In vivo DNA synthesis is not uniformly increased in arterial smooth muscle of young spontaneously hypertensive rats

Mey, Jörg; Daemen, M. J. A. P.; Boonen, Harrie C. M.; Bosman, Fred T.; Dijkstra, Eva; Fazzi, G. E.; Janssen, G.; Schiffers, P. M. H.; Struyker-Boudier, H.A.J.; Vrijdag, M. J. J. F.

doi:10.1097/00004872-199108000-00002

Cited by 11 publications

(3 citation statements)

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“…The aortic DNA content is increased in obese SHR. DNA synthesis is elevated in smooth muscle of large arteries in SHR (26), resulting in medial hypertrophy (27). The increased aortic DNA content may reflect increased cellularity or polyploidy in medial smooth muscle cells.…”

Section: Resultsmentioning

confidence: 99%

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: Resultsmentioning

confidence: 99%

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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“…This is consistent with previous findings, where a significant level of DNA synthesis was observed in 6-week-old rats, although there was no increase in DNA content by 20 weeks of age. 36 Taken together, this suggests that there is a basal but slow rate of cellular turnover in intact, structurally stable, small muscular arteries, a turnover that is increased under conditions of altered flow.…”

Section: Discussionmentioning

confidence: 96%

Smooth Muscle Cell Changes During Flow-Related Remodeling of Rat Mesenteric Resistance Arteries

Buus

Pourageaud

Fazzi

et al. 2001

Circulation Research

124

128

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Abstract-To obtain information on the molecular and cellular mechanisms of flow-induced arterial remodeling, we analyzed the morphology and smooth muscle cell (SMC) characteristics in rat mesenteric resistance arteries after interventions that decreased and increased flow. Juvenile male Wistar Kyoto rats were subjected to surgery that, compared with control arteries, provided arteries with chronic low flow and chronic high flow. Low flow resulted in a decreased passive lumen diameter, hypotrophy of the artery wall, and both loss and decreased size of SMCs. Time course studies, with intervention length ranging from 2 to 32 days of altered blood flow, showed that the narrowing of the lumen diameter in low-flow arteries appeared within 2 days and that an early dedifferentiation of SMC phenotype was indicated by markedly reduced levels of desmin mRNA. High flow resulted in an increased passive lumen diameter and in hypertrophy of the artery wall. The hypertrophy resulted from SMC proliferation because SMC number, measured by the 3D-dissector technique, was increased and immunohistochemical assessment of proliferating cell nuclear antigen also showed an increase. The widening of high-flow arteries required 16 days to become established, at which time desmin mRNA was reduced. This time was also required to establish changed wall mass in both low-flow and high-flow arteries. Apoptotic cells detected by TdT-mediated dUTP-biotin nick end labeling staining were mainly located in the medial layer, and evaluation of DNA fragmentation indicated that increased apoptosis occurred in both low flow and high flow. This study shows for the first time direct evidence that reduced and elevated blood flow in resistance arteries produce, respectively, decrease and increase in SMC number, with dedifferentiation of the SMCs in both cases.

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“…Furthermore, application of this method has been extended to research involving the proliferation of vascular cells following exposure of laboratory animals to a variety of chemical and physical stresses (4,5,11,12). In many of these studies, the number of proliferating cells was determined immunohistochemically by counting the BrdU-labeled nuclei in serial (histological) sections of specific vessels.…”

Section: Discussionmentioning

confidence: 99%

Flow cytometric determination of cell proliferation in hypertensive blood vessels

Hirsch¹,

Tozzi

Das³

et al. 1999

Cytometry

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In vivo DNA synthesis is not uniformly increased in arterial smooth muscle of young spontaneously hypertensive rats

Cited by 11 publications

References 0 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.

Smooth Muscle Cell Changes During Flow-Related Remodeling of Rat Mesenteric Resistance Arteries

Flow cytometric determination of cell proliferation in hypertensive blood vessels

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