Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity

Abstract

. Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity. Am J Physiol Renal Physiol 285: F619-F628, 2003. First published June 10, 2003 10.1152 10. /ajprenal.00388. 2002 diet is known to induce or aggravate hypertension in animal models of hypertension and in humans. When Sprague-Dawley rats (n ϭ 60) are fed a moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half develop obesity [obesity prone (OP)] and mild hypertension, whereas the other half [obesity resistant (OR)] maintain body weight equivalent to a low-fat control (C) and are normotensive. The aim of this study was to test the effect of high-NaCl diets (2 and 4% NaCl) on the development of hypertension and obesity, oxidative stress, and renal function. Both 2 and 4% NaCl induced an early increase in systolic blood pressure of OP but not OR or C rats. High-salt intake induced an increase in the size and reduction in number of adipocytes, concomitant to a twofold increase in circulating leptin in OP rats. Aortic superoxide generation indicated a 2.8-fold increase in the OP high-salt vs. normalsalt groups, whereas urine isoprostanes were not significantly increased. Also, hydroxynonenal protein adducts in the kidney were highly increased in OP rats on 2 and 4% NaCl, indicating oxidative stress in the renal tissue. Urine albumin was increased threefold in the OP on 2% NaCl and fourfold in the same group on 4% NaCl vs. 0.8% NaCl. Kidney histology indicated a higher degree of glomerulosclerosis in OP rats on high-salt diets. In summary, high-salt diet accelerated the development but did not increase the severity of hypertension; high salt increased oxidative stress in the vasculature and kidney and induced kidney glomerulosclerosis and microalbuminuria. Also, the OP rats on high salt displayed adipocyte hypertrophy and increased leptin production.glomerulosclerosis; kidney; leptin; sodium dietary OBESITY IS A complex, multifactorial disease that is associated with essential hypertension in ϳ78% of men and ϳ65% of women, as indicated by the data from the Framingham Heart Study (25). Another important contributor to hypertension in humans is the excessive consumption of dietary salt, and epidemiological studies have demonstrated a significant but weak relation between salt intake and hypertension (32, 33). Some, but not all, interventional studies have shown that salt restriction may lower blood pressure (BP) (19,33). Some recent studies report correlation among hypertension, salt sensitivity, and insulin resistance in obese humans (38), whereas others fail to observe a significant relationship (8). Animal models of obesity, hypertension, and insulin resistance display differences with respect to salt sensitivity. In Zucker rats, there is a clear correlation between salt intake and the severity of hypertension (4, 47), whereas in chronic hyperinsulinemic Sprague-Dawley (SD) rats, hypertension is not salt sensitive, albeit a shift in pressure-natriuresis relationship was reported (2). One important cont...

Dietary Sodium, Adiposity, and Inflammation in Healthy Adolescents

“…31,32 Second, independent of energy intake, chronic salt overload induced adipocyte hypertrophy and increased mass of adipose depots and high plasma leptin concentration by enhancing the adipocyte insulin sensitivity for glucose uptake, the insulin-induced glucose metabolism, and lipogenic capacity of white adipose tissue in rats. 1,2,33 We also found that sodium intake was positively and independently associated with increased circulating levels of leptin. Leptin is one of the most important adipokines secreted by fat cells, with a variety of physiologic roles related to the control of metabolism, maintenance of energy homeostasis and body weight, inflammatory response, and urinary sodium excretion.…”

“…For instance, animal studies have shown that a high sodium diet increases adipose tissue mass and adipocyte size, and leptin production. 1,2 In humans, greater sodium consumption has been linked to higher body weight, 3,4 possibly due to sodium' s effect on fluid intake because high sodium intake is often accompanied by high consumption of energy-dense foods and sugarsweetened soft drinks. [5][6][7][8][9] However, this may not always be the case because other studies have reported a positive relationship between dietary sodium intake and obesity independent of energy intake and sugar-sweetened beverage consumption.…”

Is Cardiac Hypertrophy in Spontaneously Hypertensive Rats the Cause or the Consequence of Oxidative Stress?

“…Oxidative stress develops when the well-regulated balance between prooxidants and antioxidants becomes uncontrolled and tips in favor of pro-oxidants. Oxidative stress is a major contributor to the aging process (26) and appears to be a common feature of hypertensive disorders from diverse origins (9,(27)(28)(29). ROS have also been shown to be involved in cardiac hypertrophy induced by several stimuli, such as mechanical stretch, endothelin and angiotensin II (30).…”

Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia

“…[31][32][33] However, we found that MC4R (Ϫ/Ϫ) mice, which have most of the characteristics of the metabolic syndrome, including obesity, visceral adiposity, hyperleptinemia, and hyperinsulinemia, do not develop hypertension when fed an NSD or HSD. Moreover, arterial pressure in MC4R (Ϫ/Ϫ) mice failed to increase in response to an HSD despite Ϸ40% greater sodium intake (resulting from hyperphagia) when compared with WT mice.…”