Arterial hypertension and hyperlipidemia as determinants of glomerulosclerosis

Gröne, Hermann Josef; Walli, Autar K.; Gröne, Elisabeth F.

doi:10.1007/bf00190332

Cited by 19 publications

(7 citation statements)

References 34 publications

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“…However, local (or tissue) production and activity of angiotensin II cannot be excluded. Moreover, coexistence of experimental HC and HT has been previously demonstrated to induce or accelerate atherosclerotic changes in the kidney 9,29,30 and the rat aorta. 31,32 Our study confirms these findings and demonstrates that the combination of HC and HT is associated with alterations in arterial wall structure.…”

Section: Discussionmentioning

confidence: 98%

Hypercholesterolemia and Hypertension Have Synergistic Deleterious Effects on Coronary Endothelial Function

Rodriguez-Porcel

Lerman

Herrmann

et al. 2003

ATVB

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Objective-Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function. Methods and Results-Four groups of pigs were studied after 12 weeks of a normal diet (nϭ9), a 2% HC diet (nϭ9), HT (achieved by unilateral renal artery stenosis, nϭ8), or HCϩHT (nϭ6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HCϩHT compared with each risk factor alone (PϽ0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (PϽ0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity. Conclusions-These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist. Key Words: animal models Ⅲ coronary circulation Ⅲ oxidant stress Ⅲ risk factors A therosclerosis-related coronary disease, in its early stages, is characterized by coronary endothelial dysfunction, potentially leading to an increased incidence of cardiac events. 1 Hypercholesterolemia (HC) and hypertension (HT) are major risk factors for atherosclerosis, and their combination is associated with a yet greater increase in the incidence of cardiac events. 2 Thus, it becomes increasingly important to understand the pathogenic mechanisms of their interaction. Individually, both diet-induced HC 3 and HT 4,5 have been associated with abnormalities in coronary endothelial function. Although the effect of each risk factor has been studied individually, whether their coexistence has a synergistic deleterious effect on coronary endothelial function remains poorly understood.One of the mechanisms that might be activated in both HC 6,7 and HT 8 and might hinder coronary vascular function is a shift in scavenging activity and redox status, a state known as increased oxidative stress. Increased vascular oxidative stress can be characterized by increased production of reactive oxygen species (ROS) and pro-oxidant reactions 8,9 and decreased levels of endogenous antioxidants 7 and endogenous radical scavenger systems, 7 as well as an increase in oxidazibility, which might also impair vascular function. 10,11 Furthermore, increased oxidative stress can also have deleterious effects on other pathways, such as the nitric oxide (NO) pathway. 12,13 Thus, these...

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Section: Discussionmentioning

confidence: 98%

Hypercholesterolemia and Hypertension Have Synergistic Deleterious Effects on Coronary Endothelial Function

Rodriguez-Porcel

Lerman

Herrmann

et al. 2003

ATVB

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“…HC and HT are major risk factors for the development of end-stage renal disease 3 and are commonly present in combination. 4 Long-standing HT induces vascular and glomerular damage, including arteriolosclerosis and glomerulosclerosis, 22,23 with a progressive decline in renal function. Dyslipidemias, with subsequent lipid deposits and inflammatory infiltration, can similarly injure intrarenal vascular and glomerular structures.…”

Section: Discussionmentioning

confidence: 99%

Combination of Hypercholesterolemia and Hypertension Augments Renal Function Abnormalities

et al. 2001

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Abstract-Hypercholesterolemia and hypertension are both risk factors for end-stage renal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hemodynamics and function in response to vasoactive challenges with acetylcholine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (nϭ10) or hypercholesterolemic (nϭ10) diet, renovascular hypertension (nϭ7), or combined hypercholesterolemiaϩhypertension (nϭ6). The hypercholesterolemic and hypercholesterolemicϩhypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemicϩhypertensive groups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filtration rates were similar among the groups. In response to acetylcholine, cortical perfusion increased in normal animals (15.6Ϯ4.7%, Pϭ0.002) but not in hypercholesterolemic or hypertensive animals (8.0Ϯ7.4% and 8.2Ϯ5.9%, respectively; PϾ0.05). Moreover, in the hypercholesterolemicϩhypertensive group, cortical perfusion response was further attenuated (2.5Ϯ4.8%, Pϭ0.02) and significantly different from the group fed a normal diet (PϽ0.05). The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemicϩhypertensive group. The functional abnormalities in hypercholesterolemia or hypertension were associated with a decrease in systemic and/or renal tissue levels of oxygen radical scavengers that was again accentuated in hypercholesterolemiaϩhypertension. These results demonstrate that concurrent hypercholesterolemia and hypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially augment renal functional impairment and play a role in the initiation and progression of renal injury in hypertension and atherosclerosis. Clinical studies have shown that the coexistence of dyslipidemia and HT greatly increases the incidence of cardiovascular morbidity and mortality 4 and likely modulates the deterioration of renal function as well. 5 Indeed, both antihypertensive and lipid-lowering therapies can halt the progression of renovascular disease and contribute to the preservation of renal function. 6 The onset of renal injury is detectable after a relatively short exposure to cardiovascular risk factors, inasmuch as experimental HC and HT have each been linked to alterations of vascular and tubular function. We have previously shown that experimental HC was associated with alterations in the renal vascular response to challenge both in vivo 7 and in vitro 8 and abnormal tubular dynamics in vivo. 7 Similarly, HT has been shown to induce abnormalities of renal vascular 9 and tubular 10 function. One of the mechanisms...

