Effects of hypertension and its reversal on aortic metabolism in the rat.

Brecher, Peter; Chan, C T; Franzblau, Carl; Faris, Barbara; Chobanian, Aram V.

doi:10.1161/01.res.43.4.561

Cited by 61 publications

(21 citation statements)

References 35 publications

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“…16 Similar findings with regard to the augmented arterial wall collagen and elastin content in aortas of deoxycorticosterone acetatesalt and spontaneously hypertensive rats treated with reserpine, hydralazine, and hydrochlorothiazide have also been reported. 22 In view of the fact that the increased collagen synthesis associated with experimental or genetic forms of hypertension is completely reversed by antihypertensive therapy, 8 these results suggest that the rate of breakdown of the previously synthesized connective tissue is likewise decreased. Since incomplete reversal of the increased collagen and elastin content occurs with therapy, 20 -K it is not surprising that normalization of passive stiffness following nephrectomy was not found in this study.…”

Section: Discussionmentioning

confidence: 99%

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Effects of hypertension and its reversal on canine arterial wall properties.

Cox

Bagshaw

1988

Hypertension

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SUMMARY Segments of carotid, femoral, saphenous, and left circumflex coronary arteries were obtained from control, renal hypertensive, and nephrectomized hypertensive dogs for in vitro study of mechanical properties. Hypertension was produced in two-kidney dogs by unilateral renal artery constriction. After 3 months, the compromised kidney was removed in half of the dogs. Mean arterial pressure was significantly elevated in the hypertensive dogs after 3 months (127 ± 2 vs 94 ± 1 mm Hg for controls) and partially returned toward normal 3 months after nephrectomy (105 ± 2 mm Hg). Pressure-diameter relations were determined under conditions of rmnrimnm active and passive smooth muscle activation. Contiguous segments were used for the determination of water and connective tissue content. Hypertension was associated with increased passive arterial wall stiffness at most sites, with a partial return toward normal after nephrectomy. Maximum responses to smooth muscle activation (active stress and constriction response) were augmented in arteries from hypertensive dogs and partially returned toward normal in the nephrectomized hypertensive group. The elastin content of these arteries was unchanged, while collagen content was nonuniformly decreased in renal hypertensive dogs. Small decreases were found in the radius-wall thickness ratio of some arteries. No significant mechanical changes occurred in the saphenous artery. The largest hypertension-related changes were found in the coronary arteries, which also exhibited the smallest recovery toward normal properties after nephrectomy. 1 -2 These include changes in arterial smooth muscle mechanics, wall composition, responsiveness to vasoactive agents, and functional properties of smooth muscle cell membranes.3 -6 Some of these changes in arterial wall properties are thought to be responsible for the pathogenesis of hypertension, 3 -6 while some have been shown to be the direct result of the elevated blood pressure per se.7 -9 Elevated blood pressure is presumed to exert some influence on the synthetic machinery in vascular smooth muscle cells, causing them to alter the balance between synthesis and degradation of wall components. The exact nature of these signals has not been clearly defined, but they are thought to be due at least in part to increased arterial wall stress or strain. 10 These altered arterial wall properties have profound effects on circulatory function in the hypertensive subject, including changes in peripheral resistance, neural control of the circulation, and the mechanical work of the heart. Elevated arterial pressure also produces increased wear and tear on blood vessels, ultimately leading to pathological changes in the coronary, cerebral, and renal circulations and hence to the increased morbidity and mortality 1 '-14 associated with hypertension.The goal of antihypertensive therapy is to lower or normalize arterial blood pressure, thereby removing at least those components of the signal(s) producing arterial wall degenerative changes in hypertensi...

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Section: Discussionmentioning

confidence: 99%

“…1618 - 20 - 22 Accordingly, this study attempted to determine the reversibility of arterial wall changes associated with renal hypertension in the dog.…”

Section: Smentioning

confidence: 99%

Effects of hypertension and its reversal on canine arterial wall properties.

Cox

Bagshaw

1988

Hypertension

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“…Blood pressure was measured by a standard tail cuff technique (Narco Bio Systems, Inc.) on unanesthetized rats maintained quietly at 35°C for 5-10 minutes in a specially constructed chamber (Brecher et al, 1978). The preparation of the hypertensive and control groups followed methods previously described by Brecher et al (1978).…”

Section: Methodsmentioning

confidence: 99%

“…The hypertensive model of uninephrectomized deoxycorticosterone-salinetreated rats has been shown by others to result in a rise in systolic blood pressure beginning as early as the second week of treatment, from a level of approximately 170 mm Hg to 220 mm Hg from 4 to 8 weeks of treatment (Brecher et al, 1978). Our hypertensive LVH group achieved a similar level of systolic arterial hypertension, averaging 201 mm Hg for weeks 5-7 of treatment, in contrast to a mean normotensive level of 129 mm Hg in the control rats.…”

Section: Limitations Of the Experimental Modelmentioning

confidence: 95%

The influence of pressure overload left ventricular hypertrophy on diastolic properties during hypoxia in isovolumically contracting rat hearts.

