Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction

2008 ◽  
Vol 294 (5) ◽  
pp. H2069-H2077 ◽  
Author(s):  
Vincent J. de Beer ◽  
Oana Sorop ◽  
Daniël A. Pijnappels ◽  
Dick H. Dekkers ◽  
Frans Boomsma ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cross Talk ◽  
Receptor Expression ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Coronary Resistance ◽  
Resistance Vessel ◽  
Coronary Vasodilator ◽  
Resistance Vessels

Several studies have indicated an interaction between the renin-angiotensin (ANG II) system and endothelin (ET) in the regulation of vascular tone. Previously, we have shown that both ET and ANG II exert a vasoconstrictor influence on the coronary resistance vessels of awake normal swine. Here, we investigated whether the interaction between ANG II and ET exists in the control of coronary resistance vessel tone at rest and during exercise using single and combined blockade of angiotensin type 1 (AT1) and ETA/ETB receptors. Since both circulating ANG II and ET levels are increased after myocardial infarction (MI), we investigated if the interaction between these systems is altered after MI. In awake healthy swine, coronary vasodilation in response to ETA/ETB receptor blockade in the presence of AT1 blockade was similar to vasodilation produced by ETA/ETB blockade under control conditions. In awake swine with a 2- to 3-wk-old MI, coronary vasodilator responses to individual AT1 and ETA/ETB receptor blockade were virtually abolished, despite similar coronary arteriolar AT1 and ETA receptor expression compared with normal swine. Unexpectedly, in the presence of AT1 blockade (which had no effect on circulating ET levels), ETA/ETB receptor blockade elicited a coronary vasodilator response. These findings suggest that in normal healthy swine the two vasoconstrictor systems contribute to coronary resistance vessel control in a linear additive manner, i.e., with negligible cross-talk. In contrast, in the remodeled myocardium, cross-talk between ANG II and ET emerges, resulting in nonlinear redundant control of coronary resistance vessel tone.

Hypertension in mice lacking the CXCR3 chemokine receptor

2009 ◽  
Vol 296 (4) ◽  
pp. F780-F789 ◽  
Author(s):  
Hsiang-Hao Hsu ◽  
Kerstin Duning ◽  
Hans Henning Meyer ◽  
Miriam Stölting ◽  
Thomas Weide ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Chemokine Receptor ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Ang Ii ◽  
Vascular Contractility ◽  
Resistance Vessels ◽  
M3 Receptor

The CXC chemokine receptor 3 (CXCR3) has been linked to autoimmune and inflammatory disease, allograft rejection, and ischemic nephropathy. CXCR3 is expressed on endothelial and smooth muscle cells. Although a recent study posited that antagonizing of CXCR3 function may reduce atherosclerosis, the role of CXCR3 in controlling physiological vascular functions remains unclear. This study demonstrates that disruption of CXCR3 leads to elevated mean arterial pressures in anesthetized and conscious mice, respectively. Stimulation of isolated resistance vessels with various vasoconstrictors showed increased contractibility in CXCR3−/− mice in response to angiotensin II (ANG II) and a decreased vasodilatation in response to acetylcholine (ACh). The increased contractibility was related to higher ANG II type 1 receptor (AT1R) expression, whereas the decreased vasodilatation was related to lower M3-ACh receptor expression in the mesenteric arteries of CXCR3−/− mice compared with wild-type mice. The vasodilatatory response to ACh could be antagonized by the nonselective ACh receptor antagonist atropine and the selective M3 receptor antagonist 4-DAMP, but not by M1, M2, and M4 receptor antagonists. Additionally, EMSA studies revealed that transcription factors SP-1 and EGR-1 interact as a complex with the murine AT1R promoter region. Furthermore, we could show increased expression of SP-1 in CXCR3−/− mice indicating an imbalanced SP-1 and EGR-1 complex formation which causes increased AT1R expression and hypertension. The data indicate that CXCR3 receptor is important in vascular contractility and hypertension, possibly through upregulated AT1R expression.

