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Biomedical subjects

Lisa A Cassis

Publications and source records attributed to Lisa A Cassis.

At least 19 recordsLinked to original sources
PubMed2007

Angiotensin II increases adipose angiotensinogen expression.

In addition to the well-defined contribution of the liver, adipose tissue has been recognized as an important source of angiotensinogen (AGT). The purpose of this study was to define the angiotensin II (ANG II) receptors involved in regulation of adipose AGT and the relationship of this control to systemic AGT and/or angiotensin peptide concentrations. In LDL receptor-deficient (LDLR(-/-)) male mice, adipose mRNA abundance of AGT was 68% of that in liver, and adipose mRNA abundance of the angiotensin type 1a (AT(1a)) receptor (AT(1a)R) was 38% of that in liver, whereas mRNA abundance of the angiotensin type 2 (AT(2)) receptor (AT(2)R) was 57% greater in adipose tissue than in liver. AGT and angiotensin peptide concentrations were decreased in plasma of AT(1a)R-deficient (AT(1a)R(-/-)) mice and were paralleled by reductions in AGT expression in liver. In contrast, adipose AGT mRNA abundance was unaltered in AT(1a)R(-/-) mice. AT(2)R(-/-) mice exhibited elevated plasma angiotensin peptide concentrations and marked elevations in adipose AGT and AT(1a)R mRNA abundance. Increases in adipose AGT mRNA abundance in AT(2)R(-/-) mice were abolished by losartan. In contrast, liver AGT and AT(1a)R mRNA abundance were unaltered in AT(2)R(-/-) mice. Infusion of ANG II for 28 days into LDLR(-/-) mice markedly increased adipose AGT and AT(1a)R mRNA but did not alter liver AGT and AT(1a)R mRNA. These results demonstrate that differential mRNA abundance of AT(1a)/AT(2) receptors in adipose tissue vs. liver contributes to tissue-specific ANG II-mediated regulation of AGT. Chronic infusion of ANG II robustly stimulated AT(1a)R and AGT mRNA abundance in adipose tissue, suggesting that adipose tissue serves as a primary contributor to the activated systemic renin-angiotensin system.

Adipose Tissue↗
PubMed2006

Bone marrow transplantation reveals that recipient AT1a receptors are required to initiate angiotensin II-induced atherosclerosis and aneurysms.

OBJECTIVE: Angiotensin II (AngII) infusion into hypercholesterolemic mice accelerates atherosclerosis and promotes formation of abdominal aortic aneurysms (AAAs). The purpose of this study was to define whether AngII interacts with receptors on infiltrating versus resident cells in promoting vascular pathologies. METHODS AND RESULTS: Male LDL receptor -/- mice, that were either AT1a receptor +/+ or -/-, were fed a fat enriched diet and infused with either saline or AngII. AngII-induced augmentation of atherosclerosis and formation of AAAs was ablated in AT1a receptor -/- mice. Bone marrow transplantation studies were performed to determine the role of AT1a receptors expressed on infiltrating cells. AT1a receptor +/+ and -/- mice were irradiated and repopulated with bone marrow-derived stem cells of either genotype. These 4 groups of chimeric mice were infused with either saline or AngII. Repopulation of irradiated AT1a receptor +/+ mice with -/- bone marrow-derived cells resulted in modest reductions in AngII-induced atherosclerosis. Unexpectedly, AT1a receptor-deficient recipient mice were dramatically protected from AngII-induced vascular pathologies, irrespective of donor genotype. CONCLUSIONS: AngII promotes vascular pathology via AT1a receptors. AT1a receptors expressed on infiltrating cells exert modest regulation of AngII-induced atherosclerosis. However, the presence of this receptor in resident tissue is required for the initiation of AngII-induced atherosclerosis and AAAs.

Aneurysm↗
PubMed2006

Deletion of p47phox attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient mice.

