Biomedical subjects

J Sassard

Publications and source records attributed to J Sassard.

At least 37 records · Page 2Linked to original sources

PubMed1997

Polymorphisms in the carboxy-terminus of the epithelial sodium channel in rat models for hypertension.

OBJECTIVE: To investigate whether mutations in the C-terminus of the three subunits of the rat epithelial sodium channel (alphabetagamma-rENaC) contribute to the hypertensive phenotype in five rat models for essential hypertension. DESIGN: We sequenced the C-terminal regions of alpha-, beta- and gamma-rENaC genes in five different hypertensive rat strains [spontaneously hypertensive rats (SHR), Dahl salt-sensitive (SS/Jr) rats, Milan hypertensive (MHS) rats, Sabra hypertensive (SBH) rats and Lyon hypertensive rats (LHR)] and their normotensive controls [Wistar-Kyoto (WKY) rats, Dahl salt-resistant (SR/Jr) rats, Milan normotensive (MNS) rats, Sabra normotensive (SBN) rats and Lyon normotensive rats (LNR)]. Identified polymorphisms were tested for cosegregation with blood pressure as well as for increased epithelial sodium channel (ENaC) activity. METHODS: Genomic DNA extracted from hypertensive and normotensive rat strains was amplified by the polymerase chain reaction and polymerase chain reaction fragments were sequenced. Cosegregation analysis was performed to test for correlations between blood pressure and different genotypes. The effects of a polymorphism on ENaC activity were assessed by functional expression in Xenopus laevis oocytes. The chromosomal location of the gene for gamma-ENaC was determined by linkage analysis in an F2 (MHS x MNS) population. RESULTS: We found no polymorphisms at the C-terminus of alpha- and beta-rENaC in the five rat models tested. We identified two polymorphisms at the C-terminus of the gamma-subunit, one leading to an amino acid change. Milan strains (MNS and MHS) were polymorphic for this mutation. By cosegregation analysis we could exclude the possibility that there was a correlation between blood pressure and this polymorphism. Functional expression of the polymorphism caused no increase in ENaC activity assessed by measurement of the amiloride-sensitive sodium current in Xenopus oocytes. The gene for the gamma-ENAC was located on rat chromosome 1. CONCLUSIONS: No polymorphisms at the C-terminus of the three subunits of the epithelial sodium channel cosegregating with blood pressure were detected in five different genetic rat models for hypertension. If an altered ENaC activity contributes to the pathogenesis of hypertension in these rats, it must thus arise from mutations in other parts of the protein, from mutations outside the coding region impairing the proper regulation of one of the subunits or from mutations in an ENaC-associated protein.

Animals↗

PubMed1997

Analysis of phenotypic consequences of renin gene polymorphism in Lyon rats.

OBJECTIVE: To investigate phenotypic consequences of renin gene polymorphism between Lyon hypertensive (LH) and normotensive (LN) rats because previously we demonstrated cosegregation of the LH allele with increased blood pressure in a cross of LH with LN rats. DESIGN: Two studies were conducted. Study 1 used a cohort of male F2 rats from a LH x LN cross. Eighty-two rats homozygous for the hypertensive (HH) renin gene allele were compared with 82 rats homozygous for the normotensive (NN) allele. Urinary steroid excretion was measured in 24 h urine samples collected from rats aged 6 weeks. The direct aortic blood pressure was recorded in 30-week-old rats and, after they had been killed, their kidney renin concentration (KRC) was measured. In study 2, renin, angiotensinogen and angiotensin converting enzyme plasma concentrations and renin messenger RNA (mRNA) levels were measured in renal and extra-renal tissues from 6- and 25-week-old LH and LN parental and HH and NN F2 male rats. METHODS: Urinary steroids and plasma components of the renin-angiotensin system (RAS) were measured using specific radioimmunoassays. mRNA levels were quantified by northern blotting. RESULTS: In study 1, HH F2 rats had a higher blood pressure (151.5 +/- 8.2 versus 146.0 +/- 7.4 mmHg, P < 0.001) and a lower KRC (514 +/- 203 versus 666 +/- 304 micrograms A1/h per g cortex, P < 0.01) than did NN rats aged 30 weeks. In covariate analysis the decrease in KRC in HH rats was attributable to their increased blood pressure rather than to the renin genotype. The renin genotype of rats aged 6 weeks was not associated with a change in the urinary excretion of aldosterone, desoxycorticosterone, corticosterone or 18-hydroxy desoxycorticosterone. In study 2, we found no difference either in plasma levels of RAS components or in renal or extrarenal renin mRNA levels either between parental LH and LN rats or between HH and NN F2 rats apart from a higher plasma renin concentration in LH rats aged 6 weeks. Renal, but not extra-renal, renin mRNA levels declined with age. CONCLUSIONS: We found no evidence of a renin genotype-dependent phenotypic difference in the RAS that could account for the effect of the renin locus on blood pressure in Lyon rats. Our findings suggest that the effect of the locus on blood pressure might be due to an as yet unidentified gene linked to renin.