Lorell¹,

Wexler²,

Momomura³

et al. 1986

Circulation Research

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SUMMARY. We tested the hypothesis that there is an enhanced susceptibility in hypertrophied cardiac muscle to develop decreased diastolic distensibility of the left ventricle in response to hypoxia. The effects of brief hypoxia (3 minutes) were studied in rats with and without chronic left ventricular pressure overload hypertrophy using an isolated buffer-perfused and isovolumic (balloon-in-left ventricle) heart preparation with excised pericardium and vented right ventricle. We compared hypertrophied hearts from hearts from hypertensive uninephrectomized WistarKyoto rats (» = 12) with normotensive uninephrectomized age-matched controls (n = 13). Coronary flow was held constant and adjusted so that an identical flow per gram left ventricular weight was achieved in both groups. The left ventricular balloon volume was adjusted to produce an initial left ventricular end-diastolic pressure of 10 mm Hg in both groups and was held constant thereafter so that changes in left ventricular end-diastolic pressure during hypoxia represented changes in diastolic chamber distensibility. Under aerobic conditions, left ventricular systolic pressure was 66% higher in the hypertrophied hearts than in the controls, but there was no difference in the rate or extent of left ventricular relaxation as estimated by the exponential time constant of pressure decay and the asymptote to which pressure decayed. In response to hypoxia, left ventricular end-diastolic pressure was significantly higher in the hypertrophied hearts than in the controls (37 ± 5 vs. 22 ± 5 mm Hg, P < 0.001). In response to hypoxia, the rate of left ventricular relaxation was depressed to a comparable degree in both groups, but there was a greater upward shift in the asymptote to which pressure decayed in the hypertrophied hearts. Hypoxia-induced coronary vasodilation as assessed by the change in coronary vascular resistance was similar in the hypertrophied and control hearts (2.9 ± 0.5 vs. CARDIAC hypertrophy is a compensatory response to chronic pressure or volume overload of the heart. However, adaptive cardiac hypertrophy may result in an enhanced vulnerability to ischemia or hypoxia,* as manifested by a decrease in diastolic distensibility. Bache et al. (1984a) have shown that pacing tachycardia in dogs with chronic left ventricular (LV) hypertrophy without coronary stenoses produces myocardial ischemia associated with a substantial increase in left ventricular end-diastolic pressure. A similar dramatic and reversible decrease in left ventricular diastolic distensibility has been * In this paper, hypoxia will be used to indicate an abnormally low level of tissue oxygenation due to hypoxemia, an abnormally low arterial oxygen content. Ischemia will mean an abnormally low level of myocardial perfusion.

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“…Cholesteryl ester radioactivity was measured by the method of Hashimoto and Fogelman. 20 Other biochemical and chemical methods: disrupted hepatocytes and vesicles were assayed for 5'-nucleotidase, 21 acid phosphatase, 22 and protein.…”

Section: Methodsmentioning

confidence: 99%

Accumulation of cholesteryl ester and lipid droplets in macrophages after uptake of cholesterol-rich necrotic products.

Wong¹,

Hashimoto²

1987

Arteriosclerosis

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The prevalence of degenerated cells in the thickened intima of cholesterol-fed animals suggested that necrotic regions might become a focus for lesion development by attracting histiocytes or monocytes. We propose that cholesterol-rich necrotic products scavenged by macrophages incite the accumulation of cholesteryl ester and the formation of cholesteryl ester droplets. The feasibility of this hypothesis was tested with readily available materials, namely, lung macrophages and plasma membrane vesicles (PMV) released from dying cholesterol-rich and normal hepatocytes. PMV from cholesterol-rich hepatocytes contained 30-fold more cholesteryl ester than PMV from normal hepatocytes. Degradation of 125 I-PMV to trichloroacetic acid-soluble products by macrophages was fourfold higher than that of 125 l-acetylated low density lipoprotein (acetyl-LDL) at 100 /xg/ml of ligand in the incubation medium. Within this concentration range, degradation of PMV increased almost linearly with increasing concentrations of PMV, while the degradation of acetyl-LDL followed a saturation curve. Cholesterol-rich PMV increased the cholesteryl ester content of macrophages fourfold and augmented the incorporation of oleate threefold relative to normal PMV. These studies were extended to aortic smooth muscle cells. As with hepatocyte-PMV, smooth muscle cell-PMV was internalized and degraded by macrophages T here is little doubt that abnormally high concentrations of low density lipoprotein (LDL) in plasma incite atherogenesis and that lipoprotein cholesterol accumulates in atherosclerotic lesions as cholesteryl ester droplets in macrophages. 1 The events in the formation of atherosclerotic lesions are understood in outline only. Cell culture studies have indicated that modification of LDL either by chemical reagents 2 " 4 or by conditioning with endothelial cells 5 is necessary to stimulate the accumulation of cholesteryl ester in macrophages, implicating abnormal instead of native LDL in atherogenesis. Indeed, modified LDL isolated from lesions abet in vitro accumulation of macrophage cholesteryl ester.6 Low density lipoprotein modified by incubation with endothelial cells also exhibit cytotoxic properties.7 The latter may also play a role in atherogenesis.We have considered an alternative pathway for the formation of cholesteryl ester-rich macrophages which may or may not involve modified LDL. Prevalence of necrotic cells in thickened intima of hypercholesterolemic swine 8 ' 9 suggested that necrotic products may become another source of cholesterol for infiltrated macrophages over and above that provided by modified LDL. A common response of several cell types to injury and the dying process is the formation of blebs on the cell surface which subsequently pinch off to form plasma membrane vesicles. 10 " 12 These vesicles are enriched with cholesterol and could conceivably be enriched even more if derived from a parent cholesterol-rich cell. We propose that plasma membrane vesicles (PMV) released from dying cells in the thickened inti...

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Effects of hypertension and its reversal on aortic metabolism in the rat.

Cited by 61 publications

References 35 publications

Effects of hypertension and its reversal on canine arterial wall properties.

Effects of hypertension and its reversal on canine arterial wall properties.

The influence of pressure overload left ventricular hypertrophy on diastolic properties during hypoxia in isovolumically contracting rat hearts.

Accumulation of cholesteryl ester and lipid droplets in macrophages after uptake of cholesterol-rich necrotic products.

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