scholarly journals Angiotensin receptors alter myocardial infarction-induced remodeling of the guinea pig cardiac plexus

2015 ◽  
Vol 309 (2) ◽  
pp. R179-R188 ◽  
Author(s):  
Jean C. Hardwick ◽  
Shannon E. Ryan ◽  
Emily N. Powers ◽  
E. Marie Southerland ◽  
Jeffrey L. Ardell
Keyword(s):  
Myocardial Infarction ◽  
Guinea Pig ◽  
Neuronal Excitability ◽  
Synaptic Function ◽  
Receptor Expression ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Muscarinic Agonists ◽  
Neuronal Remodeling ◽  
Drug Treatments

Neurohumoral remodeling is fundamental to the evolution of heart disease. This study examined the effects of chronic treatment with an ACE inhibitor (captopril, 3 mg·kg−1·day−1), AT1 receptor antagonist (losartan, 3 mg·kg−1·day−1), or AT2 receptor agonist (CGP42112A, 0.14 mg·kg−1·day−1) on remodeling of the guinea pig intrinsic cardiac plexus following chronic myocardial infarction (MI). MI was surgically induced and animals recovered for 6 or 7 wk, with or without drug treatment. Intracellular voltage recordings from whole mounts of the cardiac plexus were used to monitor changes in neuronal responses to norepinephrine (NE), muscarinic agonists (bethanechol), or ANG II. MI produced an increase in neuronal excitability with NE and a loss of sensitivity to ANG II. MI animals treated with captopril exhibited increased neuronal excitability with NE application, while MI animals treated with CGP42112A did not. Losartan treatment of MI animals did not alter excitability with NE compared with untreated MIs, but these animals did show an enhanced synaptic efficacy. This effect on synaptic function was likely due to presynaptic AT1 receptors, since ANG II was able to reduce output to nerve fiber stimulation in control animals, and this effect was prevented by inclusion of losartan in the bath solution. Analysis of AT receptor expression by Western blot showed a decrease in both AT1 and AT2 receptors with MI that was reversed by all three drug treatments. These data indicate that neuronal remodeling of the guinea pig cardiac plexus following MI is mediated, in part, by activation of both AT1 and AT2 receptors.

scholarly journals Effects of Prehypertensive Losartan Treatment on Resistance Vessel Remodeling and Angiotensin II Type 1 Receptor Expression in Spontaneously Hypertensive Rats

2020 ◽  
Vol 33 (5) ◽  
pp. 471-471
Author(s):  
Ting-jun Wang ◽  
Wan-ru Chen ◽  
Xu Lin ◽  
Gui-li Lian ◽  
Chang-sheng Xu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Resistance Vessel ◽  
Spontaneously Hypertensive ◽  
Vessel Remodeling ◽  
Wistar Kyoto ◽  
Losartan Treatment

Abstract Background To study the effects of prehypertensive losartan treatment on blood pressure, resistance vessel remodeling, and angiotensin II type 1 receptor (AT1R) expression in adult spontaneously hypertensive rats (SHRs). Methods Four-week-old SHR and Wistar-Kyoto rats were randomly divided into losartan-treated and untreated groups. Losartan was administrated by gavage from 4 to 10 weeks old. Blood pressure was monitored by the tail-cuff method till 26 weeks old. The third grade mesenteric arteries were then isolated. Vessel structure, relaxation reactivity, angiotensin II type 1 receptor expression, and angiotensin II levels were analyzed. Results Losartan treatment from 4 to 10 weeks of age significantly lowered systolic blood pressure from 10 to 26 weeks in SHR. At 26 weeks old, wall thickness to lumen radius and wall area to lumen area of mesenteric arteries were significantly lower in losartan-treated than untreated SHR (P < 0.01). Maximum relaxation to acetylcholine and its pD2 were increased in losartan-treated compared to untreated SHR (P < 0.01). Angiotensin II type 1 receptor mRNA and protein levels were significantly reduced in losartan-treated SHR (P < 0.01). However, angiotensin II levels in plasma and mesenteric arteries of losartan-treated SHR were higher than those of untreated SHR (P < 0.05). Losartan treatment lowered systolic blood pressure in Wistar-Kyoto at the age of 10 weeks (P < 0.05), but had no significant effect on blood pressure after 14 weeks or mesenteric arteries at 26 weeks. Conclusions Blood pressure reduction induced by prehypertensive losartan treatment ameliorates resistance vessel remodeling and downregulates angiotensin II type 1 receptor expression in adult SHR.