Animals↗

PubMed1997

Lack of insulin resistance in the Lyon hypertensive rat.

Genetically hypertensive rats (LH) of the Lyon strain, compared to their normo-tensive (LN) controls associate, in a unique manner, high blood pressure with increases in body weight and in plasma lipids and insulin/glucose ratio. The present work investigated the development of insulin resistance with age in this model. At the age of 22 and 52 weeks, LH and LN fasted male rats were submitted to an intravenous glucose tolerance test, allowing measurement of the elimination rate of the glucose and the area under the curve of the insulin response. Insulin sensitivity was calculated as the ratio of these two parameters. It was observed that insulin sensitivity coefficient decreased with age in all the animals and that LH rats did not significantly differ from LN controls (from 62.6 +/- 3.3 and 69.1 +/- 4 at 22 weeks to 42.1 +/- 4.4 and 49.5 +/- 12.8 at 52 weeks for LH and LN rats, respectively). It is concluded that 1) elevated plasma insulin/glucose ratio does not mean insulin resistance and 2) hypertension can develop without being associated, even in aged rats, to a true insulin resistance.

Age Factors↗

PubMed1997

Pivotal role of the renin-angiotensin system in Lyon hypertensive rats.

We assessed the role of the renin-angiotensin system (RAS) in Lyon genetically hypertensive (LH) and normotensive (LN) rats by measuring 1) kidney renin and prorenin contents; 2) effects of early, prolonged angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and regional hemodynamics; and 3) acute and chronic responses to angiotensin II (ANG II) and norepinephrine (NE). At the adult age, LH rats differed from LN rats by elevated BP, left ventricle weight, and vascular resistances, especially in the kidneys, associated with lower kidney renin and prorenin contents. ACE inhibition (perindopril, 3 mg.kg-1.24 h-1 orally from 3 to 15 wk of age) suppressed the development of hypertension, cardiac hypertrophy, and the increase in renal vascular resistances. No specific hypersensitivity to ANG II could be disclosed in acute conditions. In perindopril-treated LH rats, a 4-wk infusion of ANG II (200 ng.kg-1.min-1) but not of NE (1,000 ng.kg-1.min-1) restored hypertension, mimicked the hemodynamic alterations seen in untreated LH rats, and produced a brief sodium retention. It is concluded that in LH rats, despite a low basal renin secretion, hypertension and hemodynamic abnormalities 1) are fully dependent on an active RAS and 2) may involve an enhanced sensitivity to the chronic effects of ANG II.

Aging↗

PubMed1996

Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.

The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.

Animals↗

PubMed1996

Left ventricular weight but not blood pressure is associated with sex chromosomes in Lyon rats.

OBJECTIVE: To investigate, by studying reciprocal back-crosses to Lyon hypertensive (LH) rats, the involvement of sex chromosome loci in high blood pressure and heart weight in LH rats. METHODS: Reciprocal F1 and F'1 generation male rats obtained from male LH x female Lyon normotensive (LN) and male LN x female LH crosses respectively, male back-cross rats obtained from male LH x female F1 or F'1 and from male F1 or F'1 x female LH crosses, and parental LH and LN male rats were studied at 29-31 weeks of age. Systolic, diastolic, mean and pulse pressures were measured beat to beat in unrestrained rats for 1 h. In addition, relative left and right ventricular weights were measured. RESULTS: The average blood pressures did not differ between F1 and F'1 rats or between the four populations of back-cross rats. On the contrary, the relative left ventricular weight was higher in F'1 than in F1 rats. As a role for loci on the Y chromosome could be discarded by comparison of the two populations of back-cross rats, which differ only in the origin of their Y chromosome, this increase in the relative left ventricular weight of F'1 rats was consistent with an effect of a locus on the LH X chromosome. This was supported by findings in the back-cross populations, those populations in which 100% of the rats carried an LH X chromosome having a significantly higher left ventricular weight than those in which only 50% of the rats carried such a chromosome. The estimate of the genetic determination was higher for left ventricular weight (41%) than for mean arterial pressure (19%). Although these two parameters were associated in the back-cross population, the origin of the X chromosome had no influence on this association. CONCLUSIONS: These findings indicate that, against the genetic background provided by the cross studied and at the age studied, the sex chromosomes of LH and LN rats do not contain loci at which alleles differentially influence blood pressure. They do, however, suggest that relative left ventricular weight in this model has a specific genetic determination, partly contributed by a locus on the X chromosome.

