1989 Corcoran lecture: adaptive and maladaptive responses of the arterial wall to hypertension.

Chobanian, Aram V.

doi:10.1161/01.hyp.15.6.666

Cited by 134 publications

(55 citation statements)

References 50 publications

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“…It was reported that intimal thickening of large vessels develops with aging in male SHR due to increased deposition of extracellular matrix and increased migration of mononuclear cells (25). This is compatible with the histological changes of the carotid artery seen in our female obese SHR.…”

Section: Resultssupporting

confidence: 91%

Obesity Induced by Neonatal Monosodium Glutamate Treatment in Spontaneously Hypertensive Rats: An Animal Model of Multiple Risk Factors.

et al. 1998

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The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases. (Hypertens Res 1998; 21: 1-6) Key Words: insulin resistance, diabetes mellitus, syndrome X, atherosclerosis, animal model Obesity, hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and hyperlipidemia frequently exist in the same individual, and clustering of these closely related risk factors markedly increases the incidence and prevalence of atherosclerotic diseases (1-7). Insulin resistance and consequent hyperinsulinemia or visceral fat accumulation may play a pathogenetic role in the clustering of risk factors, i. e. , metabolic syndrome X. However, the relationship among these risk factors, especially that between hypertension and other metabolic diseases, is controversial (5-8). Our understanding of metabolic syndrome X may be enhanced by the development of an animal model of this syndrome. We therefore designed the present study to induce experimental obesity in spontaneously hypertensive rats (SHR) by treatment with small or large doses of monosodium glutamate (MSG). MSG induces hypothalamic damage when given during neonatally, leading to stunted growth and obesity (9). We studied the effects of MSG-induced obesity on hypertension, glycemia, lipidemia, and the development of macrovascular changes in the obese SHR. Materials and MethodsSHR were from our inbred colony and were bred in specific-pathogen-free conditions at Kyushu University Animal Center, where both temperature and lighting (on from 8:00 am to 8:00 pm) were controlled. They had free access to tap water and a standard chow diet, which contained 51.6% carbohydrate, 24.8% protein, 7.0% minerals, 4.4% fat, and 3.5% cellulose (flea Japan Inc., Tokyo, Japan). Animals were cared for as directed by guidelines of Kyushu University. Female newborn SHR were treated intrap...

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Section: Resultssupporting

confidence: 91%

Obesity Induced by Neonatal Monosodium Glutamate Treatment in Spontaneously Hypertensive Rats: An Animal Model of Multiple Risk Factors.

et al. 1998

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“…However, the very large difference found suggests that increased transcription is the main factor in the greater concentration of mRNA found, although differences in stability may also contribute in part. The present study demonstrates greater abundance of transcripts for prepro-ET-1, but in our previous study 11 and other investigations of the vascular changes in DOCA-salt hypertension as well as in other models of hypertension, 17 it has been clearly demonstrated that a hypertrophic response occurs in the blood vessel wall. This hypertrophy affects to a certain degree the endothelium 17 as well as smooth muscle cells and other components of the blood vessel wall.…”

Section: Discussioncontrasting

confidence: 48%

Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats.

1993

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We have recently shown that the content of iramunoreactive endothelin-1 is increased in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats compared with uninephrectomized control rats. We have also found by immnnohistochemistry a significant increase in immunoreactive endothelin-1 in endothelial cells of aorta and mesenteric arteries of DOCA-salt hypertensive rats. In the present study, we investigated preproendothelin-1 gene expression in blood vessels of DOCA-salt hypertensive rats and uninephrectomized control rats. Northern blot analysis using a specific "P-labeled complementary RNA probe for rat preproendothelin-1 of 319 base pairs revealed a fourfold to fivefold increase in abundance of preproendothelin-1 messenger RNA transcripts In both aorta and mesenteric arteries from DOCA-salt hypertensive rats. Thus, increased immunoreactive endothelin-1 content in blood vessels of DOCA-salt hypertensive rats is secondary to increased preproendothelin-1 gene expression. Exaggerated expression of the preproendothelin-1 gene in mineralocorticoid hypertension may contribute to the maintenance of elevated blood pressure.