BACKGROUND: Angiotensin II (Ang II) contributes to vascular pathology in part by stimulating NADPH oxidase activity, leading to increased formation of superoxide (O2-). We reported that O2- levels, NADPH oxidase activity, and expression of the p47phox subunit of NADPH oxidase are increased in human abdominal aortic aneurysms (AAAs). Here, we tested the hypothesis that deletion of p47phox will attenuate oxidative stress and AAA formation in Ang II-infused apoE-/- mice. METHODS AND RESULTS: Male apoE-/- and apoE-/-p47phox-/- mice received saline or Ang II (1000 ng x kg(-1) x min(-1)) infusion for 28 days, after which abdominal aortic weight and maximal diameter were determined. Aortic tissues and blood were examined for parameters of aneurysmal disease and oxidative stress. Ang II infusion induced AAAs in 90% of apoE-/- versus 16% of apo-/-p47phox-/- mice (P < 0.05). Abdominal aortic weight (14.1 +/- 3.2 versus 35.6 +/- 9.0 mg), maximal aortic diameter (1.5 +/- 0.2 versus 2.4 +/- 0.4 mm), aortic NADPH oxidase activity, and parameters of oxidative stress were reduced in apoE-/-p47phox-/- mice compared with apoE-/- mice (P < 0.05). In addition, aortic macrophage infiltration and matrix metalloproteinase-2 activity were reduced in apoE-/-p47phox-/- mice compared with apoE-/- mice. Deletion of p47phox attenuated the pressor response to Ang II; however, coinfusion of phenylephrine with Ang II, which restored the Ang II pressor response, did not alter the protective effects of p47phox deletion on AAA formation. CONCLUSIONS: Deletion of p47phox attenuates Ang II-induced AAA formation in apoE-/- mice, suggesting that NADPH oxidase plays a critical role in AAA formation in this model.

Adrenergic alpha-Agonists↗
PubMed2006

Empirical and theoretical analysis of the extremely low frequency arterial blood pressure power spectrum in unanesthetized rat.

The slope of the log of power versus the log of frequency in the arterial blood pressure (BP) power spectrum is classically considered constant over the low-frequency range (i.e., "fractal" behavior), and is quantified by beta in the relationship "1/f(beta)." In practice, the fractal range cannot extend to indefinitely low frequencies, but factor(s) that terminate this behavior, and determine beta, are unclear. We present 1) data in rats (n = 8) that reveal an extremely low frequency spectral region (0.083-1 cycle/h), where beta approaches 0 (i.e., the "shoulder"); and 2) a model that 1) predicts realistic values of beta within that range of the spectrum that conforms to fractal dynamics (approximately 1-60 cycles/h), 2) offers an explanation for the shoulder, and 3) predicts that the "successive difference" in mean BP (mBP) is an important parameter of circulatory function. We recorded BP for up to 16 days. The absolute difference between successive mBP samples at 0.1 Hz (the successive difference, or Delta) was 1.87 +/- 0.21 mmHg (means +/- SD). We calculated beta for three frequency ranges: 1) 0.083-1; 2) 1-6; and 3) 6-60 cycles/h. The beta for all three regions differed (P < 0.01). For the two higher frequency ranges, beta indicated a fractal relationship (beta(6-60/h) = 1.27 +/- 0.01; beta(1-6/h) = 1.80 +/- 0.16). Conversely, the slope of the lowest frequency region (i.e., the shoulder) was nearly flat (beta(0.083-1 /h) = 0.32 +/- 0.28). We simulated the BP time series as a random walk about 100 mmHg with ranges above and below of 10, 30, and 50 mmHg and with Delta from 0.5 to 2.5. The spectrum for the conditions mimicking actual BP time series (i.e., range, 85-115 mmHg; Delta, 2.00) resembled the observed spectra, with beta in the lowest frequency range = 0.207 and fractal-like behavior in the two higher frequency ranges (beta = 1.707 and 2.057). We suggest that the combined actions of mechanisms limiting the excursion of arterial BP produce the shoulder in the spectrum and that Delta contributes to determining beta.

Animals↗
PubMed2006

Role of the renin-angiotensin system in the development of abdominal aortic aneurysms in animals and humans.

The mediators for the initiation, progression, and rupture of abdominal aortic aneurysms (AAAs) have not been defined. Recent evidence has demonstrated that chronic infusion of angiotensin II via subcutaneously placed osmotic pumps can reproducibly form AAAs in mice. The evolution of AngII-induced AAAs in these mice is complex. Rapid medial macrophage accumulation precedes transmedial breaks and large lumen expansion, which are restricted to the suprarenal aorta. After this initial phase, there is a more gradual rate of lumen expansion that is progressive with continued AngII exposure. There is extensive aortic remodeling during this gradual expansion phase. An initial prominent thrombus gradually resolves and is replaced by fibrous tissue containing several types of inflammatory cells. At prolonged intervals of AngII infusion, internal aortic diameters of the suprarenal aorta can increase up to fourfold compared to the same region in saline-infused mice. The extrapolation of these data in mice to the development of human AAAs remains to be determined. However, there are a considerable number of drugs available to potentially test the efficacy of inhibiting the renin-angiotensin system on the progression of the human disease.

Angiotensin II↗
PubMed2005

Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.

BACKGROUND: Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E-deficient mice. METHODS AND RESULTS: Six-month-old male apolipoprotein E-deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure. CONCLUSIONS: Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II-driven AAA formation in hyperlipidemic mice.