Animals↗

PubMed1996

Comparison between chronic converting enzyme inhibition and AT1 blockade in mRen2 transgenic rats.

We compared the consequences of chronic angiotensin-converting enzyme (ACE) inhibition with quinapril and of specific AT1 blockade with losartan in a renin-dependent model of hypertension, the (mRen2)27 transgenic rats (TG). Animals were orally treated with 10 mg/kg/24 h of either quinapril (TGQ, n = 13) or losartan (TGL, n = 12) from age 4 to age 9 weeks. Indirect systolic blood pressure (SBP), and sodium and water balances were measured for 3 consecutive weeks. Nine-week-old rats were instrumented to record aortic BP in the conscious state. In addition, they received an infusion of glucose and saline to increase their diuresis and thus allow accurate assessment of their renal excretion during short time periods. These rats were studied for three one-h periods: (a) baseline, (b) after the administration of a bradykinin (BK) antagonist, and (c) after a cross-treatment; i.e., TGQ rats receiving losartan (10 mg/kg intravenously, i.v.) and TGL rats receiving quinapril (10 mg/kg i.v.). TGL rats differed from TGQ rats by an unconsistently lower indirect SBP associated with significantly lower urinary volume and sodium excretion, whereas the sodium balance did not differ between the two groups. In conditions of fixed sodium intake the aortic BP of TGQ rats was still nonsignificantly different from that of TGL rats, and TGQ rats also exhibited two-fold higher natriuresis. The BK antagonist had no effect in either group, whereas losartan decreased the BP of TGQ rats. We conclude that in TG rats ACE inhibition is associated with an increased natriuresis as compared with specific AT1 blockade, an effect that is independent of the sodium intake. Because a BK antagonist had no effect, such a difference might be due to an antinatriuretic effect of AT2 receptors in chronic conditions.

Angiotensin II↗

PubMed1996

Elevated epidermal growth factor receptor levels in hypertensive Lyon rat kidney and aorta.

1. The adult spontaneously hypertensive Lyon rats (LH strain) exhibited increased maximal epidermal growth factor (EGF) binding in freshly prepared kidney and aortic tissue membranes compared with age-matched normotensive (LN) or hypotensive (LL) strains. However, the binding affinity of the receptors to EGF was the same in all the three strains studied. These findings indicate an increased number of EGF receptors (EGFR) in the hypertensive LH strain. 2. Protein tyrosine kinase activity associated with the EGFR was also elevated in the LH strain compared with LN or LL strains, indicating that these receptors are functionally active. 3. There was a correlation between maximal EGF binding by aortic membranes and blood pressure in individual animals (r = 0.55; P < 0.001). 4. Taken together with previously reported similar findings in other models of genetic hypertension, the present results suggest a possible role for increased levels of EGFR in the development and maintenance of genetic hypertension.

Analysis of Variance↗

PubMed1996

In the Lyon hypertensive rat, renal function alterations are angiotensin II dependent.

To assess the role of the renin-angiotensin system (RAS) in the renal alterations of the lyon hypertensive (LH) rat, the renal function of LH rats and of their normotensive (LN) controls was studied at different pressure levels after an early and chronic blockade of the RAS by perindopril (3 mg.kg-1.day-1 orally from 3 to 15 wk of age) and after an acute infusion of angiotensin II (ANG II, 10 or 50 ng.kg-1.min-1). Over the range of renal perfusion pressures studied (115-165 mmHg), control LH differed from LN rats by an increased preglomerular vasoconstriction and a blunted pressure-natriuresis curve. Perindopril fully prevented the development of hypertension in LH rats, suppressed their preglomerular vasoconstriction, and markedly improved their pressure-natriuresis. In perindopril-treated LH, ANG II produced a greater reduction in renal blood flow, glomerular filtration rate, and urinary sodium excretion that was not significantly modified by blockade of thromboxane A2-prostaglandin H2 receptors. These results indicate that the blood pressure level and the renal function of LH rats are closely dependent on an active RAS.

