Ion transport in hypertension: are changes in the cell membrane responsible?

Bing, R. F.; Heagerty, Anthony M.; Thurston, H.; Swales, J. D.

doi:10.1042/cs0710225

Cited by 48 publications

(14 citation statements)

References 19 publications

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“…Future studies should include actual quantitation of changes in RBC and platelet membrane cholesterol content, C/P ratios, and microviscosity during treatment with lipid-altering drugs to help clarify the relation between membrane composition and cation transport. At present, however, based on the evidence in the current study, we cannot support the contention of Bing et al 8 that "Changes in cell membrane lipid composition provide an explanation . .…”

Section: Discussioncontrasting

confidence: 54%

“…8 However, it is equally plausible that high total or low HDL cholesterol and hypertension are both features of a common underlying defect, such as that which may cause the syndrome characterized by Williams et al 9 as familial dyslipidemic hypertension. If an increased V,^ for RBC Li + -Na + countertransport is a marker for a genetic predisposition to familial dyslipidemic hypertension or related hypercholesterolemia syndromes, 10 then increased RBC Li + -Na + countertransport, hyperlipidemia, and hypertension could all be interrelated, but lipid levels per se would not necessarily contribute to elevated RBC Li + -Na + countertransport activity.…”

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confidence: 99%

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Effects of lovastatin treatment on red blood cell and platelet cation transport.

et al. 1991

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Hypercholesterolemia frequently accompanies hypertension, and it has been suggested that by affecting membrane lipid composition, hypercholesterolemia may cause or accentuate abnormalities in several red blood cell transports associated with hypertension. Such an effect might obfuscate the relation of membrane markers to hypertension and decrease their usefulness in genetic studies of the heritable basis of hypertension. To determine if changing plasma lipids affects membrane transport, we studied the effects of the cholesterol-lowering agent lovastatin on red blood cell lithium-sodium countertransport and sodium-potassium-chloride cotransport, red blood cell sodium and water content, and platelet amiloride-sensitive volume responsiveness to cytoplasmic acidification, an indirect measure of sodium-proton exchange that has been proposed as a new membrane marker for hypertension. In a 24 -week, placebo-controlled, double-blinded, randomized trial, lovastatin significantly lowered total and low density lipoprotein cholesterol and raised high density lipoprotein cholesterol. Red blood cell lithium-sodium countertransport and sodium-potassium-chloride cotransport were not significantly altered. Red blood cell sodium content decreased significantly in the lovastatintreated group, probably as a result of an increase in red blood cell sodium-potassium pump activity. Platelet amiloride-sensitive responses to cytoplasmic acidification were significantly depressed by lovastatin treatment, suggesting that lowering plasma cholesterol may suppress platelet sodium-proton exchange. It has been hypothesized that the hypeiiipidemias frequently observed in essential hypertensive patients may alter membrane lipid composition and affect membrane cation transport activities. Our observations on the effects of lovastatin treatment suggest that the abnormalities in lithium-sodium countertransport and sodium-potassiumchloride cotransport associated with human essential hypertension are unlikely to result from altered membrane cholesterol content or membrane cholesterol/phospholipid ratio. Altered membrane lipid composition may affect the sodium-potassium pump or sodium-proton antiport. olism cause or at least contribute to the increased Vnu,, for RBC Li + -Na + countertransport in hypertension.8 However, it is equally plausible that high total or low HDL cholesterol and hypertension are both features of a common underlying defect, such as that which may cause the syndrome characterized by Williams et al 9 as familial dyslipidemic hypertension. If an increased V,^ for RBC Li + -Na + countertransport is a marker for a genetic predisposition to familial dyslipidemic hypertension or related hypercholesterolemia syndromes, 10 then increased RBC Li + -Na + countertransport, hyperlipidemia, and hypertension could all be interrelated, but lipid levels per se would not necessarily contribute to elevated RBC Li + -Na + countertransport activity.We measured RBC Li + -Na + countertransport activity and plasma lipid levels in patients before and aft...

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Section: Discussioncontrasting

confidence: 54%

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confidence: 99%

Effects of lovastatin treatment on red blood cell and platelet cation transport.

et al. 1991

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“…Although we did not investigate changes in fluidity, it is known to modify enzyme activity as well as other biochemical and physiological functions such as ion transport, 29,30 which are important determinants of membrane potential in VSMC. When rings were contracted by depolarizing them with high extracellular concentrations of KCl, linoleic acid failed to induce relaxation, suggesting that the vasorelaxant effects of linoleic acid may be mediated by changes in membrane potential.…”

