmol in 50 nl) of ANG II were recorded in anesthetized Agt −/− and wild-type mice. Intravenous injections of phenylephrine (4 μg/kg and 2 μg/kg) were also made in both groups. The magnitude of the pressor response to intravenous injections of ANG II or phenylephrine was not different between Agt −/− and wild-type mice. Microinjection of ANG II into the RVLM induced a pressor response, which was significantly smaller in Agt −/− compared with wild-type mice (+10 ± 1 vs. +23 ± 4 mmHg, respectively, P = 0.004). Microinjection of glutamate into the RVLM (100 pmol in 10 nl) produced a robust pressor response, which was not different between Agt −/− and wild-type mice. A diminished response to ANG II microinjection in the RVLM of Agt −/− mice, despite an increased density of AT1 receptors suggests that signal transduction pathways may be altered in RVLM neurons of Agt −/− mice, resulting in attenuated cellular excitation.

Dietary obesity and weight cycling in rats: a model of stress-induced hypertension?

1991 ◽  
Vol 261 (4) ◽  
pp. R848-R857 ◽  
Author(s):  
R. J. Contreras ◽  
S. King ◽  
L. Rives ◽  
A. Williams ◽  
T. Wattleton
Keyword(s):  
Heart Rate ◽  
Sodium Excretion ◽  
Mild Hypertension ◽  
Weight Cycling ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sweetened Condensed Milk ◽  
Condensed Milk ◽  
Sprague Dawley Rats ◽  
Dietary Obesity

The present study was designed to reproduce the mild hypertension seen in dietary obese weight-cycled rats [P. Ernsberger and D. O. Nelson. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R47-R55, 1988] and determine whether this mild hypertension was associated with changes in sodium excretion and pressor responsiveness to angiotensin II (ANG II). Male Sprague-Dawley rats were fed pelleted chow (Pellet group) or chow plus sweetened condensed milk (Milk group) or were exposed to four cycles of a 4-day fast alternated with 2 wk of refeeding of pelleted chow and sweetened condensed milk (Cycled group). Blood pressure and heart rate were measured by tail cuff at the onset and last day of each fast and after 3 days of refeeding. During fasting, urine sodium excretion was measured. Mean arterial pressure and heart rate responses to intravenous administration of ANG II (40, 80, and 120 ng/kg), metoprolol (1 mg/kg), and methyl scopolamine (2 mg/kg) were obtained from the femoral artery in awake unrestrained rats. Weight cycling did not lead to mild hypertension or increased bradycardic response to sympathetic blockade with metoprolol. ANG II-elicited pressor responses were similar for Pellet, Milk, and Cycled groups. Sodium excretion did not change with fasting. Mild hypertension developed when obese weight-cycled rats were housed together in groups and not when housed individually. Our preliminary data are consistent with the notion that stress associated with group housing may be a factor in the mild hypertension of obese weight-cycled rats.

Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen

2007 ◽  
Vol 293 (1) ◽  
pp. H590-H598 ◽  
Author(s):  
Eduard I. Dedkov ◽  
Wei Zheng ◽  
Lance P. Christensen ◽  
Robert M. Weiss ◽  
Florence Mahlberg-Gaudin ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Perfusion ◽  
Transforming Growth Factor ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Coronary Reserve ◽  
Osmotic Pumps ◽  
Sprague Dawley Rats

We tested the hypothesis that chronically reducing the heart rate in infarcted middle-aged rats using ivabradine (IVA) would induce arteriolar growth and attenuate perivascular collagen and, thereby, improve maximal perfusion and coronary reserve in the surviving myocardium. Myocardial infarction (MI) was induced in 12-mo-old male Sprague-Dawley rats, which were then treated with either IVA (10.5 mg·kg−1·day−1; MI + IVA) or placebo (MI) via intraperitoneal osmotic pumps for 4 wk. Four weeks of IVA treatment limited the increase in left ventricular end-diastolic pressure and the decrease in ejection fraction but did not affect the size of the infarct, the magnitude of myocyte hypertrophy, or the degree of arteriolar and capillary growth. However, treatment reduced interstitial and periarteriolar collagen in the surviving myocardium of MI + IVA rats. The reduced periarteriolar collagen content was associated with improvement in maximal myocardial perfusion and coronary reserve. Although the rates of proliferation of periarteriolar fibroblasts were similar in the MI and MI + IVA groups, the expression levels of the AT1 receptor and transforming growth factor (TGF)-β1 in the myocardium, as well as the plasma level of the ANG II peptide, were lower in treated rats 14 days after MI. Therefore, our data reveal that improved maximal myocardial perfusion and coronary reserve in MI + IVA rats are most likely the result of reduced periarteriolar collagen rather than enhanced arteriolar growth.

