Biomedical subjects

P Marche

Publications and source records attributed to P Marche.

At least 37 records · Page 2Linked to original sources

PubMed1994

Effect of erythropoietin on DNA synthesis, proto-oncogene expression and phospholipase C activity in rat vascular smooth muscle cells.

The administration of recombinant human erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. The experiments of the present study were designed to explore the hypothesis that rHuEpo might exert mitogenic effects on vascular smooth muscle cells (VSMCs), and that pre-existing hypertension might be a predisposing condition. Cultured aortic VSMCs from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both rat strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and inositol phosphate formation, respectively. Exposure of VSMCs to rHuEpo for various periods gradually increased the levels of c-myc and JunB mRNAs and transiently induced c-fos mRNA expression as determined by Northern analysis. The hormone-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and a modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.

Animals↗

PubMed1994

Signaling mechanisms of basic fibroblast growth factor in arterial cells from genetically hypertensive rat.

The mechanisms of vascular structural alterations in hypertension were studied in cultured adventitial fibroblasts isolated from aortas of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Basic fibroblast growth factor (bFGF)-, epidermal growth factor (EGF)-, or platelet-derived growth factor (PDGF)-induced DNA synthesis and phospholipase C activity were estimated by determining 3H-thymidine incorporation and 3H-inositol phosphate production, respectively. The role of protein tyrosine kinases was assessed by stimulating the cells in the presence of tyrphostin, a protein tyrosine kinase inhibitor. Both the mitogenic potency of bFGF, EGF, and PDGF and the phospholipase C activity elicited by these factors were increased markedly in SHR (v WKY) fibroblasts. SHR fibroblasts were significantly less sensitive to tyrphostin inhibition of bFGF-induced 3H-thymidine incorporation than WKY fibroblasts, whereas when the cells were stimulated with EGF, PDGF, or 5% serum, SHR and WKY fibroblasts were equally sensitive to tyrphostin inhibition. At doses that abolished bFGF-induced 3H-thymidine incorporation, tyrphostin did not affect bFGF-induced 3H-inositol phosphate production. These results indicate that in aortic fibroblasts phospholipase C activation is not sufficient for bFGF-induced DNA synthesis. They suggest that tyrosine kinase activation is a necessary step in the transduction of bFGF mitogenic signal and plays an important role in the enhanced DNA synthesis exhibited by SHR (v WKY) cells. Therefore, one may envisage that bFGF contributes, through paracrine/autocrine mechanisms, to the vascular smooth muscle hyperplasia/hypertrophy in SHR.

Animals↗

PubMed1994

Involvement of calcium channels in fibroblast growth factor-induced activation of arterial cells in spontaneously hypertensive rats.

To gain insight into the mechanisms that could account for the abnormal vascular structure in spontaneously hypertensive rats (SHR) and to determine whether this could be affected by calcium channel blockers, we compared the influence of dihydropyridines on basic fibroblast growth factor (bFGF)-induced DNA synthesis in cultured adventitial fibroblasts isolated from SHR and Wistar-Kyoto rat (WKY) aorta. Our results showed that (a) bFGF was a potent mitogen for adventitial fibroblasts, much more active in SHR-derived than in WKY-derived cells, thus confirming the hyperreactivity of the SHR arterial cells; (b) the mitogenic potency of bFGF could be reduced by dihydropyridines (rank order of potency was nifedipine approximately nisoldipine > nitrendipine > nimodipine); and (c) the nifedipine inhibitory effect could be completely and partially antagonized in WKY- and SHR-derived fibroblasts, respectively, by the calcium channel agonist Bay K 8644. Moreover, the extent of nifedipine inhibitory extent increased and decreased in SHR- and WKY-derived fibroblasts, respectively, according to duration of treatment of cells with the drug, suggesting that SHR fibroblasts became progressively more sensitive whereas those of WKY became more refractory to the drug treatment. These data indicate that in aortic fibroblasts stimulated by bFGF, L-type calcium channels participate in the antimitotic effect of dihydropyridines and suggest the existence of interactions between these channels and the bFGF signaling pathways. They also suggest that nifedipine inhibits bFGF-induced DNA synthesis by different mechanisms in SHR and WKY fibroblasts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

[Mitogenic effect of erythropoietin on cultured aortic myocytes].