Angiotensin II↗
PubMed2005

AT1-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity.

Previous studies in our laboratory demonstrated that rats exhibiting obesity in response to a moderately high-fat (MHF) diet developed hypertension associated with activation of the local and systemic renin-angiotensin system. In this study, we examined the effect of the angiotensin type 1 (AT(1))-receptor antagonist, losartan, on blood pressure in obesity-prone (OP) and obesity-resistant (OR) rats fed a MHF diet. Using telemetry monitoring, we characterized the evolution of blood pressure elevations during the development of obesity. Male Sprague-Dawley rats were implanted with telemetry transducers for chronic monitoring of blood pressure, and baseline measurements were obtained. Rats were then switched to the MHF diet (32% kcal as fat) and were segregated into OP and OR groups at week 5. At week 9 on the MHF diet, OP rats exhibited significantly greater 24-h mean arterial blood pressure compared with OR rats (OP: 105 +/- 4 mmHg, OR: 96 +/- 2 mmHg; P < 0.05). Elevations in blood pressure in OP rats were manifest as an increase in systolic pressure. Administration of losartan to all rats at week 9 resulted in a reduction in blood pressure; however, losartan had the greatest effect in OP rats (percent decrease in mean arterial pressure by losartan; OP: 19 +/- 4, OR: 10 +/- 2%; P < 0.05). These results demonstrate that elevations in blood pressure occur subsequent to established obesity in rats fed a high-fat diet. Moreover, these results demonstrate the ability of losartan to reverse the blood pressure increase from diet-induced obesity, supporting a primary role for the renin-angiotensin system in obesity-associated hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Aldosterone does not mediate angiotensin II-induced atherosclerosis and abdominal aortic aneurysms.

We have demonstrated previously that infusion of angiotensin II (AngII) into hyperlipidemic mice augments atherosclerosis and results in the formation of abdominal aortic aneurysms (AAA). The purpose of this study was to determine the role of aldosterone in these AngII-induced vascular pathologies. Male apolipoprotein E-/- (apoE) mice were infused with either vehicle or aldosterone (50 or 200 ng kg(-1) min(-1)). Arterial blood pressure was determined throughout the study and serum lipid concentrations and vascular pathology were quantified after 28 days of infusion. Infusion of aldosterone did not influence body weight or serum cholesterol concentrations. Kidney weight was increased dose-dependently by aldosterone infusion. Systolic blood pressure was not significantly altered by aldosterone. Plasma aldosterone concentrations were increased dose-dependently by infusion of aldosterone. However, there was no effect of aldosterone on the extent of atherosclerosis and AAAs were not formed. Implantation of pellets containing spironolactone (16 mg kg(-1) day(-1)) in AngII-infused apoE-/- mice (1000 ng kg(-1) min(-1)) had no effect on AngII-induced elevations in blood pressure. Plasma aldosterone concentration was not influenced by coadministration of spironolactone with AngII. Spironolactone administration did not influence the extent of atherosclerosis. Moreover, spironolactone had no significant effect on AngII-induced AAA (incidence of AAA formation: 80 versus 70% for vehicle versus spironolactone, respectively; not significant). These studies demonstrate that the AngII-induced vascular pathologies of atherosclerosis and AAA formation are not mediated through aldosterone.

Aldosterone↗
PubMed2004

Hypercholesterolemia stimulates angiotensin peptide synthesis and contributes to atherosclerosis through the AT1A receptor.

BACKGROUND: Hypercholesterolemia-induced atherosclerosis is attenuated by either pharmacological antagonism of AT1 receptors or AT1A receptor deficiency. However, the mechanism underlying the pronounced responses to angiotensin II (Ang II) antagonism has not been determined. We hypothesized that hypercholesterolemia stimulates the production of angiotensin peptides to provide a rationale for the profound effect of AT1A receptor deficiency on atherogenesis. METHODS AND RESULTS: Atherosclerotic lesions were analyzed in LDL receptor-deficient mice. Immunocytochemical analysis demonstrated that atherosclerotic lesions contained all the components of the conventional pathway for Ang II synthesis. AT1A receptor deficiency caused a marked decrease in atherosclerotic lesion size in both the aortic root and arch of male and female mice, without a discernible effect on composition. AT1A receptor deficiency-induced reductions in atherosclerosis were independent of systolic blood pressure and measurements of oxidation and chemoattractants. Aortic AT2 receptor mRNA expression was not altered in AT1A receptor-deficient mice, and AT2 receptor deficiency had no effect on lesion area or cellular composition. Hypercholesterolemia greatly augmented the systemic renin-angiotensin system, as demonstrated by large increases in plasma concentrations of angiotensinogen and angiotensin peptides (Ang II, III, IV, and 4-8). These increases were ablated in hypercholesterolemic AT1A receptor-deficient mice. CONCLUSIONS: AT1A receptor deficiency had a striking effect in reducing hypercholesterolemia-induced atherosclerosis in LDL receptor-negative mice. Hypercholesterolemia was associated with increased systemic angiotensinogen and angiotensin peptides, which were reduced in AT1A receptor-deficient mice. These results demonstrate that hypercholesterolemia-induced stimulation of angiotensin peptide production provides a basis for the marked effect of AT1A receptor deficiency in reducing atherosclerosis.

