diphenylhexatriene and Hypertension

To determine the relationships between blood pressure, membrane microviscosity, plasma lipids and cytosolic pH in Dahl rats susceptible or resistant to salt hypertension.. Blood pressure, plasma triglycerides and total cholesterol, platelet cytosolic pH (pHi) and the microviscosity of both outer membrane leaflet (TMA-DPH fluorescence anisotropy) and membrane lipid core (DPH fluorescence anisotropy) were studied in platelets and erythrocyte ghosts of Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats fed either a low-salt diet (0.3% NaCl) until the age of 9, 15 or 24 weeks or a high-salt diet (4% NaCl) for 5 or 10 weeks after weaning.. At low salt intake, DPH but not TMA-DPH anisotropy increased with age in platelets of SS/Jr rats. Chronic high salt intake was accompanied by an increase of DPH anisotropy in platelets but not in erythrocyte ghosts of SS/Jr rats. Platelet DPH anisotropy correlated positively with blood pressure of salt-loaded SS/Jr rats. Chronic high salt intake also reduced pHi in platelets, the regulation of which seemed to be related to the changes in TMA-DPH anisotropy. This especially concerns the thrombin-induced pHi rise which was inversely related to basal pHi, plasma lipids and TMA-DPH anisotropy. Altered membrane lipid composition might be the underlying mechanism because both membrane microviscosity and platelet pHi regulation were reported to correlate significantly with plasma triglycerides and/or cholesterol.. Platelets of salt hypertensive Dahl rats are characterized by an increased microviscosity of membrane lipid core which correlated positively with blood pressure. The major influence of plasma triglycerides on DPH anisotropy should be taken into consideration when investigating the links between membrane microviscosity and blood pressure. On the other hand, the changes in microviscosity of the outer membrane leaflet might be involved in pHi regulation (probably through control of the Na+/H+ exchanger).

Topics: Animal Feed; Animals; Blood Platelets; Blood Pressure; Blood Viscosity; Cytosol; Diphenylhexatriene; Erythrocyte Membrane; Fluorescent Dyes; Follow-Up Studies; Hydrogen-Ion Concentration; Hypertension; Lipids; Male; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Sodium-Hydrogen Exchangers

To study membrane viscosity in various rat strains with genetic forms of experimental hypertension.. The relationship between blood pressure and membrane dynamics was investigated in erythrocytes from three different rat strains with experimental hypertension, namely two models of salt-induced hypertension (Sabra and Dahl rats) and Lyon hypertensive rats with spontaneous hypertension.. Membrane microviscosity was evaluated by diphenylhexatriene and trimethylamino-diphenylhexatriene fluorescence steady-state anisotropy.. There were no significant differences among particular experimental groups in trimethylamino-diphenylhexatriene anisotropy that reflect microviscosity changes at the water-lipid interface of the external membrane leaflet. In contrast, the diphenylhexatriene anisotropy, which is related to the core membrane microviscosity, was significantly reduced in the Dahl salt-sensitive rats (irrespective of salt intake level) and in the Sabra hypertension-prone rats with developed salt hypertension. Erythrocyte membranes of Lyon hypertensive rats also had lower values of diphenylhexatriene anisotropy than the respective normotensive controls but this difference was not statistically significant.. Systolic (and often also diastolic) blood pressure correlated negatively with the diphenylhexatriene anisotropy in each of the three strains studied, whereas the trimethylamino-diphenylhexatriene anisotropy of the erythrocyte membranes had no significant relationship to the blood pressure. Further experiments should clarify whether the observed relationship of the diphenylhexatriene anisotropy to blood pressure reflects true pathogenetic mechanisms or is a consequence of haemodynamic changes.

Topics: Animals; Blood Pressure; Diphenylhexatriene; Disease Models, Animal; Erythrocyte Membrane; Fluorescence Polarization; Fluorescent Dyes; Hypertension; In Vitro Techniques; Male; Membrane Fluidity; Rats; Rats, Inbred Strains; Sodium Chloride; Viscosity

1. To evaluate the response of red blood cells subjected to the shear flow in hypertension, the relationships between wall shear phenomena determined in vivo in the brachial artery of hypertensive patients and the modifications of the membrane dynamics measured in vitro in erythrocyte ghosts of 32 patients were investigated. 2. Two fluorescent probes, diphenylhexatriene (DPH) and its trimethylamino-derivative (TMA-DPH), localized respectively in the lipid membrane core and at the lipid-water interface, were used. 3. Shear rate, shear stress and blood velocity were positively correlated with TMA-DPH anisotropy (P = 0.015, 0.005 and 0.026, respectively), but not with that of DPH. This indicates that wall shear forces were associated with the microviscosity of the outer part of the cell membrane. 4. The changes in wall shear forces and erythrocyte membrane microviscosity probed by TMA-DPH or DPH were observed to vary in parallel under nitrendipine therapy. 5. These results suggest that in vivo shear forces participate in the control of erythrocyte membrane fluidity or that erythrocytes adapt their membrane properties to blood flow conditions.

