scholarly journals BLOOD PRESSURE, CHOLESTEROL CONTENT OF SERUM AND TISSUES, AND ATHEROGENESIS IN THE RAT

1958 ◽  
Vol 107 (4) ◽  
pp. 581-598 ◽  
Author(s):  
Q. B. Deming ◽  
E. H. Mosbach ◽  
M. Bevans ◽  
M. M. Daly ◽  
L. L. Abell ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cholesterol Content ◽  
Local Effect ◽  
High Serum ◽  
Atherosclerotic Lesions ◽  
Human Atherosclerosis ◽  
Desoxycorticosterone Acetate ◽  
Tissue Cholesterol ◽  
Atherosclerotic Changes ◽  
Renal Artery Constriction

Rats on a stock diet with added cholesterol, cholic acid, and thiouracil developed increased concentrations of cholesterol, total lipide, and beta lipoprotein in the serum, and an increased content of cholesterol in the liver and carcass, despite the fact that the diet produced a cessation of endogenous cholesterol synthesis. Rats with high serum lipide concentrations developed intimal lesions similar to those of human atherosclerosis. The induction of hypertension by desoxycorticosterone and salt accelerated the development of hypercholesterolemia, hyperlipemia, increase in tissue cholesterol content, and atherosclerotic changes in the intima. Hypertension induced by renal artery constriction also intensified the hypercholesterolemia and hyperlipemia. On the other hand, rats receiving desoxycorticosterone acetate without salt or salt without desoxycorticosterone acetate did not show any intensification of hypercholesterolemia or hyperlipemia. The extent of the atherosclerotic lesions was correlated with the concentration of cholesterol in the serum. There was also a positive correlation between blood pressure and the degree of hypercholesterolemia. It remained uncertain whether the increase in atherosclerosis in the hypertensive animals was dependent on the increased lipide content of serum and tissues or on a local effect of the elevated blood pressure.

Wnt5a Promotes Lysosomal Cholesterol Egress and Protects Against Atherosclerosis

2021 ◽  
Author(s):  
Sara Awan ◽  
Magalie Lambert ◽  
Ali Imtiaz ◽  
Fabien Alpy ◽  
Catherine Tomasetto ◽  
...  
Keyword(s):  
Dietary Cholesterol ◽  
Cell Types ◽  
Cholesterol Content ◽  
Cholesterol Homeostasis ◽  
Cholesterol Trafficking ◽  
Atherosclerotic Lesions ◽  
Crucial Component ◽  
Multiple Cell ◽  
Niemann Pick

Background: Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and two lysosomal proteins, the Niemann-Pick C1 (NPC1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear. As the Wnt ligand, Wnt5a inhibits the intracellular accumulation of cholesterol in multiple cell types, we tested whether Wnt5a interacts with the lysosomal cholesterol export machinery and studied its role in atherosclerotic lesions formation. Methods: We generated mice deleted for the Wnt5a gene in vascular smooth muscle cells (VSMCs). To establish whether Wnt5a also protects against cholesterol accumulation in human VSMCs, we used a CRISPR/Cas9 guided nuclease approach to generate human VSMCs knockout for Wnt5a. Results: We show that Wnt5a is a crucial component of the lysosomal cholesterol export machinery. By increasing lysosomal acid lipase expression, decreasing metabolic signaling by the mTORC1 kinase, and through binding to NPC1 and NPC2, Wnt5a senses changes in dietary cholesterol supply and promotes lysosomal cholesterol egress to the endoplasmic reticulum (ER). Consequently, loss of Wnt5a decoupled mTORC1 from variations in lysosomal sterol levels, disrupted lysosomal function, decreased cholesterol content in the ER, and promoted atherosclerosis. Conclusions: These results reveal an unexpected function of the Wnt5a pathway as essential for maintaining cholesterol homeostasis in vivo.

Effects of aldosterone on blood pressure and glucose-6-phosphate dehydrogenase activity of heart muscle

1969 ◽  
Vol 47 (2) ◽  
pp. 193-197 ◽  
Author(s):  
C. C. Liew ◽  
A. G. Gornall
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Heart Muscle ◽  
Specific Activity ◽  
Systolic Pressure ◽  
Experimental Hypertension ◽  
Low Doses ◽  
Significant Elevation ◽  
Desoxycorticosterone Acetate ◽  
Glucose 6 Phosphate Dehydrogenase