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“…Changes to the geometric configuration of vessels may lead to smooth muscle cell hypertrophy and increased collagen. The intimal layer of these stiffened vessels then becomes vulnerable to atherosis and to increased lipoprotein, albumin, and leukocyte permeability (28,29). Thus, an early effect of SLE on vascular stiffening may set the stage for an acceleration of the atherosclerotic process through traditional risk factors.…”

Section: Discussionmentioning

confidence: 99%

Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus

Selzer¹,

Sutton-Tyrrell²,

Fitzgerald³

et al. 2004

Arthritis & Rheumatism

193

134

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Objective. To examine and compare risk factors for various stages of subclinical vascular disease in different vascular beds (carotid and aorta) in women with systemic lupus erythematosus (SLE) who have not yet developed clinical cardiovascular disease.Methods. This cross-sectional study was conducted in 214 women without clinical cardiovascular disease who were enrolled in the Pittsburgh Lupus Registry. B-mode ultrasound was used to measure carotid plaque and intima-media wall thickness (IMT). Doppler probes were used to collect pulse-wave velocity waveforms from the right carotid and femoral arteries as a measure of aortic stiffness. All risk factor data were collected on the day of the ultrasound examinations.Results. The mean ؎ SD age of the women was 45.2 ؎ 10.5 years and the median SLE disease duration was ϳ9 years. Sixty-eight (32%) of the women had at least 1 focal plaque. The mean ؎ SD IMT was 0.71 ؎ 0.1 mm, and the mean ؎ SD pulse-wave velocity was 5.96 ؎ 1.6 meters/second. Using logistic regression, we found that determinants of plaque included older age, higher systolic blood pressure, lower levels of high-density lipoprotein 3, and antidepressant use. Determinants of plaque severity were older age, higher systolic blood pressure, lower levels of albumin, and smoking. Independent determinants of the highest quartile of IMT were older age, higher pulse pressure, lower levels of albumin, elevated C-reactive protein levels, high cholesterol, and higher levels of glucose. Higher aortic stiffness was associated with older age, higher systolic blood pressure, higher C3 levels, lower white blood cell count, higher insulin levels, and renal disease.Conclusion. In women with SLE, the risk factors associated with carotid plaque and IMT are those typically associated with cardiovascular disease in the general population, whereas the risk factors associated with vascular stiffness include SLE-specific variables related to immune dysregulation and complement metabolism. The high prevalence of cardiovascular disease among lupus patients may result from both early adverse effects on vascular stiffening as well as later promotion of wall thickening and plaque through inflammatory-mediated processes. These observations provide clues for future mechanistic studies.Systemic lupus erythematosus (SLE) affects primarily women and causes chronic vascular inflammation. Women with SLE, particularly those under age 45 years, experience higher than expected rates of clinical cardiovascular disease, i.e., hypertension (1-3), myocardial infarction (1,4), and stroke (4). In addition to traditional cardiovascular risk factors, other factors specifically associated with SLE appear to be equally, if not more, important (5,6). It is likely that these factors are related to the underlying immune-mediated, inflammatory processes inherent in SLE.Although the pathogenesis of vascular disease in SLE is unknown, it is thought to be multifactorial and of atherosclerotic origin. Atherosclerosis involves both atherosis (fatty degeneration) an...

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1989 Corcoran lecture: adaptive and maladaptive responses of the arterial wall to hypertension.

Cited by 134 publications

References 50 publications

Obesity Induced by Neonatal Monosodium Glutamate Treatment in Spontaneously Hypertensive Rats: An Animal Model of Multiple Risk Factors.

Obesity Induced by Neonatal Monosodium Glutamate Treatment in Spontaneously Hypertensive Rats: An Animal Model of Multiple Risk Factors.

Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats.

Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus

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