The hypertriglyceridemic rat as a genetic model of hypertension and diabetes

Stolba, P; Dobešová, Z; Hušek, Petr; Opltová, H.; Zicha, Josef; Vrána, A.; Kuneš, Jaroslav

doi:10.1016/0024-3205(92)90482-5

Cited by 45 publications

(26 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consonant with the observation that BP correlated positively with hypertriglyceridemia in rats. 16 Other studies observed that high triglycerides are associated with arterial contraction, increased vascular tone, endothelial dysfunction, and changes in membrane ion transport. 16,17,30,31 A role for triglycerides in enhancing pressor reactivity is also supported by our observation that infusions of Intralipid alone and with heparin in study 2 had comparable effects on plasma triglycerides and PD 20PE values despite significant differences in plasma NEFAs.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Intralipid Enhances α ₁ -Adrenergic Receptor–Mediated Pressor Sensitivity

et al. 1998

View full text Add to dashboard Cite

Abstract-The dyslipidemia in obese hypertensive persons may contribute to their increased vascular ␣-adrenergic receptor reactivity and tone. To further examine this notion, we conducted 2 studies of pressor sensitivity to phenylephrine, an ␣ 1 -adrenergic receptor agonist, in lean normotensive subjects. In the first study (nϭ6), pressor responses to phenylephrine were obtained before and during a saline and heparin infusion. On another day, pressor reactivity to phenylephrine was measured before and during infusion of 20% Intralipid at 0.5 mL ⅐ m Ϫ2 ⅐ min Ϫ1 with heparin at 1000 U/h to increase lipoprotein lipase activity and raise nonesterified fatty acids (NEFAs). In the second study (nϭ8), baseline reactivity to phenylephrine was obtained on 2 separate days and repeated after raising NEFAs and triglycerides either with 0.8 mL ⅐ m Ϫ2 ⅐ min Ϫ1 of 20% Intralipid alone or together with heparin. The infusion of saline and heparin did not significantly change plasma NEFAs from baseline (516Ϯ90 versus 512Ϯ108 mol/L, respectively; PϭNS) or the dose of phenylephrine required to raise mean blood pressure by 20 mm Hg ([PD 20PE ]; 1.00Ϯ0.14 versus 0.95Ϯ0.10 Across all study conditions, changes in levels of triglycerides and NEFAs correlated with changes in mean arterial pressure responses to phenylephrine, especially at the 0.4-g ⅐ kg Ϫ1 ⅐ min Ϫ1 infusion rate of phenylephrine (rϭ0.64, PϽ0.01 and rϭ0.54, PϽ0.01, respectively). These data suggest that raising levels of plasma NEFAs and/or triglycerides enhances ␣ 1 -adrenoceptor-mediated pressor sensitivity. The findings suggest that lipid abnormalities in obese hypertensives, which include elevated NEFAs and triglycerides, contribute to greater vascular ␣ 1 -adrenergic reactivity. (Hypertension. 1998;32:693-698.) Key Words: fatty acids Ⅲ phenylephrine Ⅲ receptors, adrenergic Ⅲ blood pressure I nsulin resistance is associated with a cluster of cardiovascular risk factors including hypertension, but the intermediary mechanisms linking metabolic and hemodynamic abnormalities are not well defined.1-7 Abdominally obese hypertensive persons have increased vascular ␣-adrenergic tone and reactivity, 8 as well as increased plasma concentrations 9 and turnover of nonesterified fatty acids (NEFAs) that are highly resistant to suppression by insulin.10 Evidence implicates abnormalities of NEFAs as one potential pathogenetic link between abdominal obesity and hypertension. 3,9 -12 We observed a positive correlation between plasma fatty acids during euglycemic clamp and blood pressure (BP) in obese subjects that was independent of hyperinsulinemia and insulin-mediated glucose disposal. 10 In minipigs, raising fatty acid levels increases systemic vascular resistance and BP. 13Our previous research has shown that raising fatty acids in the dorsal hand vein of normal volunteers to concentrations observed in obese hypertensives significantly increases venoconstrictor responses to phenylephrine as well as a neuroreflex stimulus.11,14 These observations raise the possibility that the e...

show abstract

Section: Discussionmentioning

confidence: 99%

“…In contrast, changes of NEFAs no longer correlated significantly with changes of mean arterial pressure after controlling for the change in triglycerides (partial rϭ0. 16…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intralipid Enhances α ₁ -Adrenergic Receptor–Mediated Pressor Sensitivity

et al. 1998

View full text Add to dashboard Cite

show abstract

“…101 In contrast, HTG rats, which were selected from Wistar rats for high plasma triglycerides, 102 were also found to be hypertensive. 103 Our recent study 104 compared Na ϩ transport in erythrocytes of the two rat models of genetic hypertension accompanied by dyslipidemia. Both HTG and LH rats had elevated plasma triglycerides, whereas plasma total cholesterol was increased in LH rats but decreased in HTG animals.…”