A study was made of the effects of aldosterone on the activity of heart muscle glucose-6-phosphate dehydrogenase (G6PDH) in relation to the pathogenesis of experimental hypertension. In a 17-day experiment, with rats given daily 1-μg doses of aldosterone/100 g body weight, no change in systolic pressure occurred and the specific activity (s.a.) of heart muscle G6PDH declined. Rats receiving daily 100 μg of aldosterone, or 500 μg of desoxycorticosterone acetate (DOCA) per 100 g body weight, showed a significant elevation of systolic pressure by the 17th day. This effect was accompanied by increases in the s.a. of heart muscle G6PDH, apparently preceding the development of hypertension. Evidence for a homeostatic role for aldosterone was revealed by the ability of low doses to prevent a decline in s.a. of cardiac G6PDH during fasting, and to reverse the increase produced by DOCA.

scholarly journals OBSERVATIONS ON THE RÔLE OF THE RAT KIDNEY IN HYPERTENSION CAUSED BY DESOXYCORTICOSTERONE ACETATE

1949 ◽  
Vol 89 (6) ◽  
pp. 631-641 ◽  
Author(s):  
Sydney M. Friedman ◽  
Constance L. Friedman
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Renal Mass ◽  
Rat Kidney ◽  
Drinking Water Treatment ◽  
Albino Rats ◽  
Cent Saline ◽  
Renal Changes ◽  
Desoxycorticosterone Acetate ◽  
Pellet Form

Desoxycorticosterone acetate in pellet form was administered for 51 days to albino rats of the Sherman strain which also received 1 per cent saline as drinking water. Treatment was stopped in representative groups at 25, 37, and 51 days so that the regression of blood pressure and renal changes could be observed. It was noted that both the elevation in blood pressure during treatment and its reversal when treatment was stopped were closely correlated with corresponding changes in renal mass. In the time for which the process was studied it did not become irreversible. Removal of both kidneys from DCA-treated animals aggravated the hypertension, suggesting that the kidneys are actively concerned with the excretion and possible inactivation of the steroid.

Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats

1976 ◽  
Vol 54 (3) ◽  
pp. 314-321
Author(s):  
A. C. Darke ◽  
P. G. Nair ◽  
P. Gaskell
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Vascular Reactivity ◽  
Experimental Hypertension ◽  
Hypertensive Rats ◽  
Opening Pressure ◽  
Critical Opening ◽  
Resistance Vessels ◽  
Before And After ◽  
Desoxycorticosterone Acetate

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA–NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA–NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA–NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.

DESOXYCORTICOSTERONE ACETATE: STUDIES ON THE REVERSIBILITY OF ITS EFFECT ON BLOOD PRESSURE AND RENAL DAMAGE IN RATS1

Endocrinology ◽  
1949 ◽  
Vol 45 (4) ◽  
pp. 435-445 ◽  
Author(s):  
A. I. KNOWLTON ◽  
E. N. LOEB ◽  
B. C. SEEGAL ◽  
H. C. STOERK
Keyword(s):  
Blood Pressure ◽  
Renal Damage ◽  
Desoxycorticosterone Acetate

scholarly journals Effects of Desoxycorticosterone Acetate on Cholesterolemia, Blood Pressure and Atherogenesis in Chicks

Circulation ◽  
1951 ◽  
Vol 4 (2) ◽  
pp. 262-269 ◽  
Author(s):  
J. STAMLER ◽  
R. PICK ◽  
L. N. KATZ ◽  
E. Levinson ◽  
P. Johnson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Desoxycorticosterone Acetate

scholarly journals THE EFFECT OF DESOXYCORTICOSTERONE ACETATE ON BLOOD PRESSURE, RENAL FUNCTION, AND ELECTROLYTE PATTERN IN THE INTACT RAT

1948 ◽  
Vol 87 (4) ◽  
pp. 329-338 ◽  
Author(s):  
Sydney M. Friedman ◽  
John R. Polley ◽  
Constance L. Friedman
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
No Reduction ◽  
Renal Plasma Flow ◽  
Excretory Function ◽  
Small Doses ◽  
Cent Saline ◽  
Electrolyte Change ◽  
Desoxycorticosterone Acetate ◽  
Pellet Form

Small doses of DCA administered at intervals in pellet form are capable of raising the blood pressure, altering renal function, and changing the electrolyte pattern in the intact rat. The concomitant feeding of 1 per cent saline intensifies the process. The elevation in blood pressure occurs prior to demonstrable changes in renal excretory function. The alteration in renal function consists first of a reduction in CPAH with the maintenance of a normal filtration rate. Filtration fraction is elevated while there is no reduction in renal plasma flow per unit of tubular excretory tissue. Later, filtration is interfered with and renal ischemia occurs. The electrolyte change is characterized by a sustained fall in plasma K and Cl, a rise in plasma Na, an increase in the Na/Cl ratio, and finally an elevation of Na plus K. Plasma Ca is unaffected. These observations suggest the possible etiological significance of the adrenal cortex in some types of hypertension.

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