Mechanism of hypertriglyceridemia in Dahl rats.

Abstract

Plasma triglyceride concentrations were shown to be higher in hypertensive (153±2 mm Hg) male Dahl salt-sensitive rats than in control Sprague-Dawley rats (122 ±2 mm Hg). These differences in triglyceride concentrations were seen when blood was drawn at 9 AM from unfasted animals (229±27 versus 111±8 mg/dL), at 1 PM after a 4-hour fast (186±13 versus 88±4 mg/dL), or at 9 AM after a 13-hour fast (151±6 versus 90±6 mg/dL), all p<0.001. Total triglyceride secretion was also compared in groups of rats by determining the increment in plasma triglyceride concentration for 2 hours after blocking triglyceride removal from plasma by injecting Triton. Studies performed at 1 PM and 9 AM, after the 4-and 13-hour fast, demonstrated that total triglyceride secretion was greater (p<0.05) in Dahl rats only when studied at 1 PM. Direct estimates of hepatic triglyceride secretion at 1 PM also demonstrated a significant (p<0.02) increase in secretion rate by perfused livers from Dahl rats, due in part to their increased liver size. In addition, removal of prelabeled very low density lipoprotein-triglyceride in the intact rat was significantly (p<0.05) decreased in Dahl rats. Lipoprotein lipase activity measured in skeletal muscle, heart, and adipose tissue was also significantly decreased at 9 AM and 1 PM (after 0 and 4 hours of fasting) in tissue from Dahl rats. These data confirm that Dahl rats have higher plasma triglyceride concentrations than Sprague-Dawley rats. Since both total and hepatic triglyceride secretion were somewhat greater in Dahl rats, in association with a decrease in both removal of very low density lipoprotein from plasma and decreased muscle and adipose tissue lipoprotein lipase activity, it seems likely that hypertriglyceridemia in Dahl rats results from a combination of increased triglyceride secretion and decreased triglyceride removal. 1 Since hypertriglyceridemia has also been noted in patients with hypertension, 23 as well as in two other models of rodent hypertension, 45 it seemed possible that an increased understanding of the cause of hypertriglyceridemia in a rodent model of hypertension would provide useful information relevant to the change in lipoprotein metabolism seen in patients with high blood pressure. As a first step in this process, we initiated a series of studies to define the mechanism of hypertriglyceridemia in Dahl S rats. Increased plasma very low density lipoprotein-TG (VLDL-TG) concentration in Dahl S rats may be due to increased hepatic VLDL-TG secretion, decreased VLDL-TG removal, or both, with the latter process dependent on the activity of lipoprotein lipase (LPL). 6 We determined TG secretion in both the intact

Rat Chromosome 8 Confers Protection against Dyslipidemia Caused by a High-Fat/ Low-Carbohydrate Diet

“…The authors suggest the activation of lipoprotein lipase in white adipose tissue as a potential cause of the apparent disconnect between plasma triglycerides and increased triglyceride secretion. Conclusions put forth by Sato et al [47] are consistent with increased hepatic triglyceride secretion and decreased removal of plasma triglycerides observed in Dahl salt-sensitive rats [48] and increased production and reduced clearance of very low density lipoprotein particles in humans (see [28]. The scope of our study is not sufficient to elucidate the disconnect between fat pad weight and plasma levels of triglycerides, but the genes associated with metabolism, lipogenesis and accumulation of lipoproteins may be located on SSBN8.…”

Streptozotocin-Induced Diabetes Enhances Cardiac Heparin-Releasable Lipoprotein Lipase Activity in Spontaneously Hypertensive Rats

“…During hypertension, LPL activity is reduced in skeletal muscle and adipose tissue in human patients 32,33 and in Dahl saltsensitive rats. 34 We recently reported that the heparin-releasable LPL fraction in SHR hearts is reduced relative to that of WKY rats. 22 Because nifedipine and CGS-21680, vasodilators with divergent mechanisms of action, normalized enzyme release, we concluded that flow through coronary blood vessels might influence LPL activity.…”

Calcineurin Inhibitor Attenuates the Development and Induces the Regression of Cardiac Hypertrophy in Rats With Salt-Sensitive Hypertension

“…They show rapid onset of hypertension without variation among animals and develop both pressure-overload-and volume-overloadinduced cardiac hypertrophy only when fed a high salt diet. 14 -16 DS rats show not only salt-sensitive hypertension but also hypertriglyceridemia and hyperinsulinemia, 21,22 suggesting that DS rats have some features similar to human hypertension. It has also been reported that expression levels of interleukin-1␤ and monocyte chemoattrac-tant protein-1 are increased in the left ventricle of DS rats.…”