The administration of recombinant erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. In the present study, experiments were designed to explore the hypothesis that rHuEpo could enhance vascular resistance through mitogenic effect on vascular smooth muscle cells (VSMCs), and that preexisting hypertension might be a predisposing condition. Cultured VSMCs from the thoracic aortae of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and 3H-inositol phosphate formation, respectively (EC50 approximately 4 U/ml). Exposure of VSMCs to rHuEpo for various times gradually increased the levels of c-myc and junB and transiently induced c-fos expression, as determined by Northern analysis. rHuEpo-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.

Animals↗

PubMed1993

Mitogenic events induced by vasopressin in aortic fibroblasts from spontaneously hypertensive rats.

1. To further explore the mechanisms of arterial growth, we investigated the signalling pathways through which arginine-vasopressin acts as a mitogen in cultured adventitial aortic fibroblasts of the spontaneously hypertensive rat, and we examined the mechanisms involved in the hyperresponsiveness to arginine-vasopressin of fibroblasts from spontaneously hypertensive rats compared with fibroblasts from Wistar-Kyoto rats. 2. Arginine-vasopressin-induced [3H]thymidine incorporation was used to determine the peptide mitogenicity. Arginine-vasopressin-triggered hydrolysis of phosphoinositides by phospholipase C was evaluated by measuring [3H]inositol phosphate formation. The role of protein kinase C and protein tyrosine kinases in arginine-vasopressin mitogenicity was assessed by stimulating the cells with arginine-vasopressin in the presence of 12-O-tetradecanoylphorbol 13-acetate and tyrphostin (a tyrosine kinase inhibitor), respectively. 3. Arginine-vasopressin-induced DNA synthesis was completely abolished in confluent cells, whereas [3H]inositol phosphate formation was only reduced. The presence of 12-O-tetradecanoylphorbol 13-acetate markedly decreased arginine-vasopressin-induced [3H]thymidine incorporation in fibroblasts from spontaneously hypertensive rats and was without effect in fibroblasts from Wistar-Kyoto rats. Tyrphostin abolished arginine-vasopressin-induced [3H]thymidine incorporation in a dose-dependent manner and did not affect the formation of inositol phosphates. 4. These results indicate that phospholipase C activation is not sufficient for arginine-vasopressin-induced mitogenesis. They also suggest that (i) tyrosine kinase activation is a necessary step in the transduction of the arginine-vasopressin mitogenic signal, and (ii) protein kinase C participates in the increased mitogenic potency of arginine-vasopressin in spontaneously hypertensive rats.

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PubMed1992

Protein kinase C and cell proliferation in spontaneously hypertensive rats.

Cultured aortic fibroblasts from spontaneously hypertensive rats (SHR) exhibit increased proliferation rate compared with cells from normotensive Wistar Kyoto (WKY) rats. The present study was designed to investigate whether this growth abnormality could be accounted for by alteration in protein kinase C (PKC). The enzyme activation by 12-O-tetradecanoyl phorbol 13-acetate (TPA) promoted 3H-thymidine incorporation which was higher in SHR-derived fibroblasts compared with WKY-derived cells. Likewise, 3H-phorbol 12,13-dibutyrate (PDBu) binding to intact cells was markedly increased in SHR-derived fibroblasts. These findings suggest a difference in PKC activity between the two cell types. In both cell types, serum-induced 3H-thymidine incorporation was enhanced by PKC down-regulation, which was obtained by prolonged treatment of cells with high dose of TPA, whereas it was inhibited in a dose-dependent manner by activation of the enzyme. The changes in serum-induced 3H-thymidine incorporation elicited either by activation or desensitization of PKC, did not differ between SHR and WKY fibroblasts. Our results indicate therefore i) that in the presence of serum PKC exerts an antiproliferative effect in rat aortic fibroblasts and ii) that the increase in PKC activity and in sensitivity to TPA exhibited by SHR-derived fibroblasts, is not involved in the increased proliferation rate displayed by SHR-derived fibroblasts in serum-containing medium.