Localization of Angiotensin II Type 1 receptor gene expression in rodent and human kidneys

2021 ◽  
Author(s):  
Julia Schrankl ◽  
Michaela Fuchs ◽  
Katharina Broeker ◽  
Christoph Daniel ◽  
Armin Kurtz ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Vascular System ◽  
Receptor Gene ◽  
Cell Types ◽  
Receptor Expression ◽  
Ang Ii ◽  
Comprehensive Overview ◽  
Different Cell Types

The kidneys are an important target for angiotensin II (ANG II). In the adult kidneys the effects of ANG II are mediated mainly by ANG II type 1 (AT1) receptors. AT1 receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT1 receptors, this study aimed to obtain a comprehensive overview about the localization of AT1 receptor expression in mouse, rat and human kidneys. Using the cell specific and high-resolution RNAscope technique, we performed colocalization studies with various cell markers to specifically discriminate between different segments of the tubular and vascular system. Overall we found a similar pattern of AT1 mRNA expression in mouse, rat and human kidneys. AT1 receptors were detected in mesangial cells and renin-producing cells. In addition, AT1 mRNA was found in interstitial cells of the cortex and outer medulla. In rodents, late afferent and early efferent arterioles expressed AT1 receptor mRNA, but larger vessels of the investigated species showed no AT1 expression. Tubular expression of AT1 mRNA was species-dependent with a strong expression in proximal tubules of mice while expression was undetectable in human tubular cells. These findings suggest that the (juxta)glomerular area and the tubulointerstitium are conserved expression sites for AT1 receptors across species and might present the main target sites for ANG II in adult human and rodent kidneys.

Cardiac hypertrophy is associated with altered thioredoxin and ASK-1 signaling in a mouse model of menopause

2008 ◽  
Vol 295 (4) ◽  
pp. H1481-H1488 ◽  
Author(s):  
Talin Ebrahimian ◽  
M. Ram Sairam ◽  
Ernesto L. Schiffrin ◽  
Rhian M. Touyz
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Receptor Expression ◽  
Ang Ii ◽  
Antioxidant Function ◽  
Endogenous Antioxidant

Oxidative stress is implicated in menopause-associated hypertension and cardiovascular disease. The role of antioxidants in this process is unclear. We questioned whether the downregulation of thioredoxin (TRX) is associated with oxidative stress and the development of hypertension and target-organ damage (cardiac hypertrophy) in a menopause model. TRX is an endogenous antioxidant that also interacts with signaling molecules, such as apoptosis signal-regulated kinase 1 (ASK-1), independently of its antioxidant function. Aged female wild-type (WT) and follitropin receptor knockout (FORKO) mice (20–24 wk), with hormonal imbalances, were studied. Mice were infused with ANG II (400 ng·kg−1·min−1; 14 days). Systolic blood pressure was increased by ANG II in WT (166 ± 8 vs. 121 ± 5 mmHg) and FORKO (176 ± 7 vs. 115 ± 5 mmHg; P < 0.0001; n = 9/group) mice. In ANG II-infused FORKO mice, cardiac mass was increased by 42% ( P < 0.001). This was associated with increased collagen content and augmented ERK1/2 phosphorylation (2-fold). Cardiac TRX expression and activity were decreased by ANG II in FORKO but not in WT ( P < 0.01) mice. ASK-1 expression, cleaved caspase III content, and Bax/Bcl-2 content were increased in ANG II-infused FORKO ( P < 0.05). ANG II had no effect on cardiac NAD(P)H oxidase activity or on O2•− levels in WT or FORKO. Cardiac ANG II type 1 receptor expression was similar in FORKO and WT. These findings indicate that in female FORKO, ANG II-induced cardiac hypertrophy and fibrosis are associated with the TRX downregulation and upregulation of ASK-1/caspase signaling. Our data suggest that in a model of menopause, protective actions of TRX may be blunted, which could contribute to cardiac remodeling independently of oxidative stress and hypertension.