Angiotensin II↗

PubMed1996

Analysis of quantitative trait loci for blood pressure on rat chromosomes 2 and 13. Age-related differences in effect.

Previous studies have suggested the presence of quantitative trait loci (QTLs) influencing blood pressure on rat chromosomes 2 and 13. In this study, we mapped the QTLs in F2 rats derived from a cross of the spontaneously hypertensive rat and the Wistar-Kyoto rat and analyzed the effect of the QTLs on blood pressures measured longitudinally between 12 and 25 weeks of age. We analyzed 16 polymorphic markers spanning 147.3 cM on chromosome 2 and 13 markers spanning 91.6 cM on chromosome 13. Both chromosomes contained QTLs with highly significant effects on blood pressure (peak logarithm of the odds [LOD] scores, 5.64 and 5.75, respectively). On chromosome 2, the peak was localized to a position at anonymous marker D2Wox7, 2.9 cM away from the gene for the sodium-potassium ATPase alpha 1-subunit. On chromosome 13, the major peak coincided with the marker D13Mit2, 21.7 cM away from the renin gene, but there was a suggestion of multiple peaks. The effect of the QTL on chromosome 2 was seen throughout from 12 to 25 weeks of age, whereas interestingly, the effect for the QTL on chromosome 13 was maximal at 20 weeks of age but disappeared at 25 weeks of age, presumably because of the effect of either epistatic factors or environmental influences. The findings provide important information on QTLs influencing blood pressure on rat chromosomes 2 and 13 that will be useful in localizing and identifying the causative genes and emphasize the importance of age being taken into account when the effects of individual QTLs on a trait that shows significant age-related changes are being analyzed.

Aging↗

PubMed1996

Major cardiovascular risk factors in Lyon hypertensive rats. A correlation analysis in a segregating population.

OBJECTIVE: To investigate the association of blood pressure with the other major cardiovascular risk factors in a large population of back-cross to Lyon hypertensive (LH) rats. METHODS: Mean arterial pressure was recorded in male freely moving Lyon normotensive (LN), LH, F1 and backcross to LH rats aged 30 weeks. Plasma cholesterol, triglycerides, insulin, creatinine, urea, fibrinogen and haematocrit levels, and the insulin: glucose ratio were measured in 31-week-old rats and 24h albuminuria in 6-week-old rats. RESULTS: Adult LH rats exhibited a significant increase in plasma lipids, insulin, fibrinogen, creatinine, urea and haematocrit levels compared with LN rats. In young LH rats, at an age at which blood pressure is slightly increased, albuminuria was increased to a greater extent than expected from their blood pressure levels. In the adult back-cross to LH rats, only the plasma cholesterol level was associated with blood pressure. Moreover, the plasma cholesterol level was related to fibrinogen and haematocrit levels. Finally, in the same rats, albuminuria developed early in life was positively related to hypercholinesterolaemia measured later in life. CONCLUSION: Plasma cholesterol, fibrinogen, haematocrit levels and early albuminuria could act synergistically in the enhancement or the development, or both, of vascular and kidney damage in the LH rat. Most interestingly, the association between plasma cholesterol level and blood pressure indicates that, as in essential hypertension, hypercholesterolaemia is a major phenotype associated with hypertension in the LH rat.

Albuminuria↗

PubMed1995

Alterations of cytosolic calcium in platelets and erythrocytes of Lyon hypertensive rats.

Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pHi) (including their responses to thrombin), as well as erythrocyte [Ca2+]i and 45Ca2+ influx, were studied in Lyon hypertensive (LH) and normotensive (LN) rats aged 3 months. Platelets of LH rats were characterized by substantially elevated basal [Ca2+]i values, higher [Ca2+]i levels after thrombin stimulation, and enhanced initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Basal platelet pHi values were not significantly different in LH and LN animals but thrombin elicited a significant alkalinization only in LH platelets. Erythrocytes of LH rats had an enhanced initial rate of 45Ca2+ and tended to elevated [Ca2+]i levels. Our data indicate profound alterations in cell Ca2+ handling in platelets and erythrocytes of LH rats, similar to those previously described in spontaneously hypertensive rats of the Okamoto-Aoki strain. The analysis of the relations between blood pressure, plasma lipids, and cell Ca2+ handling suggested that triglycerides, but not cholesterol, might be involved in altered platelet Ca2+ handling in LH rats.

