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Biomedical subjects

A Chobanian

Publications and source records attributed to A Chobanian.

9 recordsLinked to original sources
PubMed1992

Age-related changes in fibronectin expression in spontaneously hypertensive, Wistar-Kyoto, and Wistar rat hearts.

The effects of age and blood pressure on fibronectin expression in the rat heart were studied in the normotensive Wistar and Wistar-Kyoto (WKY) strains and in the spontaneously hypertensive rat (SHR). Fibronectin mRNA expression decreased threefold between 10 and 40 weeks of age in Wistar hearts, with changes of similar magnitude occurring between 6 and 24 weeks in WKY rats. In contrast, no decrease in fibronectin mRNA was observed in SHR hearts during this time span. These results are in contrast to changes observed previously in the aorta, where an increase in fibronectin mRNA occurred with age in all three rat strains. Ribonuclease protection analysis showed a small age-specific increase in the relative content of EIIIA+ fibronectin mRNA isoforms in hearts from Wistar rats, whereas no change was found in the relative amount of either EIIIA or EIIIB isoforms in SHR hearts. Changes similar to those observed for fibronectin mRNA, although of different magnitudes, were observed in mRNA levels for collagen alpha 1(III) and beta 1 integrin. In Wistar hearts, collagen alpha 1(III) mRNA levels decreased fivefold to sixfold between 10 and 40 weeks of age, whereas a twofold to threefold decrease in beta 1 integrin was observed in WKY hearts between 6 and 24 weeks of age. Western blot analysis revealed a positive correlation between fibronectin mRNA and protein for age-dependent changes in ventricular tissue but not in the atria, suggesting that the regulation of fibronectin expression during the changes common to both aging and hypertrophy could involve both transcriptional and posttranscriptional mechanisms.

Age Factors↗
PubMed1991

High-normal blood pressure progression to hypertension in the Framingham Heart Study.

This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category. Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure. The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for women (95% CI, 1.5-2.3; p less than 0.0001). The age-adjusted relative risks estimated by the proportional hazards model were 3.36 for men and 3.37 for women (p less than 0.001). Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal. For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension. These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Regulation of intracellular calcium by cell pH in vascular smooth muscle cells.

Intracellular calcium (Cai2+) and intracellular pH (pHi) are important regulators of a variety of intracellular processes. Cai2+ is a regulator of muscle contraction, but the role of pHi is unclear. The purpose of this study was to determine the effect of alterations of pHi on Cai2+. A7r5 vascular smooth muscle cells (VSMC) were grown to confluence on glass cover slips. Cai2+ was determined with the fluorescent probe fura-2 and pHi with 2,7-bis-carboxyethyl-5(6)-carboxy-fluorescein (BCECF). Alkalinization of the VSMC by exposure to 20 mM NH4Cl (delta pHi 0.41 +/- 0.07) resulted in a rise in Cai2+ from 99 +/- 8 to 146 +/- 13 nM (n = 5) in the presence of extracellular Ca2+ (Cao2+). In the absence of Cao2+, NH4Cl-induced alkalinization also resulted in a Cai2+ rise (delta Cai2+ = 26 +/- 4 nM, n = 5). Similar changes in Cai2+ were observed when cells were alkalinized by exposure to nigericin in a KCl buffer (pH 7.7). Neither 100 microM verapamil or 100 microM 8,8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate HCl (TMB-8) altered the alkaline-induced changes. After cellular Ca2+ stores were partially depleted by exposure to AVP in a Ca2+-free solution, subsequent cell alkalinization induced no changes in Cai2+. These results demonstrate that alkalinization of VSMCs leads to a rise in cytosolic Ca2+ via release of intracellular Ca2+ stores. The intracellular Ca2+ storage sites appear to be the same as those sites sensitive to AVP. Thus pHi may regulate Cai2+ and thereby play a role in the regulation of vascular smooth muscle tone.

Ammonium Chloride↗
PubMed1988

Overview: hypertension and atherosclerosis.

Many large-scale trials of drug treatment for hypertension have shown an apparent lack of benefit with regard to the incidence of complications related to atherosclerosis. Recent experimental evidence has contributed to an understanding of the pathogenesis of hypertensive vascular disease, although exact mechanisms by which hypertension and antihypertensive drugs influence the atherosclerotic process are still poorly defined. In animal models, hypertension appears to induce a sequence of changes in endothelial cells, smooth muscle cells, and endothelial permeability. However, increased lipid deposition in the intima and acceleration of atherosclerosis appear to require elevation of plasma lipid levels. Some beta-blockers have been found to retard the development of atherosclerosis in the cholesterol-fed rabbit model. The clinical applicability of these interesting research findings awaits further investigation.