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confidence: 99%

“…14 In addition, hyperlipidemia associated with hypertension may induce glomerulosclerosis in the kidney and eventually alter kidney function. 15 There also are data that indicate increased oxidative stress in human essential hypertension, 16,17 as well as in obese hypertensive patients, 18 that may further contribute to the development of atherosclerosis or other cardiovascular diseases.…”

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confidence: 99%

Development of Hypertension in a Rat Model of Diet-Induced Obesity

et al. 2000

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Abstract-Although obesity is a risk factor for hypertension, the relationship between these 2 conditions is not well understood. Therefore, we examined some parameters of hypertension and cardiovascular disease in a dietary model of obesity. Male Sprague-Dawley rats were provided either a control diet (C) or a diet containing 32% kcal as fat (similar to a Western diet) for 1, 3, or 10 weeks. Rats in the latter group diverged based on body weight gain into obesity-prone (OP) and obesity-resistant (OR) groups. Systolic blood pressure in OP rats was significantly higher after 10 weeks of the diet (149Ϯ4.8 mm Hg) compared with both OR and C groups (131Ϯ3.7 and 129Ϯ4.5 mm Hg, respectively). The aortic wall area of OP rats was significantly increased, indicating arterial hypertrophy, and a 2-fold increase in plasma renin activity was found in OP rats compared with OR and C rats. The lipid profile showed a significant increase in plasma and VLDL triglycerides of OP versus OR and C groups as early as 3 weeks on the diet. Plasma and LDL-cholesterol levels were increased in the OP group versus the OR and C groups after 3 weeks of the diet, but the difference was blunted after 10 weeks. Lipid peroxidation (thiobarbituric acid-reactive substances) in OP rats was increased 2-fold in LDL and 1.5-fold in aortic wall compared with OR rats, suggesting an increased oxidative stress in these animals. Periodic acid-Schiff staining of the kidney showed mesangial expansion and focal sclerosis that were more prominent in OP rats than in OR rats. The results suggest that hypercholesterolemia, but not hypertriglyceridemia, is linked to the diet; that hypertension and renin-angiotensin system activation are associated with obesity; and that lipid peroxidation and renal damage are the results of both factors. (Hypertension. 2000;35:1009-1015.)besity is a complex, multifactorial disease that is often associated with diabetes, cardiovascular diseases, and stroke. Among other factors, obesity is an important contributor to essential hypertension in humans. Data from the Framingham Heart Study suggest that Ϸ78% of essential hypertension in men and Ϸ65% of essential hypertension in women can be directly attributed to obesity. 1 However, the mechanisms that link obesity with high blood pressure and altered renal function have not been fully elucidated. One problem in the study of the mechanisms of obesity hypertension has been the lack of a suitable animal model. The ideal model would not only have the features of human hypertension but also allow the study of sequential changes in cardiovascular and kidney function that occur with weight gain. The genetic models of obesity may or may not develop hypertension or do not mimic the changes observed in humans. For example, Zucker rats have decreased plasma renin activity (PRA) 2 as opposed to the high PRA observed in humans. 3 In contrast, diet-induced obese animal models appear to be the most relevant with regard to human obesity. Some of these models, such as the obese dog 4 or obese rabbit 5 fed...

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Arterial hypertension and hyperlipidemia as determinants of glomerulosclerosis

Cited by 19 publications

References 34 publications

Hypercholesterolemia and Hypertension Have Synergistic Deleterious Effects on Coronary Endothelial Function

Hypercholesterolemia and Hypertension Have Synergistic Deleterious Effects on Coronary Endothelial Function

Combination of Hypercholesterolemia and Hypertension Augments Renal Function Abnormalities

Development of Hypertension in a Rat Model of Diet-Induced Obesity

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