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PubMed1991

Increased proliferation of adventitial fibroblasts from spontaneously hypertensive rat aorta.

By using aortic adventitial fibroblasts in culture as a model, we first demonstrated that cells derived from spontaneously hypertensive rats (SHR), when compared with Wistar-Kyoto (WKY)-derived cells, possessed an increased capacity to proliferate and to synthesize DNA in response to vasoactive agents. At this early stage of culture, SHR fibroblasts exhibited a higher specific growth rate. Then, to gain insight into the mechanisms which could be responsible for the difference observed, signalling pathways involved in the transduction of the mitogenic signal were analysed in cells cultured for 3 days. Results indicated that, in SHR-derived fibroblasts, an increased phospholipase C activity could account for the higher mitogenic response to thrombin or vasopressin. However, this enzymatic activity, which did not differ when fibroblasts from the two rat strains were stimulated by serum, could not be responsible for the enhanced proliferation rate of SHR-derived cells. Moreover, neither protein kinase C nor pertussis toxin-sensitive G proteins appeared to contribute to the hyperresponsiveness exhibited by SHR fibroblasts. Our results indicate that the mechanism(s) responsible for such a difference vary according to the stimulus; they also suggest that adventitial fibroblasts may participate in the modified reactivity of vascular wall associated with hypertension.

Animals↗

PubMed1991

[Study of mechanisms responsible for hyperproliferation of aortic cells in spontaneously hypertensive rats].

In order to determine the mechanisms which could be responsible for the hypertrophy of vascular wall associated with primary hypertension, we have investigated the mechanisms involved in the proliferation of aortic cells from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. In this study we have examined the role of phospholipase C which is responsible for the formation of second messengers, the function of protein kinase C and that of GTP-binding proteins (G proteins) which couple membrane receptors to phospholipase C. The adventitial fibroblasts from thoracic aorta were chosen as cell model in culture. The capacity of proliferation in response to 10% serum was analyzed by cell number determination and by measuring the incorporation of 3H-thymidine into newly synthesized DNA. Our results showed that SHR-derived fibroblasts proliferated more rapidly and incorporated more 3H-thymidine than WKY-derived fibroblasts. However, the phospholipase C activity, measured by the serum-stimulated production of 3H-inositol phosphates in cells prelabeled with 3H-inositol, did not differ between SHR- and WKY-derived cells. The desensitization of protein kinase C, by long term (2 d) treatment with high dose (300 nM) of phorbol 12-myristate, 13-acetate (TPA), markedly augmented, but to the same extent, the 3H-thymidine incorporation into DNA of SHR- and WKY-derived fibroblasts. Moreover, protein kinase C activation by TPA caused a parallel reduction (25-30%) of the incorporation of 3H-thymidine into DNA of SHR- and WKY-derived cells. Under the same experimental conditions, the growth of SHR- and WKY-derived fibroblasts was reduced by TPA in a dose-dependent manner (up to 20%) to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[Activation mechanisms by thrombin and vasopressin of fibroblasts in spontaneously hypertensive rats].