Amino Acid Sequence↗
PubMed2004

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

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.

Adipose Tissue↗
PubMed2004

Orchidectomy, but not ovariectomy, regulates angiotensin II-induced vascular diseases in apolipoprotein E-deficient mice.

In humans, the incidence and severity of abdominal aortic aneurysms (AAA) are greater in males than in females. Chronic infusion of angiotensin II (AngII) into apolipoprotein E-deficient (apoE(-/-)) mice promotes atherosclerosis and causes the formation of AAAs. Just as human males are more susceptible to developing AAAs, male mice are more susceptible to AngII-induced AAAs. We hypothesized that sex steroid hormones mediate gender differences in AngII-induced AAA through regulation of the renin-angiotensin system. To define the role of ovarian hormones, female apoE(-/-) mice were subjected to ovariectomy or sham operation and infused with AngII (1000 ng/kg x min) for 28 d. Ovariectomy had no effect on AngII-induced atherosclerosis, nor did it influence the incidence or severity of AAA. To define the role of testicular hormones, male apoE(-/-) mice were subjected to orchidectomy (orx) or sham operation and infused with AngII (1000 ng/kg x min) for 28 d. Orx resulted in a profound reduction in AAA incidence (85% vs. 18%, sham vs. orx; P = 0.003) to the level observed in females (25%). However, orx had no effect on AngII-induced reductions in plasma renin concentration or spleen AngII receptor density. In contrast, orx resulted in an increase in atherosclerosis (0.46 +/- 0.07 vs. 1.20 +/- 0.21 mm(2), sham vs. orx; P = 0.002). These results suggest that estrogen does not mediate gender differences in AngII-induced AAA. In contrast, androgens mediate a higher incidence of AngII- induced AAA, through mechanisms that do not appear to involve circulating renin or angiotensin receptor density.

Angiotensin II↗
PubMed2004

Role of metabolism and receptor responsiveness in the attenuated responses to Angiotensin II in mice compared to rats.

Chronic infusion of Angiotensin II (AngII) to rats is a well-characterized model for determining AngII physiology. Genetic manipulations have strengthened knowledge of AngII; however, they do not permit an increase in AngII to be initiated at a selected age, duration and dose. Therefore, exogenous AngII administration remains an important technique to define its biological effect. We previously noted that infusion of AngII to mice had minimal effects compared to the same dose given to rats. In this study, we compared the effects of chronic infusion of the same dose of AngII to C57BL/6 mice and Sprague-Dawley rats, two commonly used rodent models. Rats administered AngII exhibited reductions (by 22%) in body weight, which were not evident in mice. AngII increased blood pressure by 54 mm Hg in rats, but had no effect in mice. Vascular histology demonstrated that AngII caused medial hypertrophy in rats, with adventitial expansion in mice. Plasma concentrations of AngII and its catabolic fragments were elevated (twofold) in mice compared to rats. Angiotensin receptor affinity, density and distribution were similar in rats and mice. Infusion of AngII decreased AngII receptor density in the kidney (by 78%) and spleen (by 29%) of mice, but had no effect in rats. AngII produced a sustained contractile response in rat aortic strips, but minimal responses in mouse aorta. These results demonstrate that differences in circulating angiotensin peptides, AngII receptor regulation, and vascular reactivity contribute to diminished responses to AngII infusion in mice compared to rats. Results from this study suggest that considerably higher doses of AngII may be required to elicit physiologic effects of AngII in mice.

Angiotensin II↗
PubMed2004

Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload.