Animals↗
PubMed1988

Apolipoprotein gene expression in the rabbit: abundance, size, and distribution of apolipoprotein mRNA species in different tissues.

We have used human apolipoprotein cDNAs as hybridization probes to study the relative abundance and distribution of apolipoprotein mRNAs in rabbit tissues by RNA blotting analysis. The tissues surveyed included liver, intestine, lung, pancreas, spleen, stomach, skeletal muscle, testis, heart, kidney, adrenal, aorta, and brain. We found that liver is the sole or major site of synthesis of apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, and apoE, and the intestine is a major site of synthesis of apoA-I, apoA-IV, and apoB. Minor sites of apolipoprotein mRNA synthesis were as follows: apoA-I, liver and skeletal muscle; apoA-IV, spleen and lung; apoB, kidney; apoC-II and apoC-III, intestine. ApoE mRNA was detected in all tissues surveyed with the exception of skeletal muscle. Sites with moderate apoE mRNA (10% of the liver value) were lung, brain, spleen, stomach, and testis. All rabbit mRNAs had forms with sizes comparable to their human counterparts. In addition, hybridization of hepatic and intestinal RNA with human apoA-IV and apoB probes produced a second hybridization band of approximately 2.4 and 8 kb, respectively. Similarly, hybridization of rabbit intestinal RNA with human apoC-II produced a hybridization band of 1.8 kb. The 8 kb apoB mRNA form may correspond to the apoB-48 mRNA, whereas the apoA-IV- and apoC-II-related mRNA species have not been described previously. This study provides a comprehensive survey of the sites of apolipoprotein gene expression and shows numerous differences in both the abundance and the tissue distribution of several apolipoprotein mRNAs between rabbit and human tissues. These findings and the observation of potentially new apolipoprotein mRNA species are important for our understanding of the cis and trans acting factors that confer tissue specificity as well as factors that regulate the expression of apolipoprotein genes in different mammalian species.

Animals↗
PubMed1987

Vascular changes in hypertension.

Hypertension can directly damage blood vessels, and leads to renal failure, intracranial bleeds, and lacunar infarctions. Of equal importance is the effect of hypertension on the development of atherosclerosis. Specific changes in both the microvasculature and macrovasculature vary depending on the degree and rapidity of blood pressure elevation. Changes in the intima and media can lead to significant narrowing of vessels and ischemia in various tissues. In addition, changes in small-resistance vessels contribute to changes in peripheral-vasculature resistance and thus affect blood pressure regulation. Treatment of moderate to severe elevation in blood pressure clearly results in a decrease in the incidence of stroke. However, evidence that treating mild hypertension reduces coronary events is less convincing. Antihypertensive therapy may result in partial regression of vascular changes, especially fibrinoid necrosis seen in malignant hypertension, but more work needs to be done to clearly define the roles of specific drugs in preventing or regressing hypertensive vascular disease.

Animals↗
PubMed1987

Effects of calcium channel antagonists and other antihypertensive drugs on atherogenesis.

This paper reviews published data concerning the effects of antihypertensive drugs on the development of atherosclerosis in experimental animal models with hyperlipoproteinaemia. Emphasis is placed on the influence of calcium channel antagonists on this process, and the potential mechanisms responsible for the effect. In addition, studies of the action of beta-receptor antagonists on atherogenesis are also summarized. The results indicate that several antihypertensive drugs may inhibit or retard experimentally-induced atherogenesis, even in normotensive animals, although the mechanisms for the effects remain poorly understood.

Adrenergic beta-Antagonists↗
PubMed1968

Metabolism of sex hormones in the aortic wall.

The metabolism of labeled sex hormones was examined in human, canine, and rat aortas. Isolated arterial tissue converted estrone to estradiol, estradiol to estrone, and estrone sulfate to estrone and estradiol. The arterial wall also appeared to metabolize testosterone to androstenedione and an unidentified, relatively nonpolar derivative. Both estrogens and testosterone appeared to enter the arterial wall rapidly. No competition in arterial uptake between the two hormones was apparent. No specific arterial binding of estradiol could be demonstrated. The concentration of estradiol-(3)H in the canine aorta exceeded that in the plasma 1-6 hr after estradiol-(3)H administration. The uptake and disappearance of estradiol-(3)H in the aorta generally resembled the patterns observed in body tissues other than the adrenal gland and uterus. The uptake of estradiol-(3)H was greatest in the adrenal gland while its retention was maximum in the uterus.

17-Ketosteroids↗