Animals↗

PubMed1995

Pharmacokinetics of piroximone after oral and intravenous administration to patients with renal insufficiency.

The pharmacokinetics of piroximone (PI) were determined in patients with renal failure (inulin clearance less than 50 ml min-1 per 1.73 m2) using two protocols: (a) 10 patients received a single i.v. infusion of 0.5 mg kg-1 PI and the data were compared with those from seven healthy subjects receiving the same regimen; (b), a single oral dose of either 25 or 50 mg PI was given to 20 patients. PI concentrations were assayed by h.p.l.c. in plasma and urine over 48 h. After i.v. administration to healthy subjects PI was distributed rapidly and eliminated with a mean half-life of 1.3 +/- 0.2 h. The urinary recovery of unchanged PI was 64% of the dose. In the patients the extent of renal elimination of PI was decreased (-78%) in relation to the degree of renal insufficiency as assessed by inulin clearance (r = 0.97, P < 0.0001). Mean Cmax, AUC and t1/2,z values after i.v. infusion were increased by 47%, 127% and 77%, respectively, in comparison with healthy subjects. Similar results were obtained after oral administration. Until chronic dosing studies are undertaken, PI dosage should be adapted in relation to renal function.

Administration, Oral↗

PubMed1995

Subtype 2 of angiotensin II receptors controls pressure-natriuresis in rats.

Angiotensin II recognizes two receptor subtypes, AT1 and AT2, both of them having been recently cloned. Although AT2 receptors represent 5-10% of angiotensin II receptors in the kidneys of adult rats, their function remains unknown. In the present work, we examined the possible contribution of AT2 receptors to the regulation of pressure-natriuresis in anesthetized rats infused either with the specific AT2 antagonist PD 123319, or with CGP 42112B, an AT2 ligand with agonistic properties. The effects of PD 123319 were examined in a preparation with stable levels of angiotensin II, and in which AT1 receptors were blocked by the specific antagonist losartan. The effects of CGP 42112B were studied in rats deprived of endogenous angiotensin II. AT2 receptor blockade with PD 123319 did not change the renal blood flow while it increased the diuresis and natriuresis. These effects persisted even after full AT1 receptor blockade with losarfan. CGP 42112B did not modify the renal blood flow, but dose-dependently decreased urine flow and natriuresis. These results show that, contrary to AT1 receptors, renal AT2 receptors have no effect on total renal blood flow, but blunt the pressure-natriuresis, thus demonstrating that this receptor subtype is involved in a function of importance for body fluid and blood pressure regulation.

Angiotensin I↗

PubMed1995

Prostaglandins and sodium handling in Lyon hypertensive rats.

1. In the Lyon model, genetically hypertensive (LH) rats can be compared to both normotensive (LN) and low-blood pressure (LL) control rats. 2. Using either in vitro or in vivo approaches it was observed that LH kidneys differed from LN and LL controls by a preglomerular vasoconstriction and a decreased slope of the pressure-natriuresis curve. 3. Since young LH rats exhibited an increased urinary excretion of thromboxane (Tx) B2, the stable derivative of TxA2, the role of vasoconstrictor metabolites of arachidonic acid was investigated. Using isolated kidneys, it was demonstrated that LH kidneys did not synthesize a higher amount of TxA2 than LN or LL controls in baseline conditions but after stimulation by vasoconstrictor agents. 4. This finding suggests that such an increased ability to synthesize TxA2 may amplify the normal effect of other vasoconstrictors and thus participate in the increased renal vascular resistance observed in LH rats. 5. That hypothesis was confirmed since the blockade of the TP receptors, on which both prostaglandin H2 and TxA2 act, suppressed the preglomerular vasoconstriction seen in LH kidneys. However TP receptor blockade was devoid of effect on the pressure-natriuresis abnormalities.

Animals↗

PubMed1995

Silica attenuates hypertension in Lyon hypertensive rats.