Activation of the sympathetic nervous system is well documented in heart failure. Our previous studies demonstrated an increase in evoked norepinephrine (NE) release from left ventricle (LV) slices at 10 days of pressure overload. The purpose of this study was to test the hypothesis that presynaptic modulation of NE release contributes to sympathetic activation after pressure overload. We examined the functional status of the presynaptic alpha(2)- and beta(2)-receptors and ANG II subtype 1 (AT(1)) receptors in LV slices from 10-day aortic constricted (AC) and sham-operated (SO) rats. Evoked (3)H overflow from LV slices preloaded with [(3)H]NE was increased in AC rats. The alpha(2)-agonist UK-14,304 decreased evoked (3)H overflow with no differences between groups. The beta(2)-agonist salbutamol increased evoked (3)H overflow with greater sensitivity in slices from AC rats. The beta-antagonist propranolol decreased evoked (3)H overflow from LV slices of AC rats but not controls. ANG II increased evoked (3)H overflow with greater sensitivity in slices from AC rats. These data support the hypothesis that aberrant presynaptic modulation of catecholamine release contributes to sympathetic activation after pressure overload.

Adrenergic Fibers↗
PubMed2004

Mouse models of abdominal aortic aneurysms.

Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.

Angiotensin II↗
PubMed2003

Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes.

Adipocytes secrete a variety of factors, including angiotensinogen, the only known precursor to Angiotensin II (AngII). Recent studies suggest that adipocyte-derived angiotensinogen can contribute to circulating angiotensinogen concentrations and modulate blood pressure; however, an autocrine role for adipocyte-derived angiotensinogen and/or AngII has not been well defined. We sought to determine whether locally produced AngII influences the release of leptin from adipocytes and thus circulating leptin concentrations. In adipocytes from rats treated for 3 d with captopril demonstrating reductions in AngII release, leptin release and plasma leptin concentration were decreased. Incubation of adipocytes with AngII resulted in an increase in leptin mRNA expression and leptin release. To determine the effect of elevated systemic AngII on leptin, rats were infused with AngII (175 ng/kg.min) or saline for 1, 2, or 7 d. Plasma leptin concentration progressively declined with duration of AngII exposure. Basal and AngII-stimulated release of leptin from isolated adipocytes was initially (d 1) increased in AngII-infused rats; thereafter leptin release declined to levels less than control. To define mechanisms for declines in leptin in AngII-infused rats, we examined the effect of alpha-methyl-p-tyrosine on catecholamine turnover and plasma leptin concentration in saline- and AngII (175 ng/kg.min)-infused rats. Infusion of AngII increased catecholamine turnover in adipose tissue. Moreover, sympathetic blockade eliminated differences in plasma leptin concentration between saline- and AngII-infused rats. These results indicate that locally produced AngII directly increases leptin release from adipocytes; however, with elevations in systemic AngII, sympathetic activation counterbalances effects from locally produced AngII.

Adipocytes↗
PubMed2003

Near-infrared spectrometry of abdominal aortic aneurysm in the ApoE-/- mouse.

Abdominal aortic aneurysms (AAAs) occur in 5-7% of people over age 60 in the United States. Early intervention in the disease process could have a significant impact on the incidence of complications and on patient survival, but identifying incipient aneurysms can be difficult. ApoE knockout mice develop AAAs following infusion of angiotensin II (AngII) by osmotic minipump into the subcutaneous space of mice at doses ranging from 500 to 1000 ng kg(-1) min(-1) for 7-28 days. These mice are used as models of AAA development. This study tested the hypothesis that near-IR spectrometry and PCR can determine AngII dose (SEE = 26 ng kg(-1) min(-1), SEP = 37 ng kg(-1) min(-1), r2 = 0.99) and collagen/elastin (C/E) ratio (SEE = 0.38, SEP = 0.39, r2 = 0.85) in mouse aortas.

Angiotensin II↗
PubMed2003

Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice.

OBJECTIVE: We sought to define the temporal characteristics of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and to provide mechanistic insight into the development of this vascular pathology in apolipoprotein E-deficient (apoE-/-) mice. METHODS AND RESULTS: Male apoE-/- mice were infused with AngII for 1 to 56 days. Suprarenal arteries were sequentially sectioned, and cellular features were defined by histologic and immunocytochemical techniques. The initial identified event was medial accumulation of macrophages in regions of elastin degradation. Subsequent medial dissection was associated with luminal dilation and thrombus formation. Thrombi were usually constrained by adventitial tissue, although approximately 10% of mice died due to rupture. Thrombi led to profound inflammation that was characterized by infiltration of macrophages and T and B lymphocytes. Remodeling of the tissues was associated with regeneration of elastin fibers and reendothelialization of the dilated luminal surface. Aneurysmal tissue underwent profound neovascularization. Atherosclerotic lesions were only detected after development of the aneurysms. CONCLUSIONS: The initial event in AngII-induced AAA is a focal dissection in the suprarenal region. The progression of AAA precedes the development of overt atherosclerotic lesions.

Aneurysm↗