mentioning

confidence: 99%

Abnormalities of membrane function and lipid metabolism in hypertension A review

Zicha

Kuneš

Devynck

1999

American Journal of Hypertension

211

175

View full text Add to dashboard Cite

Hypertension, which is characterized by multiple alterations in the structure and function of the cell membrane, is often associated with important metabolic abnormalities including those concerning lipid metabolism. Dyslipidemia accompanying essential hypertension consists of elevated plasma triglycerides, low HDL cholesterol, and increased levels of atherogenic LDL cholesterol particles. The altered membrane microviscosity seen in hypertensive subjects reflects the changes of membrane lipid composition resulting from intensive exchange between circulating and membrane lipids, as well as from abnormal cellular lipid synthesis and metabolism. The changes of membrane microviscosity are known to modulate the activity of proteins involved in ion transport, signal transduction, cell Ca 2؉ handling, intracellular pH regulation, etc. Alterations in plasma or membrane lipids are indeed closely associated with ion transport abnormalities as well as with impaired control of cytosolic Ca 2؉ T here is no doubt that essential hypertension is associated with multiple membrane alterations, including changes in membrane microviscosity, receptor function, signal transduction, ion transport, calcium mobilization, intracellular pH regulation, and so on. Lipids, as an integral part of the cell membrane, play a decisive role in the modulation of the membrane properties mentioned. Specific lipid-lipid and lipid-protein interactions result in a highly dynamic but precisely controlled architecture of membrane components. Major regulators of membrane architecture are membrane potential, intracellular Ca 2ϩ and pH, lipid composition, cell-to-cell contact, and membrane coupling with the cytoskeleton or extracellular matrix. Intermolecular associations in the membrane and at the membrane-cytoskeleton interface are further selectively controlled by specific phosphorylation and dephosphorylation cascades involving both proteins and lipids. This is regulated by the extracellular matrix as well as by the binding of growth factors and hormones to their specific receptors. 1,2The aim of this review is to outline some interrelationships between abnormal lipid metabolism and altered membrane structure or function in human and experimental hypertension, and to evaluate whether abnormal lipid metabolism, which is responsible for a great part of membrane abnormalities found in hypertension, might be an integral part of its pathogenetic mechanisms. BLOOD PRESSUREMultiple metabolic abnormalities often accompany essential hypertension. Decreased high-density lipoproteins (HDL) together with increased plasma levels of low-density (LDL) and very low-density lipoproteins (VLDL), as well as hypertriglyceridemia, hypercholesterolemia, and insulin resistance, were found in many hypertensive patients. 3,4 There is increasing evidence for a genetic basis for the association of hypertension with insulin resistance and dyslipidemia. The genetic locus associated with dyslipidemia accompanying hypertension or diabetes seems to be closely linked to the LDL recept...

show abstract

“…They suffer from hypertriglyceridemia, insulin resistance and hypertension 3 . Our pilot experiments revealed an increased activity and expression of 11HSD1 in the liver of female HHTg rats.…”

mentioning

confidence: 99%

Occurrence of Lipids in the Liver of the Hypertriglyceridemic Rats

Zemanová¹,

Strnadova²,

Jirsová³

et al. 2009

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Aims:The purpose of this study was to demonstrate the accumulation and distribution of lipids in the liver of the adult Prague hereditary hypertriglyceridemic (HHTg) rats. They reveal an increased expression of 11β-hydroxysteroid dehydrogenase 1 (11HSD1), which locally increases concentration of corticosterone in the liver. We studied the effect of the 11HSD1 inhibition on the lipid content.Methods: Samples of liver of three groups of adult female rats -HHTg, HHTg treated for 14 days with 50 mg/kg/day carbenoxolone (HHTg+CBX) and control Wistar rats, were examined histochemically. Cryosections of the samples were stained with Oil red O or Sudan black B to demonstrate different kinds of lipids. Extent and intensity of staining was evaluated semiquantitatively.Results: The orientational analysis showed a higher extent and intensity of the staining of the liver of HHTg and HHTg+CBX rats (equal in both hypertriglyceridemic groups) than that of the control Wistar rats. Oil red O stained unsaturated fatty acids and neutral fats, mainly triglycerides. The difference was on average 30 per cent. Staining of phospholipids with Sudan black B showed similarly the higher positivity in the hypertriglyceridemic groups than in controls.Conclusions: Staining for triglycerides and phospholipids demonstrated a higher amount of lipids in the liver of HHTg and HHTg+CBX female rats than in controls. The inhibition of 11HSD1 activity had no effect on the lipid content in the liver of the HHTg rats.

show abstract

The hypertriglyceridemic rat as a genetic model of hypertension and diabetes

Cited by 45 publications

References 23 publications

Intralipid Enhances α ₁ -Adrenergic Receptor–Mediated Pressor Sensitivity

Intralipid Enhances α ₁ -Adrenergic Receptor–Mediated Pressor Sensitivity

Abnormalities of membrane function and lipid metabolism in hypertension A review

Occurrence of Lipids in the Liver of the Hypertriglyceridemic Rats

Contact Info

Product

Resources

About

The hypertriglyceridemic rat as a genetic model of hypertension and diabetes

Cited by 45 publications

References 23 publications

Intralipid Enhances α 1 -Adrenergic Receptor–Mediated Pressor Sensitivity

Intralipid Enhances α 1 -Adrenergic Receptor–Mediated Pressor Sensitivity

Abnormalities of membrane function and lipid metabolism in hypertension A review

Occurrence of Lipids in the Liver of the Hypertriglyceridemic Rats

Contact Info

Product

Resources

About

Intralipid Enhances α ₁ -Adrenergic Receptor–Mediated Pressor Sensitivity

Intralipid Enhances α ₁ -Adrenergic Receptor–Mediated Pressor Sensitivity