To gain insight into the mechanisms that could account for the augmentation of cellular reactivity in primary hypertension, we have examined some of the biochemical events which are implicated in the transmission of mitogenic signal as well as in cell reactivity. This study focussed on phospholipase C, protein kinase C and GTP-binding proteins (G-proteins), in response to thrombin or arginin-vasopressin (AVP). Cultured fibroblasts prepared from the adventitia of thoracic aorta of spontaneously hypertensive rat (SHR) were used as cell models and were compared with fibroblasts prepared from controls Wistar-Kyoto (WKY) rats. The mitogenicity of each agonist was estimated by measuring the incorporation of 3H-thymidine into the newly synthesized DNA. The agonist-induced phospholipase C activity was evaluated by measuring the production of 3H-inositol phosphates in cells prelabeled with 3H-inositol. The influence of protein kinase C and that of G proteins on the mitogenesis in cells stimulated by thrombin or AVP was determined by pretreating cells with phorbol 12-myristate, 13-acetate (TPA) and pertussis toxin, respectively. Kinetics and dose response studies have demonstrated that in response to thrombin and AVP, the phospholipase C activity and the incorporation of 3H-thymidine were significantly higher in the fibroblasts derived from SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

Receptor-dependent and -independent protein phosphorylation in platelets of spontaneously hypertensive rats.

This study investigates the role of protein kinase C and of myosin light chain kinase in mediating platelet hyperresponsiveness in spontaneously hypertensive rats (SHR). For this purpose, 32P-labeled washed platelets of both SHR and normotensive controls Wistar-Kyoto (WKY) were challenged either with a receptor-mediated agonist (thrombin) or with direct activators of myosin light chain kinase and protein kinase C. Such enzymatic activities were assessed by measuring changes in 32P-labeling of their respective target proteins, namely myosin light chain (20 KDa) and the 47 KDa protein. In resting platelets, the patterns of protein phosphorylation were similar between SHR and WKY, suggesting that the two cell types were in a comparable quiescent status. By contrast, in both dose-response and time-course studies, thrombin promoted a significantly greater phosphorylation of the 20- and 47 KDa proteins in platelets of SHR compared with that for WKY. Sensitivity of myosin light chain kinase to the calcium ionophore A23187 and of protein kinase C to both phorbol ester and dioctanoylglycerol was apparently not different between the two cell types. The data indicate that the exaggerated thrombin-induced protein phosphorylation observed for platelets of SHR is not linked to alterations in protein kinase C and/or myosin light chain kinase per se. These results therefore suggest that platelet hyperresponsiveness in SHR is likely to be related, at least in part, to abnormalities in receptor-mediated transmembrane signalling.

Animals↗

PubMed1990

Protein kinase C and platelet reactivity in spontaneously hypertensive rats.

Since protein kinase C (PKC) plays an important role in the control of platelet biological responses, we investigated whether it can be involved in the enhanced platelet reactivity to thrombin which is observed in spontaneously hypertensive rats (SHR) in comparison to that observed in controls (WKY). PKC activity was determined by measuring the phosphorylation of P47 protein (the endogenous substrate of PKC in the platelet). Mean effective concentration (EC50) values for phorbol ester and synthetic diacylglycerol (direct activators of PKC) were similar in SHR and WKY, thus revealing similar intrinsic activity of PKC in both rat strains. EC50 values for thrombin were approximately 30% lower in SHR v WKY. Enhanced PKC activity in SHR is likely the result of an increased diacylglycerol formation and release of Ca2+ from intracellular pools, consequent to an increased thrombin-induced phospholipase C activity.

Animals↗

PubMed1990

Platelet phospholipase C activity in salt-dependent hypertension.

In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with 32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05-0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Platelet phosphatidylcholine turnover in experimental hypertension.

To gain insight into the membrane alteration that could account for the hyperresponsiveness of platelets in hypertension, we have investigated whether, in resting platelets of hypertensive rats, the metabolism of phospholipids was modified. Because preliminary results indicated a specific acceleration of phosphatidylcholine turnover in spontaneously hypertensive rats, the possible relation between such an abnormality and hypertension was investigated by studying phosphorus-32 labeling of phosphatidylcholine (taken as an index of its turnover) in various experimental models of hypertension. The data showed that phosphatidylcholine turnover 1) was considerably increased in platelets from spontaneously hypertensive (even at the prehypertensive stage) and stroke-prone rats compared with Wistar or Wistar-Kyoto control rats, 2) did not differ between deoxycorticosterone-salt-treated hypertensive and control rats, and 3) was increased in Dahl salt-sensitive rats fed a high NaCl diet (hence hypertensive rats), compared with either the rats fed a low NaCl diet or the salt-resistant rats. These results indicate that an increase in phosphatidylcholine turnover is a consequence of neither hypertension nor high salt intake and appears likely to be of genetic origin. These data allow us to suggest the existence, in platelets, of a relation between phosphatidylcholine turnover, free cytoplasmic Ca2+, and responsiveness to stimuli. Because phosphatidylcholine is assumed to participate in signal transduction, an increase in its turnover in platelets might be considered as a primary membrane abnormality that, in primary hypertension, results in platelet hyperresponsiveness.