scholarly journals Cooling-Evoked Hemodynamic Perturbations Facilitate Sympathetic Activity with Subsequent Myogenic Vascular Oscillations via Alpha2-Adrenergic Receptors

2017 ◽  
pp. 449-457 ◽  
Author(s):  
Y.-H. LIN ◽  
Y.-P. LIU ◽  
Y.-C. LIN ◽  
P.-L. LEE ◽  
C.-S. TUNG
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Response ◽  
Low Frequency ◽  
Power Spectral Analysis ◽  
Sprague Dawley ◽  
Cold Stimulation ◽  
Very Low Frequency ◽  
Power Spectral ◽  
Sprague Dawley Rats

This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexame-thonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethi-dine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge.

Effects of naloxone on renin and pressor responses to acute renal hypotension in rats.

1990 ◽  
Vol 259 (3) ◽  
pp. E432
Author(s):  
C J Weaver ◽  
M D Johnson
Keyword(s):  
Arterial Pressure ◽  
Abdominal Aorta ◽  
Pressor Response ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Opiate Antagonist ◽  
Sprague Dawley ◽  
Aortic Constriction ◽  
Sprague Dawley Rats ◽  
Pressor Responses

Reduction of renal perfusion is followed by increases in plasma renin activity (PRA) and arterial pressure. The present experiments were designed to determine if an opiate antagonist would alter pressor or renin responses to acute reduction of renal arterial pressure (RAP) in anesthetized rats. Male Sprague-Dawley rats were anesthetized with Inactin, and an adjustable constrictor device was placed around the abdominal aorta proximal to the renal arteries. One-half of the animals were pretreated with the opiate antagonist naloxone (2 mg/kg iv), and the other one-half were pretreated with saline vehicle. The abdominal aorta was then constricted to reduce RAP by 25% (measured as femoral arterial pressure) in one-half of the animals in each pretreatment group. Compared with vehicle pretreatment, naloxone pretreatment did not alter the PRA response to aortic constriction; however, naloxone did attenuate the pressor response. We conclude that 1) the PRA response to acute reduction of renal arterial pressure is not dependent on an opiate mechanism in the rat, and 2) attenuation of the pressor response to aortic constriction by naloxone in intact rats is not secondary to a suppression of the PRA response.

Effect of circulating vasopressin on arterial pressure regulation in rats

1989 ◽  
Vol 257 (1) ◽  
pp. H209-H218 ◽  
Author(s):  
C. M. Pawloski ◽  
N. M. Eicker ◽  
L. M. Ball ◽  
M. L. Mangiapane ◽  
G. D. Fink
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Body Fluid ◽  
Area Postrema ◽  
Sodium Intake ◽  
Blood Levels ◽  
Fluid Composition ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Autonomic Cardiovascular Control

It has been hypothesized that moderately increased blood levels of arginine vasopressin (AVP) contribute to the development and/or maintenance of hypertension. In this study, male Sprague-Dawley rats on a fixed 1 meq daily sodium intake received 10-day intravenous infusions of 0.2 and 2.0 ng.kg-1.min-1 AVP. The higher infusion rate was above the acute vasoconstrictor threshold for AVP administration and also produced a maximal antidiuretic effect. During chronic AVP administration, however, daily mean arterial pressure, heart rate, and body fluid composition were not changed, despite a maintained antidiuresis. To test the hypothesis that circulating AVP failed to cause hypertension as a result of sensitization of the baroreflex or a direct sympathoinhibitory effect of the peptide, additional experiments were performed in rats subjected to sinoaortic denervation (SAD) or ablation of the area postrema (APX). Infusion of AVP for 10 days into SAD or APX rats caused a sustained antidiuresis but did not change arterial pressure, heart rate, or body fluid composition. In all groups of rats, the depressor response to ganglionic blockade (20 mg/kg hexamethonium) was used to estimate the autonomic component of resting arterial pressure; no change in autonomic cardiovascular control was found using this method in any of the groups during AVP infusion. Long-term elevation of plasma AVP in rats, therefore, does not cause hypertension or significantly affect autonomic regulation of arterial pressure.

