Biomedical subjects

P Lacolley

Publications and source records attributed to P Lacolley.

At least 19 recordsLinked to original sources

PubMed2006

5-HT activates vagal afferent cell bodies in vivo: role of 5-HT2 and 5-HT3 receptors.

Occipital artery (OA) injections of 5-HT elicit pronounced reductions in heart rate and mean arterial blood pressure (MAP) in urethane-anesthetized rats by activation of vagal afferent cell bodies in the ipsilateral nodose ganglion. In contrast, internal carotid artery (ICA) and i.v. injections elicit similar cardiovascular responses by activation of peripheral vagal afferent terminals. The aim of this study was to examine the roles of 5-HT3 and 5-HT2 receptors in the 5-HT-induced activation of vagal afferent cell bodies and peripheral afferent terminals in urethane-anesthetized rats. OA, ICA and i.v. injections of 5-HT elicited dose-dependent reductions in heart rate and MAP that were virtually abolished after i.v. administration of the 5-HT3 receptor antagonists, MDL 7222 or ICS 205-930. The responses elicited by the OA injections of 5-HT were markedly diminished after i.v. injection of the 5-HT2 receptor antagonists, xylamidine or ketanserin, whereas the responses elicited by i.v. or ICA injections of 5-HT were not affected. The present findings suggest that (1) 5-HT3 and 5-HT2 receptor antagonists gain ready access to nodose ganglion cells upon i.v. administration, and (2) functional 5-HT3 and 5-HT2 receptors exist on the cell bodies of vagal afferent neurons mediating the cardiovascular responses elicited by OA injections of 5-HT. These findings also support a wealth of evidence that 5-HT3 receptors exist on the peripheral terminals of vagal afferents, and although they do not discount the possibility that 5-HT2 receptors exist on peripheral vagal afferent terminals, it appears that activation of these receptors does not have pronounced effects on 5-HT3 receptor activity on terminals that mediate the hemodynamic responses to 5-HT.

Analysis of Variance↗

PubMed2006

Occipital artery injections of 5-HT may directly activate the cell bodies of vagal and glossopharyngeal afferent cell bodies in the rat.

The primary objective of this study was to determine whether circulating factors gain direct access to and affect the activity of vagal afferent cell bodies in the nodose ganglia and glossopharyngeal afferents cell bodies in the petrosal ganglia, of the rat. We found that the occipital and internal carotid arteries provided the sole blood supply to the nodose ganglia, and that i.v. injections of the tracer, Basic Blue 9, elicited strong cytoplasmic staining in vagal and glossopharyngeal afferent cell bodies that was prevented by prior ligation of the occipital but not the internal carotid arteries. We also found that occipital artery injections of 5-HT elicited pronounced dose-dependent reductions in heart rate and diastolic arterial blood pressure that were (1) virtually abolished after application of the local anesthetic, procaine, to the ipsilateral nodose and petrosal ganglia, (2) markedly attenuated after transection of the ipsilateral vagus between the nodose ganglion and brain and virtually abolished after subsequent transection of the ipsilateral glossopharyngeal nerve between the petrosal ganglion and the brain, (3) augmented after ipsilateral transection of the aortic depressor and carotid sinus nerves, and (4) augmented after transection of all ipsilateral glossopharyngeal and vagal afferent nerves except for vagal cardiopulmonary afferents. These findings suggest that blood-borne 5-HT in the occipital artery gains direct access to and activates the cell bodies of vagal cardiopulmonary afferents of the rat and glossopharyngeal afferents of undetermined modalities.

Analysis of Variance↗

PubMed2003

Effect of chronic heart rate reduction with ivabradine on carotid and aortic structure and function in normotensive and hypertensive rats.

BACKGROUND: A reduction of heart rate (HR) by surgical means or pharmacological agents affects the progression and/or regression of atherosclerotic lesions. Nevertheless, the effect of bradycardia per se on large artery structure and function has never been investigated in rat models of hypertension. METHODS: Four groups of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were treated for 28 days either by placebo or by the selective HR-reducing agent ivabradine (8.4 mg/kg/day), a novel compound devoid of inotropic or vasodilating effects and without direct action on the autonomic nervous system. At the end of the follow-up period, intra-arterial blood pressure, carotid pulsatile arterial hemodynamics (echo tracking techniques) and the medial cross-sectional area (MCSA) of the aorta and the carotid artery were determined. RESULTS: In conscious animals, chronic administration of ivabradine significantly reduced HR by 26-30% with no change in tail systolic blood pressure. In anesthetized animals, the decrease in HR and the subsequent increase in the diastolic period were responsible for a decrease in diastolic blood pressure. At the site of the large arteries, ivabradine produced a decrease in the MCSA of the thoracic but not of the abdominal aorta, as well as an increase in pulsatile change of the carotid diameter without change in the isobaric distensibility and MCSA. The changes in pulsatile diameter were significantly larger in WKY rats than in SHRs. CONCLUSION: In normotensive and mainly in SHRs, selective chronic HR reduction by ivabradine is associated with alterations in large arteries involving an aortic antihypertrophic effect.

Animals↗

PubMed2001

Mechanical properties and structure of carotid arteries in mice lacking desmin.

OBJECTIVE: Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS: To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves of the common carotid artery (CCA) in homozygous (Des -/-), heterozygous (Des +/-) and wild-type (Des +/+) mice. To evaluate the mechanical strength, we have measured the in vitro intraluminal pressure producing the rupture of the carotid artery wall. The structure analysis of the arterial wall was based on histology and electronic microscopy. RESULTS: A lower distensibility and an increase of arterial wall viscosity were observed in Des -/- compared with Des +/+. Arterial thickness of Des -/- was similar to those of Des +/+, without changes in elastin and collagen contents. