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C Peiró

Publications and source records attributed to C Peiró.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nifedipine, losartan and captopril effects on hyperplasia of vascular smooth muscle from Ren-2 transgenic rats.

Vascular smooth muscle cells from hypertensive transgenic rats for the mouse Ren-2 gene exhibited radioimmunoassayable angiotensin II and hyperplasia in comparison with cells from Sprague-Dawley rats. However, neither captopril, losartan, saralasin, nor PD123319 (all at 10 microM) modified DNA synthesis or cell number observed in 4-day growth curves with 10% fetal calf serum. Nifedipine reduced DNA synthesis in both cell types, the concentration required being significantly higher in Sprague-Dawley- (1 microM) than in transgenic-derived cultures (100 nM). The EC50 values were of 2.43 +/- 0.32 and 1.0 +/- 0.17 microM, respectively (P < 0.05). In both cell types, only 10 microM nifedipine reduced serum-induced cell proliferation, but inhibition percentage was higher in transgenic-derived cultures. In conclusion, hyperplasia of transgenic-derived vascular smooth muscle cells is not blocked by angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, but these cells are more sensitive to the antiproliferative effects of nifedipine.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of captopril, losartan, and nifedipine on cell hypertrophy of cultured vascular smooth muscle from hypertensive Ren-2 transgenic rats.

1. We hypothesized that tissular renin-angotensin system (RAS) induces vascular hypertrophy in hypertensive Ren-2 transgenic rats (TGR; strain name TGR(mRen2)L27). This assumption was tested in cell cultures of vascular smooth muscle (VSMC) from both hypertensive TGR and control normotensive Sprague-Dawley (SD) rats. Planar cell surface area, protein synthesis, and protein content per cell were studied, the role for locally produced angiotensin II (AII) was evaluated and the possible pharmacological interference by different drugs was analysed. 2. By use of radioimmunoassay techniques, AII could be determined in TGR cultures (10.25 +/- 0.12 pg per 10(7) cells) while it could not be detected in SD ones. 3. Under serum-free conditions, VSMC from hypertensive TGR were hypertrophic when compared to SD VSMC, as they presented a higher protein content per cell (335 +/-18 and 288 +/- 7 pg per cell respectively; P<0.05) and increased mean planar cell surface area, as determined by image analysis (4,074 +/- 238 and 4,764 +/- 204 microm2, respectively; P < 0.05). 4. When exogenously added to cultured SD and TGR VSMC, AII (100 pM to 1 microM) promoted protein synthesis and protein content in a concentration-dependent manner without affecting DNA synthesis. Maximal effects were observed at 100 nM. At this concentration, AII effectively increased planar cell surface area in both SD and TGR cultures by approximately 20%. 5. Treatment of TGR cultures, in the absence of exogenous AII, with the angiotensin-converting enzyme inhibitor captopril or the angiotensin AT1 receptors antagonist losartan (100 nM to 10 microM) reduced planar cell surface area in a concentration-dependent manner. In addition, both captopril and losartan (10 microM), decreased protein synthesis by approximately 15%. 6. Treatment of SD VSMC, in the absence of exogenous AII, with both captopril and losartan had no effect either on planar cell surface area or protein synthesis. 7. Treatment with the Ca2+ antagonist nifedipine (100 nM to 10 microM) reduced cell size in both SD and TGR cultures. Maximal cell reduction reached by nifedipine averaged 906 +/- 58 and 1,292 +/- 57 microm2, in SD and TGR, respectively (P<0.05). In addition, nifedipine, nitrendipine and nisoldipine (all at 10 microM) decreased protein synthesis in both cell types by 15-25%. 8. We concluded that cultured VSMC from TGR are hypertrophic in comparison with those from SD. This cell hypertrophy can be the consequence of the expression of the transgene Ren-2 that activates a tissular RAS and locally produces AII, which acts in a paracrine, autocrine, or intracrine manner. Cell hypertrophy in TGR cultures could be selectively reduced by RAS blockade, while nifedipine decreased cell size and protein synthesis in both hypertrophic and non hypertrophic cells.

Angiotensin II↗
PubMed1997

[Cerebral hemorrhage after carotid endarterectomy in a young adult].

INTRODUCTION: Cerebral haemorrhage after carotid endarterectomy is a rare complication. It follows 0.5% to 20% of all endarterectomies, but should be borne in mind because of the morbidity and mortality seen in most cases. CLINICAL CASE: We describe the case of a 42 year old man in whom carotid endarterectomy had been done 7 days before to treat a stenosis of 80%. He complained of a sudden onset of weakness of the right half of his body and changes in his speech. Physical examination showed right inferior facial paresia, right hemiparesia and right extensor cutaneous plantar reflex. On admission to the Emergency Department, before treatment, blood pressure was 80/60. Carotid auscultation and palpation were normal. Cerebral TRC showed a left lenticular haematoma. The patient progressed satisfactorily. DISCUSSION/CONCLUSIONS: We review the literature on the subject as well as the factors which should be considered as possibly predisposing to bleeding after carotid endarterectomy, such as arterial hypertension and occlusion or severe stenosis of the contralateral carotid artery. The detection of patients with the risk of postendarterectomy bleeding by simple noninvasive investigations, such as the transcranial doppler and the acetazolamide test, and early diagnosis of a clinical picture compatible with a hyperperfusion syndrome may contribute to the relief and prevention of sequelae in these patients.

Carotid Stenosis↗
PubMed1996

Effects of indomethacin and iloprost on contraction of the afferent arterioles by endothelin-1 in juxtamedullary nephron preparations from normotensive Wistar-Kyoto and spontaneously hypertensive rats.

The contractile effects of endothelin-1 on the afferent arterioles of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and the modulation of these responses by cyclooxygenase blockade or by the prostacyclin analog iloprost were investigated. For this, the preglomerular vasculature was visualized by using the juxtamedullary nephron preparation. Endothelin-1 (100 pM-1 microM) induced concentration-dependent reduction of afferent diameters either in WKY and SHR kidneys, which were inhibited by 1 microM nifedipine, indicating its dependence on extracellular calcium. After incubation with 20 microM indomethacin, the endothelin-1-induced contractions were potentiated in WKY but abolished in SHR vessels. These results could be explained if endothelin-1 is releasing vasodilator prostanoids in WKY, whereas in SHR preparations, vasoconstrictor prostanoids predominate. The prostacyclin analog iloprost (1 nM-1 microM) did not modify basal diameters of the WKY afferent arterioles, whereas a weak vasodilatatory effect was observed in the SHR afferent vasculature. Both in WKY and SHR preparations, iloprost (10 nM-1 microM) abolished the afferent contractility by endothelin-1, this effect being more prominent in SHR. We conclude that a defective production of vasodilator prostanoids or an enhanced release of vasoconstrictor cyclooxygenase derivatives may determine the renovascular effects of endothelins in SHR kidneys.

Animals↗
PubMed1996

Impairment of endothelium-dependent relaxation by increasing percentages of glycosylated human hemoglobin. Possible mechanisms involved.

High levels of glycosylated human hemoglobin impair nitric oxide-mediated responses. However, the percentage of glycosylation for which this effect is observed and the mechanisms involved are unknown. We tested endothelium-dependent relaxations caused by acetylcholine in rat aortic segments either in control conditions or after preincubation with increasing percentages of glycosylated human hemoglobin. Human hemoglobin (1 and 10 nmol/L) inhibited endothelium-dependent relaxations only when glycosylated at 9% or higher. We evaluated the effect of 14% glycosylated human hemoglobin on acetylcholine-evoked responses in vessels preincubated with scavengers of superoxide anions, hydroxyl radical, or hydrogen peroxide (superoxide dismutase, deferoxamine, and catalase, respectively); with inhibitors of xanthine oxidase, cyclooxygenase, or thromboxane synthase (allopurinol, indomethacin, and dazoxiben, respectively); with blockers of thromboxane A2/prostaglandin H2 or endothelin receptors (SQ 30741 and BQ-123); and with the precursor of nitric oxide synthesis L-arginine. Superoxide dismutase abolished the effect of glycosylated hemoglobin, and the other substances did not have any effect. Glycosylated hemoglobin at 14% did not modify either the vasoconstrictions induced by the blocker of nitric oxide synthase NG-nitro-L-arginine methyl ester or the relaxations evoked in deendothelialized vessels by sodium nitroprusside and 8-bromo-cGMP. However, it inhibited the vasodilations evoked by exogenous nitric oxide. Superoxide dismutase abolished this latter effect. We conclude that the threshold for glycosylated human hemoglobin (Hb A1) to inhibit endothelium-dependent relaxation is 9%. This effect is due to interference with endothelial nitric oxide by means of superoxide anion production.

Acetylcholine↗
PubMed1995

Influence of endothelium on cultured vascular smooth muscle cell proliferation.

The endothelium exerts a large influence on the underlying vascular smooth muscle, not only by the release of both contracting and relaxing factors but also by its ability to synthesize a large number of molecules that influence vascular smooth muscle growth. In addition to well-characterized growth promoters or growth inhibitors, some endothelium-derived factors, originally described as vasoactive compounds, seem to possess growth-regulatory properties. The vasoconstrictor endothelin-1 elicited a dose-dependent increase of cultured vascular smooth muscle cell DNA synthesis with a maximal effect of 57 +/- 14% over basal levels, whereas vasodilators such as prostacyclin, sodium nitroprusside, and 8-bromoguanosine 3':5'-cyclic monophosphate reduced DNA synthesis by 19 +/- 5%, 22 +/- 2%, and 31 +/- 3%, respectively. Medium conditioned by cultured bovine aortic endothelial cells markedly stimulated both DNA synthesis and proliferation of smooth muscle cells. When medium was conditioned in the presence of the endothelin-converting enzyme inhibitor phosphoramidon, the mitogenic effect was significantly reduced, thus indicating a role for endothelin in the stimulation of smooth muscle cell growth by endothelial cells. However, when both cell types were maintained in a coculture system, a 13 +/- 2% decrease of DNA synthesis was observed in smooth muscle cultures. The addition of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester, the cyclooxygenase inhibitor indomethacin, or both during the coculture period did not revert the antiproliferative effect of endothelial cells in coculture, thereby indicating it is not likely due to these unstable endothelium-derived vasorelaxant molecules.

Animals↗
PubMed1995

Endothelial stimulation of sodium pump in cultured vascular smooth muscle.

We studied vascular sodium pump activity and its regulation by vasoactive agents and endothelium in cultured aortic vascular smooth muscle cells from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Baseline sodium pump activity (ouabain-inhibitable 86Rb+ uptake) was similar in cells from both rat strains. Angiotensin II and endothelin-1 increased ouabain-inhibitable 86Rb+ uptake more in SHR than WKY cells, whereas no effects were obtained with sodium nitroprusside, 8-bromo-cGMP, or iloprost. We examined the influence of endothelium on vascular sodium pump activity either by coculturing smooth muscle and endothelial cells or by using conditioned medium. Both coculture for 24 hours with endothelial cells and treatment with conditioned medium increased smooth muscle cell sodium pump activity, this effect being higher in SHR cells. These results suggest that the endothelium may modulate sodium pump activity in the underlying smooth muscle by releasing a diffusible compound, which is more active on SHR smooth muscle. The conditioned medium obtained in the presence of inhibitors of angiotensin-converting enzyme, endothelin-1-converting enzyme, cyclooxygenase, lipoxygenase, and nitric oxide synthase had no effect on the ability of conditioned medium to increase sodium pump activity, suggesting that angiotensin II, endothelin-1, eicosanoids, and nitric oxide are not involved in this stimulatory effect. The nature of the possible endothelial factor involved is still unknown, but it possesses a molecular weight between 25 and 50 kD, is heat stable, and is sensitive to trypsin treatment. We propose it could be a growth factor.

Animals↗
PubMed1994

Functional vascular renin-angiotensin system in hypertensive transgenic rats for the mouse renin gene Ren-2.

1. Isolated aortic segments from transgenic rats for the mouse renin gene Ren-2 were more sensitive than those from control Sprague-Dawley ones to the vasoconstrictions induced by angiotensin II and to the potentiation of norepinephrine contractions by this peptide. 2. In transgenic, but not in control aorta, pretreatment with angiotensinogen potentiated norepinephrine-induced vasoconstrictions, this effect being abolished by captopril. 3. These results suggest that in the aorta of transgenic rats there is a higher functional tissue renin-angiotensin system that potentiates the vascular reactivity to norepinephrine.

Angiotensin II↗
PubMed1993

Phorbol dibutyrate induces contractions in bovine cerebral arteries by an extracellular calcium-independent mechanism.

The aim of the present study was to analyse the ability of phorbol 12,13-dibutyrate (PDB) to activate protein kinase C (PKC), measured by its capacity to translocate the enzyme from the cytosol to the membrane fraction, as well as to induce vasconstrictive responses in segments from branches of bovine cerebral arteries. PDB (0.1 microM) produced a marked translocation of PKC activity from the cytosolic to the membranous fraction. This drug induced concentration-dependent contractions which were slow in onset. The contraction elicited by PDB was reduced by the PKC inhibitor, staurosporine (1 and 10 nM), but unaltered by both Ca(2+)-free medium containing 3 mM EGTA and the Ca(2+)-channel antagonist, nifedipine (1 microM). Preincubation of segments with PDB (10 and 30 nM) reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT) in a concentration- and preincubation time-dependent manner. These data indicate that bovine cerebral arteries possess cytosolic and membranous PKC activities, that the vasoconstrictive responses induced by PDB were independent of extracellular Ca2+, that cytosolic C-kinase is translocated to the membrane and probably down-regulated by PDB, and that this enzyme is not involved in 5-HT responses, but is down-regulated by PDB.

Alkaloids↗
PubMed1992

Comparison of the vasoconstrictor responses induced by endothelin and phorbol 12,13-dibutyrate in bovine cerebral arteries.

The vascular effects of endothelin-1 (ET-1) were compared with those elicited by phorbol 12,13-dibutyrate (PDB), an activator of the protein kinase C (PKC), to analyze the involvement of this enzyme on ET-1 responses. PDB and ET-1 caused slow-developing contractions (sustained and transient, respectively), which were reduced by the PKC inhibitor, staurosporine (1 and 10 nM). Only the contractile effects evoked by ET-1 were reduced in Ca-free medium and by the Ca channel antagonist, nifedipine (1 microM), and increased by the Ca channel agonist, BAY K 8644 (10 nM). PDB (10 and 30 nM) preincubation reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT; 0.01, 0.1 and 1 microM) in a way dependent on phorbol concentration and preincubation time, whereas ET-1 (1 nM) increased the contractile response to 5-HT (0.1 microM). Furthermore, PDB (0.1 microM) also reduced the responses elicited by ET-1 (30 microM) and vice versa. ET-1 (0.1 microM) induced transient translocation of PKC activity from the cytosol to the membrane, which was less than that produced by PDB (0.1 microM). Electrical stimulation induced [3H]noradrenaline (NA) release, which was increased by PDB (10 and 100 nM) and not affected by ET-1 (10 nM). These results indicate: (1) the responses induced by PDB and ET-1 were independent and dependent on extracellular Ca, respectively; (2) PKC is involved in NA release and 5-HT responses, but mainly in desensitization of these responses, and (3) PKC is activated by ET-1 and is implicated in vascular actions of ET-1, but other mechanisms, such as the activation of ET-1 receptors and opening of dihydropyridine-sensitive Ca channels also appear to be involved.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Vascular smooth muscle proliferation in hypertensive transgenic rats.

In vascular smooth muscle cell (VSMC) cultures from Sprague-Dawley (SD) and hypertensive transgenic rats for the mouse renin gene Ren-2 (TGR), the DNA synthesis, which was analyzed by the uptake of [3H]thymidine, was higher in TGR than SD VSMCs (2.5- to 8-fold, mean of 5.6-fold) under basal conditions. DNA synthesis was increased by fetal calf serum (10%) in SD cells more than in TGR VSMCs, and was decreased by heparin (400 micrograms/ml) and by phorbol-12,13-dibutyrate (10(-7) M) in TGR VSMCs to a higher degree than in SD cells. Neither endothelin (10(-7) M), angiotensinogen (10(-8) M), the renin inhibitor CGP 29,287 (10(-4) M), angiotensin I (10(-7) M), captopril (10(-5) M), angiotensin II (10(-7) M), nor saralasin (10(-6) M) modified DNA synthesis in either type of VSMCs. Sodium nitroprusside (10(-4) and 10(-3) M) increased DNA synthesis in both kinds of VSMCs but in TGR cultures it became toxic at 10(-3) M. 8-Bromocyclic GMP (10(-7) to 10(-5) M) reduced DNA synthesis in SD cells more than in TGR VSMCs. These results suggest that (a) cellular mechanisms of proliferation appear to be more activated in TGR VSMCs, likely involving a protein kinase C-dependent pathway but not the renin-angiotensin system, and (b) in both type of cells, sodium nitroprusside possesses proliferative properties whereas 8-bromocyclic GMP has antiproliferative properties.

Animals↗
PubMedDate not supplied

Prevention of endothelial dysfunction in streptozotocin-induced diabetic rats by gliclazide treatment.

The aim of the present work was to analyze whether the oral hypoglycemic drug gliclazide affects diabetic endothelial dysfunction in streptozotocin-induced diabetic rats. Gliclazide was compared with glibenclamide, ascorbic acid, and aminoguanidine. An insulin-dependent model of diabetes was selected to exclude insulin-releasing effects of the drugs. Both in isolated aortic segments and mesenteric microvessels, endothelium-dependent relaxation evoked by acetylcholine (ACh, 1 nM to 10 microM) was significantly reduced in vessels from diabetic animals. This impairment was reversed when the segments were previously incubated with 100 U/ml superoxide dismutase. When streptozotocin-induced diabetic rats were orally treated from the time of diabetes induction with gliclazide (10 mg/kg) or ascorbic acid (250 mg/kg), ACh-induced endothelium-dependent relaxation was well preserved both in aortic segments and mesenteric microvessels. In addition, the impaired vasodilatation to exogenous nitric oxide (NO) in aortic segments was also improved in gliclazide-treated diabetic rats. On the other hand, oral treatment with glibenclamide (1 and 10 mg/kg) or aminoguanidine (250 mg/kg) did not produce significant improvements in diabetic endothelial dysfunction. We conclude that gliclazide reverses the endothelial dysfunction associated with diabetes. This effect appears to be due not to the metabolic actions of the drug but rather to its antioxidant properties, as it can be mimicked by other antioxidants. We propose that the mechanism involved is the inactivation of reactive oxygen species, which are increased in diabetes probably as a result of increased early protein glycosylation products, such as glycosylated hemoglobin (HbA(1c)). These effects of gliclazide are not shared by other oral hypoglycemic agent such as glibenclamide, or by blockade of advanced glycosylation end product (AGE) generation with aminoguanidine.

Acetylcholine↗
PubMedDate not supplied

Correction of glycosylated oxyhemoglobin-induced impairment of endothelium-dependent vasodilatation by gliclazide.