Animals↗

PubMed1990

[Membrane abnormalities and cellular hyperreactivity in different models of hypertension].

In various models of hypertension of genetic origin, a hypersensitivity of phospholipase C has been demonstrated to participate in the hyperreactivity of platelets toward a variety of vasoactive agents. Since this abnormality could not be observed in the absence of cell stimulation, it could not account for the increase in free Ca2+ which has been reported in resting platelets in primary hypertension. Likewise, in hypertensive subjects, platelets behave hyperactive when stimulated by ADP, although the stimulus has been demonstrated to be a poor activator of phospholipase C. In order to gain insight into the membrane alteration that could account for the cellular hyperactivity which characterizes hypertensive subjects, we investigated, in resting platelets, the kinetics of radioactive labeling of major membrane phospholipids. Isolated platelets were prepared from SHR (4w and 17w of age), SHR-SP, Dahl salt-resistant and salt-sensitive rats fed either a low or a high salt diet, DOCA-salt hypertensive rats and from the appropriate normotensive controls. Irrespective of the radioactive precursor used (32P-orthophosphate, 3H-glycerol, 3H-choline), the labeling of phosphatidylcholine (PC) was markedly (up to 20 fold) enhanced in SHR (whichever their age) and SHR-SP compared with WKY. This increase, specific of PC, could not be accounted for by differences either in the actual amount of PC or in the uptake of various labels, suggesting an increased PC turnover. Such an increase was also observed in platelets of Dahl hypertensive rats but not in those of DOCA-salt hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

[Increased phosphorylations of proteins involved in the expression of the physiologic response of platelets in SHR rats].

In primary hypertension, phospholipase C (PLC) is hypersensitive in several target tissues (platelets, vascular smooth muscle cells, aortic fibroblasts). Protein kinase C (PKC) and myosin light chain kinase (MLCK), which are physiologically activated by PLC-triggered second messengers (diacylglycerol and Ca2+ ions, respectively), phosphorylate specific proteins closely involved in the cell functional responses. In this study, we have examined and compared between platelets of spontaneously hypertensive rats (SHR) and their normotensive controls Wistar-Kyoto (WKY), the patterns of protein phosphorylation obtained either with the receptor-mediated agonist thrombin (i.e. which acts via PLC) or with direct activators of the protein kinases, PKC and MLCK. Activation by thrombin of 32P-prelabeled platelets induced incorporation of radioactivity into two proteins, P20 (myosin light chain) and P47. The curves obtained when platelets were challenged with either increasing doses of thrombin (0.025-0.3 U/ml) for 20 sec or with a low dose of the agent (0.1 U/ml) for up to 1 min, revealed that phosphorylation of the target proteins of PKC (P47) and of MLCK (P20) were significantly enhanced in platelets of SHR compared to WKY. In contrast, direct activation of PKC by phorbol ester and of MLCK by the calcium ionophore A23187 evoked the selective phosphorylation of the respective target proteins, P47 and P20, to a similar extent in platelets of SHR and WKY. Taken together, these results demonstrate that a physiological agonist (thrombin) induces an enhanced phosphorylation of intracellular proteins in platelets of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Enhanced proliferating activity of cultured smooth muscle cells from SHR.