scholarly journals Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

2006 ◽  
Vol 290 (4) ◽  
pp. R1003-R1011 ◽  
Author(s):  
Andrea G. Bechtold ◽  
Deborah A. Scheuer
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Logistic Function ◽  
Receptor Expression ◽  
Arterial Baroreflex ◽  
Sprague Dawley ◽  
Baroreflex Control ◽  
Sprague Dawley Rats ◽  
Corticosteroid Receptor ◽  
Dorsal Hindbrain

Systemic corticosterone (Cort) modulates arterial baroreflex control of both heart rate and renal sympathetic nerve activity. Because baroreceptor afferents terminate in the dorsal hindbrain (DHB), an area with dense corticosteroid receptor expression, we tested the hypothesis that prolonged activation of DHB Cort receptors increases the midpoint and reduces the gain of arterial baroreflex control of heart rate in conscious rats. Small (3–4 mg) pellets of Cort (DHB Cort) or Silastic (DHB Sham) were placed on the surface of the DHB, or Cort was administered systemically by placing a Cort pellet on the surface of the dura (Dura Cort). Baroreflex control of heart rate was determined in conscious male Sprague Dawley rats on each of 4 days after initiation of treatment. Plots of arterial pressure vs. heart rate were analyzed using a four-parameter logistic function. After 3 days of treatment, the arterial pressure midpoint for baroreflex control of heart rate was increased in DHB Cort rats (123 ± 2 mmHg) relative to both DHB Sham (108 ± 3 mmHg) and Dura Cort rats (109 ± 2 mmHg, P < 0.05). On day 4, baseline arterial pressure was greater in DHB Cort (112 ± 2 mmHg) compared with DHB Sham (105 ± 2 mmHg) and Dura Cort animals (106 ± 2 mmHg, P < 0.05), and the arterial pressure midpoint was significantly greater than mean arterial pressure in the DHB Cort group only. Also on day 4, maximum baroreflex gain was reduced in DHB Cort (2.72 ± 0.12 beats·min−1·mmHg−1) relative to DHB Sham and Dura Cort rats (3.51 ± 0.28 and 3.37 ± 0.27 beats·min−1·mmHg−1, P < 0.05). We conclude that Cort acts in the DHB to increase the midpoint and reduce the gain of the heart rate baroreflex function.

Neuropeptide action in nucleus tractus solitarius: angiotensin specificity and hypertensive rats

1985 ◽  
Vol 249 (3) ◽  
pp. R341-R347 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Heart Rate ◽  
Nucleus Tractus Solitarius ◽  
Dose Range ◽  
Cardiovascular Effects ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto

We have reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius of urethan-anesthetized normotensive rats produces an increase in mean arterial pressure (MAP) over the dose range 50-500 pmol. The effect in spontaneously hypertensive rats (SHR) is now reported. Over the range 100-500 pmol SHR exhibit increases in MAP and heart rate greater than Wistar-Kyoto or Sprague-Dawley rats. SHR did not exhibit exaggerated responses to intravenous phenylephrine, suggesting a central site of increased responsiveness to ANG II. We also found depressor effects in Sprague-Dawley at lower doses (0.1 and 1 pmol). The decreases in MAP were extremely variable and not dose related. A selected dose of additional neuropeptides identified in the NTS was tested. Somatostatin, bradykinin, and vasoactive intestinal peptide (0.5 nmol) were without cardiovascular effects. Oxytocin and vasopressin, however, produced significant increases in MAP. Substance P produced a very small but significant increase in heart rate and MAP. Interaction between the vasopressin and ANG II pressor effects was studied, and each proved to be independent.

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