Section: Discussionmentioning

confidence: 99%

Linoleic Acid Induces Relaxation and Hyperpolarization of the Pig Coronary Artery

et al. 1998

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Abstract-Linoleic acid, a polyunsaturated C 18 fatty acid, is one of the major fatty acids in the coronary arterial wall. Although diets rich in linoleic acid reduce blood pressure and prevent coronary artery disease in both humans and animals, very little is known about its mechanism of action. We believed that its beneficial effects might be mediated by changes in vascular tone. We investigated whether linoleic acid induces relaxation of porcine coronary artery rings and the mechanism involved in this process. Linoleic acid and two of its metabolites, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-hydroperoxyoctadecadienoic acid (13-HPODE), induced dose-dependent relaxation of prostaglandin (PG) F 2␣ -precontracted rings that was not affected by indomethacin (10 Ϫ5 mol/L), a cyclooxygenase inhibitor, or cinnamyl-3,4-dihydroxy-␣-cyanocinnamate (CDC; 10 Ϫ5 mol/L), a lipoxygenase inhibitor. Removal of endothelial cells had no effect on vasorelaxation, suggesting a direct effect on the vascular smooth muscle cells (VSMC). When rings were contracted with KCl, linoleic acid failed to induce relaxation. Although tetrabutylammonium (5ϫ10 Ϫ3 mol/L), a nonselective K ϩ channel blocker, slightly inhibited the relaxation caused by linoleic acid, glibenclamide (10 Ϫ6 mol/L), an ATP-sensitive K ϩ channel blocker, and charybdotoxin (7.5ϫ10-activated K ϩ channel blockers, had no effect. However, relaxation was completely blocked by ouabain (5ϫ10 Ϫ7 mol/L), a NaIn addition, linoleic acid (10 Ϫ6 mol/L) caused sustained hyperpolarization of porcine coronary VSMC (from -49.5Ϯ2.0 to -60.7Ϯ4.2 mV), which was also abolished by ouabain. We concluded that linoleic acid induces relaxation and hyperpolarization of porcine coronary VSMC via a mechanism that involves activation of the Na Key Words: linoleic acid Ⅲ nitric oxide Ⅲ prostaglandins Ⅲ endothelium-derived hyperpolarizing factorinoleic acid, a polyunsaturated C 18 fatty acid (18:2n-6), is one of the main essential fatty acids, and is one of the major fatty acids in the arterial wall, 1 which can be liberated by phospholipase activity.2,3 Linoleic acid is the principal precursor of arachidonic acid (20:4n-6), which is the substrate for synthesis of prostaglandins and thromboxane A 2 . Structurally related derivatives of arachidonic acid and linoleic acid have been demonstrated in blood vessels and related tissues. Linoleic acid can be enzymatically or nonenzymatically 4 converted to 13-HPODE, which can be further reduced to 13-HODE. Production of these hydro(per)oxy metabolites has been reported in aortas from rats, rabbits, and cows, 1 and unlike the fetal calf aorta 5 their formation is independent of cyclooxygenase activity. Lipoxygenation of linoleic acid resulted in 13-HODE formation in endothelial cells.6 Linoleic acid metabolites are formed in larger quantities than the corresponding arachidonic acid metabolites, 1 suggesting that they may be of biological significance.Several studies have suggested that hypertension and cardiovascular disease are caused in part by a relat...

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“…28 Identification of which membrane lipids and what protein-lipid interactions may be involved is beyond the scope of the present investigation.…”

Section: -24mentioning

confidence: 99%

Sodium-lithium countertransport and hypertension in Rochester, Minnesota.

Turner

Michels

1991

Hypertension

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The objectives of the present study were to determine whether increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and to determine whether this association is independent of the effects of gender, age, body size, and plasma lipids. We studied 543 men and 589 women from the population of Rochester, Minnesota. Mean sodium-lithium countertransport was higher in hypertensive than in normotensive subjects in men (370±147 [mean±SD] versus 315±110 jtmol/1 red blood cells [RBC]/hr, p<0.001) and in women (339±114 versus 269±92 fimol/l RBC/hr, /><0.001). Interindividual differences in plasma triglycerides, body mass index (wt/[ht]2 ), and plasma total cholesterol explained 13.0% of sodium-lithium countertransport variation in men (/><0.001) and 20.2% in women (/><0.001). Age did not predict additional sodium-lithium countertransport variation in either gender. Slopes of the regressions of sodium-lithium countertransport on plasma triglycerides, body mass index, and plasma total cholesterol did not differ between diagnostic groups in men (p=03l) or in women (p=0J29). After adjustment to remove sodium-lithium countertransport variation attributable to these covariates, mean sodium-lithium countertransport remained significantly higher in hypertensive than in normotensive subjects in men (354±139 versus 319±104 /i.mol/1 RBC/hr, p<0.01) and in women (311 ±103 versus 278±83 /imol/1 RBC/hr, p<0.01). These findings in a large sample from Rochester, Minnesota, support the conclusions that increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and that this association is independent of the effects of gender, age, body size, and plasma lipids. Additional studies are necessary to establish whether sodium-lithium countertransport is an independent predictor of risk of developing essential hypertension. {Hypertension 1991;18:183-190) S odium-lithium countertransport has been proposed as an indicator of inherited predisposition to essential hypertension. This proposal is based on the finding of higher mean sodium-lithium countertransport in Caucasian patients with hypertension and in their young, hypertensive-prone offspring than in selected normotensive controls.1 However, since the samples for most previous studies were small and were ascertained through referral clinics or hospitals, their findings may not be representative of the community at large. Furthermore, many characteristics other than blood pressure differ between hypertensive and normotensive individuals, and some of these vari-

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Ion transport in hypertension: are changes in the cell membrane responsible?

Cited by 48 publications

References 19 publications

Effects of lovastatin treatment on red blood cell and platelet cation transport.

Effects of lovastatin treatment on red blood cell and platelet cation transport.

Linoleic Acid Induces Relaxation and Hyperpolarization of the Pig Coronary Artery

Sodium-lithium countertransport and hypertension in Rochester, Minnesota.

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