We have investigated whether gliclazide, a second-generation sulfonylurea hypoglycemic agent, interferes with the impairment of endothelium-dependent nitric-oxide-mediated relaxation produced by 14%-glycosylated human oxyhemoglobin (GHHb). For comparative purposes, other agents, like glibenclamide, aminoguanidine, ascorbic acid or superoxide dismutase (SOD), were also tested. GHHb (10 nM) caused a reduction in endothelium-dependent relaxation induced by acetylcholine (1 nM to 10 microM) in both isolated aortic segments and mesenteric microvessels from normoglycemic nondiabetic rats. Preincubation of the vessels with gliclazide (100 nM to 10 microM) prevented the impairment of endothelial relaxation, the threshold concentration of gliclazide being 300 nM. In addition, 10 microM gliclazide also prevented the reduction by 10 nM GHHb of the relaxation induced by exogenous nitric oxide (NO, 10 nM to 100 microM). Determination of superoxide anion release measured by the reduction in ferricytochrome c indicated that GHHb produced significant amounts of these free radicals that were concentration-dependently inhibited by gliclazide. The impairment of endothelium-mediated responses was also prevented by 100 U/ml SOD or 10 microM ascorbic acid, but not by 10 microM glibenclamide or 100 microM aminoguanidine. We conclude that gliclazide can reduce the impairment of nitric-oxide-mediated endothelium-dependent relaxation produced by GHHb. This reduction is likely related to the antioxidant properties of the drug, a mechanism suggested by these studies which demonstrate the inactivation of superoxide anions produced by the glycosylated protein by gliclazide.

Acetylcholine↗
PubMedDate not supplied

[The validity of the classification criteria of the International Headache Society for migraine, episodic tension headache and chronic tension headache].

INTRODUCTION: We analysed the value of the diagnostic criteria of the International Headache Society (IHS) for the classification of the primary headaches in a headache clinic. PATIENTS AND METHODS: The IHS criteria were applied to classify 208 headaches in 194 patients. Forty-two had migraine, 18 tension type headache and 76 chronic daily headaches (CDH). RESULTS: The value of IHS criteria in order to distinguish migraine from tension type headache have a specificity of 94% and a predictive positive value of 99%. The predictive negative value is 63%. The more specific symptoms for migraine were severity, photophobia, phonofobia and vomits. IHS criteria for chronic tension type headache have a very low sensibility; only the 45% of these headaches meet criteria. If we applied the criteria of Silberstein et al we can see that, without the patient history, symptoms don't distinguish between chronic tension type headache, transformed migraine and new daily persistent headache. The most specific features for distinguishing the transformed migraine were worsening with activity, vomiting and pulsating. A 62% of the CDH have analgesic overuse. CONCLUSIONS: IHS criteria distinguish accurately between migraine and tension type headache. Symptoms do not differenciate the different kinds of CDH.

Chronic Disease↗
PubMedDate not supplied

[Vascular hemichorea: clinical-radiological correlation].

INTRODUCTION: Hemichorea is uncommon in acute cerebrovascular accidents. Its appearance is in relation to the contralateral involvement of the basal ganglia, particularly the striate ganglion. With current neuroimaging techniques it is possible to identify the lesions responsible for these abnormal movements. Magnetic resonance (MR) is the technique of choice for detection of small sized lesions. OBJECTIVE: We have analysed our series of patients to try to relate the site of the lesion to the appearance of chorea. PATIENTS AND METHODS: We made a retrospective study of the cases of hemichorea of vascular origin admitted between January 1993 and April 1999. In all cases, cerebral CAT and/or MR had been done to find the site of the lesion. RESULTS: A total of 10 patients with an average age of 72.5 years (range: 55-85) was found. In eight of them (80%) lesions were found in the basal ganglia, half of which were of ischemic type and the other half hemorrhagic. The sites were: caudate nucleus in one case (10%), thalamus in two cases (20%) and capsulo-lenticular lesions in five cases (50%). All lesions were contralateral to the side of the body affected except in one case with a left thalamic haematoma and homolateral hemichorea. CONCLUSIONS: The lesions found were very varied in site. In 20% of the cases they were not detected by conventional neuroimaging techniques. This fact supports the concept of a functional global network of the basal ganglia which may be interrupted at several points and lead to the same clinical findings.

Aged↗
PubMedDate not supplied

[Cesarean section on a full-term parturient with convulsive crises].

A 34-years-old woman in her 35th week of pregnancy experienced epileptic seizures and underwent emergency cesarean delivery of a healthy boy under general anesthesia. The patient had no history of epilepsy and the seizures were later attributed to an intracerebral cavernous angioma. She received treatment with phenytoin and was asymptomatic 3 months later. Although seizures unrelated to preeclampsia or eclampsia in pregnancy are rare, differential diagnosis must determine the etiology of the crisis.

Adult↗