BACKGROUND AND OBJECTIVE: Evidence has been provided suggesting an association between hypertension and immune dysfunction in Lyon hypertensive (LH) rats. In the present study, we investigated the possible role played by macrophages in LH rats by examining the blood pressure consequences of the chronic administration of silica, a selective toxin to macrophages in vivo. DESIGN AND METHODS: LH and Lyon low blood pressure (LL) male rats were treated with silica at a dose of 200 mg/kg per week intraperitoneally from age 4-10 weeks. Controls received saline. Blood pressure was measured by plethysmography from age 6-10 weeks and an intra-arterial recording was performed in 11-week-old, freely moving rats. RESULTS: Treatment with silica did not modify blood pressure in LL rats at any age. In contrast, 1 week after the beginning of the treatment, the blood pressure of silica-treated LH rats was lower than that of untreated LH rats. As shown by intra-arterial recording, the effect persisted 1 week after cessation of the treatment. In addition, silica decreased the left ventricle weight in LH but not in LL rats. CONCLUSION: The present results show that weekly administration of silica in young LH rats attenuates the development of hypertension and of left ventricular hypertrophy, a finding which suggests that macrophage-mediated immune reactions may play a pathogenic role in LH rats.

Animals↗

PubMed1995

Partial transfer of genetic hypertension by lymphoid cells in Lyon rats.

BACKGROUND AND OBJECTIVE: The involvement of immune factors in a given disease is suggested by evidence that a disease can be prevented by immunosuppression and can be transferred by lymphoid cells. Because the first type of experimental result was achieved in Lyon hypertensive (LH) rats, the present study was undertaken to determine whether hypertension can be transferred to normotensive recipients. As a control, the blood pressure effects of lymphoid cell grafts from renovascular hypertensive donors were also determined. DESIGN AND METHODS: Splenocytes and lymph node cells from LH and Lyon low-blood pressure (LL) rats with two-kidney Goldblatt hypertension were respectively injected into LH x Lyon normotensive (LN) F1 hybrids and LL rats aged 7, 8, 9 and 10 weeks. Blood pressure was measured by plethysmography from age 6 to 13 weeks and an intra-arterial recording was performed in 14-week-old conscious rats. RESULTS: Lymphoid cell injections from LL rat donors with two-kidney hypertension did not modify the blood pressure of LL rat recipients. In contrast, lymphoid cell grafts from LH rat donors induced a significant increase in blood pressure in F1 recipients compared with control F1 rats after the first injection. As confirmed by intra-arterial recording, this blood pressure effect lasted until age 14 weeks (145 +/- 1 versus 137 +/- 1 mmHg in grafted and ungrafted F1, respectively). It was not related to alterations in the acute role of the renin-angiotensin and sympathetic nervous systems and was not associated with increased pressor responses to the vasoconstrictor drugs tested. CONCLUSION: The present study demonstrates that genetic hypertension can be partially transferred by lymphoid cells in F1 recipients. The effect seems to be specific to genetic hypertension because lymphoid cells from renovascular hypertensive donors failed to transfer this secondary form of hypertension. The present results support the hypothesis that cellular immune reactions contribute to the pathogenesis of hypertension and LH rats.

Animals↗

PubMed1994

Platelet and erythrocyte membrane microviscosity in Lyon hypertensive rats.

The altered membrane microviscosity demonstrated in various cells of spontaneously hypertensive rats (SHR) and essential hypertensive (EH) patients has been proposed to play an important role in the pathogenesis of genetic forms of hypertension. The aim of this study was to evaluate possible changes of membrane microviscosity in platelets and red cell ghosts of Lyon hypertensive (LH) and normotensive (LN) rats. Both erythrocyte and platelet membranes of LH rats had a clear tendency to reduced DPH fluorescence anisotropy reflecting the decreased core membrane microviscosity. On the other hand, there were no changes in TMA-DPH fluorescence anisotropy that characterizes the dynamic properties of the outer membrane leaflet. DPH, but not TMA-DPH, anisotropy correlated negatively with blood pressure. This was true for both red cell ghosts and platelets. Membrane microviscosity had no significant relationship to plasma cholesterol or triglycerides. In platelets, TMA-DPH anisotropy correlated positively with cytosolic free calcium concentration ([Ca2+]i). A similar trend was observed in erythrocytes. In contrast, DPH anisotropy had an inverse relationship to platelet [Ca2+]i. It can be concluded that the alterations of membrane microviscosity seen in LH rats are completely different from those reported in SHR animals and that surface and core membrane microviscosity differ in their relationship to blood pressure and [Ca2+]i.

Animals↗