scholarly journals Increased expression of glomerular AT1 receptors in rats with myocardial infarction

1998 ◽  
Vol 275 (4) ◽  
pp. H1247-H1253 ◽  
Author(s):  
Peter F. Mento ◽  
Mary E. Pica ◽  
Jim Hilepo ◽  
Jaime Chang ◽  
Larissa Hirsch ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Receptor Expression ◽  
Angiotensin Receptors ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Artery Ligation ◽  
Excretory Function ◽  
Renin Mrna

Rats with congestive heart failure demonstrate striking intrarenal vasoconstriction that contributes to reduced renal excretory function. We previously demonstrated that inhibition of angiotensin action reverses intrarenal vasoconstriction in rats 4–6 wk after coronary artery ligation. In the present study we tested the hypothesis that abnormalities in the expression and regulation of glomerular angiotensin receptors contribute to the intrarenal vasoconstriction. Because glomerular angiotensin type 1 (AT1) receptors normally downregulate in response to high local ANG II concentrations, we anticipated that glomerular AT1-receptor expression would be reduced in rats after myocardial infarction (MI). To our surprise, the density of glomerular AT1receptors was nearly double (97% increase, P < 0.002) that of controls, indicating an acquired abnormality in angiotensin receptor regulation. This was specific for renal glomeruli, because the density of angiotensin receptors on renal vasculature was decreased in rats after MI compared with normal controls. Glomerular AT1-receptor expression was downregulated by an acute pharmacological infusion of ANG II and upregulated by acute angiotensin-converting enzyme inhibition to a similar extent in MI and control rats. Renal cortical mRNA expression showed an increase in the renin mRNA-to-actin ratio and angiotensinogen-to-actin ratio, indicating stimulation of the intrarenal angiotensin system in rats after MI. The data indicate a specific dysregulation of AT1receptors in glomeruli but not blood vessels after MI.

Angiotensin II mediates uterine vasoconstriction through α-stimulation

2004 ◽  
Vol 287 (1) ◽  
pp. H126-H134 ◽  
Author(s):  
Blair E. Cox ◽  
Timothy A. Roy ◽  
Charles R. Rosenfeld
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Pressor Responses ◽  
Adrenergic Activation

Intravenous angiotensin II (ANG II) increases uterine vascular resistance (UVR), whereas uterine intra-arterial infusions do not. Type 2 ANG II (AT2) receptors predominate in uterine vascular smooth muscle; this may reflect involvement of systemic type 1 ANG II (AT1) receptor-mediated α-adrenergic activation. To examine this, we compared systemic pressor and UVR responses to intravenous phenylephrine and ANG II without and with systemic or uterine α-receptor blockade and in the absence or presence of AT1 receptor blockade in pregnant and nonpregnant ewes. Systemic α-receptor blockade inhibited phenylephrine-mediated increases in mean arterial pressure (MAP) and UVR, whereas uterine α-receptor blockade alone did not alter pressor responses and resulted in proportionate increases in UVR and MAP. Although neither systemic nor uterine α-receptor blockade affected ANG II-mediated pressor responses, UVR responses decreased >65% and also were proportionate to increases in MAP. Systemic AT1 receptor blockade inhibited all responses to intravenous ANG II. In contrast, uterine AT1 receptor blockade + systemic α-receptor blockade resulted in persistent proportionate increases in MAP and UVR. Uterine AT2 receptor blockade had no effects. We have shown that ANG II-mediated pressor responses reflect activation of systemic vascular AT1 receptors, whereas increases in UVR reflect AT1 receptor-mediated release of an α-agonist and uterine autoregulatory responses.

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