In order to explore the cellular mechanisms responsible for the vascular abnormalities observed in hypertension, smooth muscle cells (SMC) were cultured after enzymatic digestion of aortas from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). These cultures were performed in the presence of fetal calf serum (FCS) and stimulated by vasoactive agents (angiotension II, serotonin, bradykinin). Growth rate was determined by cell counting and measurement of nuclear-tritiated thymidine incorporation and phospholipase C (PLC) activation by measurement of 3h-inositol mono-, di-, tri-, and tetra-phosphates formed from preincorporated 3h-myo-inositol. Cells from SHR proliferate more actively than control ones in the presence of 10% FCS but don't significantly differ at lower concentrations. In the presence of 5% FCS angiotensin II (10(-7) mol/L), 5-HT (10(-6) mol/L) and bradykinin (10(-6) mol/L) enhance cell proliferation and their effect is more important in cultures from SHR. The phospholipase C activation induced by these drugs was also more important in these SHR cultures than in control ones. The PLC hyperreactivity observed in SHR cells may therefore be involved in their enhanced proliferating activity evidenced in culture and in the vascular abnormalities described in vivo.

Animals↗

PubMed1989

Salt-induced and spontaneous hyperactivity of phospholipase C in primary hypertension.

Previous studies from our laboratory have shown that platelets from both spontaneously hypertensive rats and essential hypertensive patients exhibited an increased thrombin-triggered phospholipase C activity compared with normotensive subjects. In order to determine the relationship between phospholipase C and hypertension we investigated this enzymatic activity in Dahl salt-resistant (Dahl R/Jr) and salt-sensitive (Dahl S/Jr) rats fed either a low- or a high-NaCl diet, and in DOCA-NaCl hypertensive rats. Phospholipase C activity was increased in the Dahl S/Jr rats fed a high-NaCl diet compared to a low-NaCl diet. This difference was not observed in the Dahl R/Jr rats, irrespective of diet. Likewise, phospholipase C activity was similar in the DOCA-NaCl hypertensive rats compared with their controls. Our results indicate that the increased platelet phospholipase C activity was not a consequence of either the blood pressure elevation or the high NaCl intake and was probably of genetic origin. While the increased phospholipase C activity was not correlated with blood pressure, the enhanced enzymatic activity in Dahl S/Jr hypertensive rats may be involved in the elevation of blood pressure and may be NaCl-regulated.

Animals↗

PubMed1989

[Phospholipase C hypersensitivity in hypertensive rats results from innate and acquired factors].

In spontaneously hypertensive rats (SHR), enhanced activity of phospholipase C (PLase C) has been reported in various cells and tissues. In particular, the increased PLase C activity of platelets has been described as being involved in the hyperactivity to thrombin exhibited by these cells in SHR and in some patients with essential hypertension. In order to determine the relationship between such an enzymic abnormality and hypertension, the PLase C activity of platelets was investigated in various models of experimental hypertension, i.e. Dahl rats and DOCA-salt hypertensive rats. PLase C activity was determined by measuring the thrombin-induced 32P-phosphatidic acid (32P-PA) formation from 32P-prelabeled platelets. In parallel, experiments on the platelet reactivity was assessed by measuring the thrombin-induced serotonin secretion from 3H-serotonin prelabeled platelets. In Dahl salt-resistant rats (DR), the blood pressures were 123 +/- 6 and 118 +/- 7 mmHg for animals fed a low (0.3 p. 100) and high (4 p. 100) salt diet, respectively; the blood pressures of Dahl salt-sensitive rats (DS) were 159 +/- 6 and 202 +/- 11 mmHg, respectively. Hypertensive rats of the DOCA/salt--treated group exhibited a blood pressure of 210 +/- 8 mmHg compared with 137 +/- 4 mmHg for those of the control group. At rest (ie before stimulation) the platelets of all groups of animals behave similarly with respect to the incorporation of 32P and its metabolism into phospholipids as well as the uptake of serotonin. These data indicate therefore that platelets were in a similar quiescent status.(ABSTRACT TRUNCATED AT 250 WORDS)

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