scholarly journals Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice

2012 ◽  
Vol 302 (2) ◽  
pp. R244-R251 ◽  
Author(s):  
Frederique Yiannikouris ◽  
Michael Karounos ◽  
Richard Charnigo ◽  
Victoria L. English ◽  
Debra L. Rateri ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Blood Pressure Control ◽  
Fat Mass ◽  
Plasma Concentrations ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Fatty Acid Binding ◽  
Exon 2

Previous studies demonstrated that overexpression of angiotensinogen (AGT) in adipose tissue increased blood pressure. However, the contribution of endogenous AGT in adipocytes to the systemic renin-angiotensin system (RAS) and blood pressure control is undefined. To define a role of adipocyte-derived AGT, mice with loxP sites flanking exon 2 of the AGT gene ( Agt fl/fl) were bred to transgenic mice expressing Cre recombinase under the control of an adipocyte fatty acid-binding protein 4 promoter (aP2) promoter to generate mice with adipocyte AGT deficiency ( Agt aP2). AGT mRNA abundance in adipose tissue and AGT secretion from adipocytes were reduced markedly in adipose tissues of Agt aP2 mice. To determine the contribution of adipocyte-derived AGT to the systemic RAS and blood pressure control, mice were fed normal laboratory diet for 2 or 12 mo. In males and females of each genotype, body weight and fat mass increased with age. However, there was no effect of adipocyte AGT deficiency on body weight, fat mass, or adipocyte size. At 2 and 12 mo of age, mice with deficiency of AGT in adipocytes had reduced plasma concentrations of AGT (by 24–28%) compared with controls. Moreover, mice lacking AGT in adipocytes exhibited reduced systolic blood pressures compared with controls ( Agt fl/fl, 117 ± 2; Agt aP2, 110 ± 2 mmHg; P < 0.05). These results demonstrate that adipocyte-derived AGT contributes to the systemic RAS and blood pressure control.

Abstract P060: Angiotensin AT1A Receptors on Vasopressin-Expressing Cells are Dispensable for DOCA-salt Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jeremy A Sandgren ◽  
Danny W Linggonegoro ◽  
Kristin E Claflin ◽  
Nicole A Pearson ◽  
Gary L Pierce ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Specific Activity ◽  
Fluorescent Microscopy ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Fluorescent Reporter ◽  
Significant Difference ◽  
Low Renin Hypertension ◽  
Salt Hypertension

Increased blood pressure in the deoxycorticosterone acetate (DOCA)-salt model of low-renin hypertension is correlated with increased vasopressin (AVP) secretion, and is sensitive to inhibition of the brain renin-angiotensin system (RAS). Further, AVP-deficient Brattleboro rats are largely resistant to DOCA-salt hypertension. These findings lead us to hypothesize a role for AT1A receptors localized to AVP-expressing neurons in the control of AVP secretion, specifically in low-renin hypertension. Blood pressure was assessed via tail-cuff plesthysmography and total daily AVP secretion assessed via urine copeptin in mice with specific disruption of the AT1A gene in AVP-expressing cells (AVP-Cre x AT1Aflox/flox mice, “KO”) under both baseline and DOCA-salt treatment conditions. Specific activity of Cre-recombinase within the paraventricular and supraoptic nuclei of AVP-Cre transgenic mice was confirmed by fluorescent microscopy in brain sections from mice expressing a conditional fluorescent reporter (AVP-Cre x ROSA-stopflox-tdTomato mice). At baseline, AVP secretion (via urine copeptin) trended downward with large variation (control n=17, 363±182 vs KO n=5, 33±11 pg/day; p>0.05) but there was no significant difference in blood pressure (control n=27, 107±1.3 vs KO n=12, 111±2.2 mmHg; p>0.05) compared to littermate controls. In response to DOCA-salt, blood pressure (control n=23, +10.35±2.1 vs KO n=8, +12.91±2.0; p>0.05), urine output (control n=23, +12.65±0.8 vs KO n=9, +12.73±1.5 g/day; p>0.05), and fluid intake (control n=23, +16.17±1.3 vs KO n=9, +14.83±2.5 mL/day; p>0.05) increased normally in KO mice. Preliminary findings indicate normal or possibly exaggerated urine copeptin levels in KO mice following DOCA-salt, and an exaggerated AVP release in response to increasing serum osmolality. Collectively, these data suggest that AT1A receptors on AVP expressing cells are required to mediate baseline secretion of AVP, but that these receptors are dispensable for DOCA-salt mediated increases in circulating AVP and blood pressure.

Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension

2004 ◽  
Vol 287 (4) ◽  
pp. R943-R949 ◽  
Author(s):  
Carine M. Boustany ◽  
Kalyani Bharadwaj ◽  
Alan Daugherty ◽  
David R. Brown ◽  
David C. Randall ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Body Weight Gain ◽  
Plasma Concentrations ◽  
Renin Angiotensin System ◽  
Sprague Dawley ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood

In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is markedly expanded in obesity. This study evaluated changes in components of the adipose and systemic RAS in diet-induced obese hypertensive rats. RAS was quantified in adipose tissue and compared with primary sources for the circulating RAS. Male Sprague-Dawley rats were fed either a low-fat (LF; 11% kcal as fat) or moderately high-fat (32% kcal as fat) diet for 11 wk. After 8 wk, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on their body weight gain (body weight: OR, 566 ± 10; OP, 702 ± 20 g; P < 0.05). Mean arterial blood pressure was increased in OP rats (LF: 97 ± 2; OR: 97 ± 2; OP: 105 ± 1 mmHg; P < 0.05). Quantification of mRNA expression by real-time PCR demonstrated a selective increase (2-fold) in angiotensinogen gene expression in retroperitoneal adipose tissue from OP vs. OR and LF rats. Similarly, plasma angiotensinogen concentration was increased in OP rats (LF: 390 ± 48; OR: 355 ± 24; OP: 530 ± 22 ng/ml; P < 0.05). In contrast, other components of the RAS were not altered in OP rats. Marked increases in the plasma concentrations of angiotensin peptides were observed in OP rats (angiotensin II: LF: 95 ± 31; OR: 59 ± 20; OP: 295 ± 118 pg/ml; P < 0.05). These results demonstrate increased activity of the adipose and systemic RAS in obesity-related hypertension.

Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients

Cytokine ◽  
2010 ◽  
Vol 50 (3) ◽  
pp. 284-291 ◽  
Author(s):  
Dimas Ikeoka ◽  
Christoph Pachler ◽  
Stefan Korsatko ◽  
Julia K. Mader ◽  
Heinz Weinhandl ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Blood Pressure Control ◽  
Interleukin 6 ◽  
Subcutaneous Adipose Tissue ◽  
Pressure Control ◽  
Subcutaneous Adipose

Role of Vasopressin in Blood Pressure Control of Spontaneously Hypertensive Rats

1978 ◽  
Vol 55 (s4) ◽  
pp. 247s-250s ◽  
Author(s):  
Jan Möhring ◽  
Jacqueline Kintz ◽  
Josiane Schoun
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Spontaneously Hypertensive Rats ◽  
Salt Intake ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Salt Intake

1. The role of arginine—vasopressin (AVP) and of angiotensin in blood pressure control of spontaneously hypertensive rats (SH rats, stroke-prone strain) was studied. 2. In SH rats, which drank water or 1% NaCl, plasma AVP concentrations were elevated during the benign course of hypertension and increased further when the animals entered the malignant phase. Blood pressure correlated significantly with plasma AVP concentrations in SH rats on water, but not in SH rats on saline. 3. The injection of a specific AVP antiserum lowered blood pressure significantly in SH rats on water and in SH rats on saline. 4. When the correlation between blood pressure and plasma AVP of SH rats on water was compared with the respective correlation obtained during infusion of AVP into normotensive rats, a marked shift to the left became apparent, the factor of displacement amounting to more than 1000. 5. Saralasin did not affect blood pressure of SH rats on water, except for two rats with malignant hypertension. However, in SH rats on saline, saralasin lowered blood pressure significantly. 6. It is concluded that in SH rats AVP plays an important vasopressor role in blood pressure control and that sensitization to the vasopressor effect of AVP occurs in these animals. The renin—angiotensin system is significantly involved in blood pressure control of SH rats only when they are subjected to high salt intake.

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