Topics: Antihypertensive Agents; Blood Flow Velocity; Diphenylhexatriene; Erythrocyte Membrane; Female; Fluorescent Dyes; Humans; Hypertension; Male; Membrane Fluidity; Middle Aged; Stress, Mechanical

To verify that platelet cytosolic pH is altered in essential hypertension and to investigate the mechanisms involved.. Cytosolic pH was determined in unstimulated platelets by the fluorescent indicator 2,7-bis-carboxyethyl-5(6)-carboxyfluorescein (BCECF). Membrane microviscosity was evaluated by the fluorescence anisotropies of diphenylhexatriene (DPH) and its cationic derivative trimethylamino-diphenylhexatriene (TMA-DPH).. The cytosolic alkalinization previously observed in platelets from untreated hypertensive patients was confirmed. The buffering capacity appeared unaltered and the cytosolic pH was not modified by 50 mumol/l N-5-ethylisopropylamiloride, a specific inhibitor of the Na(+)-H+ exchange. Exposure to external Na(+)-free media produced an intracellular acidification that was similar in hypertensive and normotensive donors and maintained the cytosolic pH difference between the two groups. In the two blood pressure groups platelet cytosolic pH varied inversely with the steady-state anisotropy of TMA-DPH but not with that of DPH. Experimentally induced acidification of the cytosol by Na+ removal with or without nigericin treatment was accompanied by rises in TMA-DPH anisotropy.. This study of platelet intracellular pH in essential hypertension confirms cytosolic alkalinization and demonstrates its association with changes in the dynamic properties of the platelet plasma membrane.

Topics: Blood Platelets; Cell Membrane; Cytosol; Diphenylhexatriene; Female; Fluoresceins; Fluorescence Polarization; Humans; Hydrogen-Ion Concentration; Hypertension; Male; Membrane Fluidity; Middle Aged

1. The metabolism of blood platelets, taken as an accessible model of excitable cells, has been reported to be altered in hypertension. Most of the identified alterations concern the functions of various plasma membrane constituents. 2. A possible modification of membrane microviscosity was investigated by 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene fluorescence depolarization. In order to determine whether or not the membrane structures probed by these indicators were related to platelet physiological functions, the cytosolic free Ca2+ concentration was determined in parallel. 3. At physiological temperature, the fluorescence anisotropy of 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene was decreased in untreated hypertensive patients (0.276 +/- 0.002 versus 0.288 +/- 0.002, n = 23 and 22, P less than 0.001), indicating a lowered microviscosity at the lipid-water interface of cell membrane. It correlated inversely with blood pressure (P less than 0.001) and cytosolic free Ca2+ concentration (P less than 0.030). On the contrary, 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy was observed to vary with sex but not with blood pressure. 4. These results suggest that structural membrane modifications may participate in the various functional abnormalities observed in platelets from hypertensive patients.

Topics: Blood Platelets; Calcium; Cell Membrane; Diphenylhexatriene; Female; Fluorescence Polarization; Fluorescent Dyes; Humans; Hypertension; Male; Membrane Fluidity; Thrombin; Viscosity

Fluorescence polarization of diphenylhexatriene embedded in membranes was used as an index of 'microviscosity' in platelets and erythrocyte ghosts of spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR), Wistar-Kyoto strain (WKY) and of the hypertension-prone and -resistant Sabra strains (SBH and SBN ), and the original Sabra strain (SB). Microviscosity was increased both in erythrocyte ghosts and platelet membranes of male but not female SHR rats compared with WKY rats and in hypertension-prone Sabra rats compared with the original Sabra rats. Acute and chronic salt loading increased the microviscosity of platelet membranes in all strains of rats but had no effect on the erythrocyte membranes. Microviscosities of vesicles made of lipids extracted from SHR and WKY erythrocyte ghosts were similar. This supports the hypothesis that membrane proteins play a major role in the differences in microviscosity observed in SHR rats.

Topics: Animals; Blood Platelets; Cell Membrane; Cholesterol; Diphenylhexatriene; Erythrocyte Membrane; Female; Fluorescence Polarization; Hypertension; Male; Membrane Fluidity; Membrane Lipids; Membrane Proteins; Rats; Sodium; Viscosity

Topics: Adult; Blood Viscosity; Chemical Phenomena; Chemistry; Diphenylhexatriene; Erythrocyte Indices; Erythrocyte Membrane; Erythrocytes; Female; Humans; Hypertension; Male; Mathematics; Middle Aged

1. The membrane structure of erythrocytes of rats with different forms of arterial hypertension was studied by means of two hydrophobic fluorescent probes (diphenylhexatriene and pyrene). 2. Microviscosity of hydrophobic areas of erythrocyte membrane of spontaneously hypertensive rats was found to be increased compared with that of membranes from normotensive control rats. 3. No alterations of membrane structure of erythrocytes of deoxycorticosterone-treated rats and renal hypertensive rats were found.

Topics: Animals; Desoxycorticosterone; Diphenylhexatriene; Erythrocyte Membrane; Erythrocytes; Female; Fluorescence Polarization; Hypertension; Hypertension, Renal; Male; Pyrenes; Rats; Rats, Inbred Strains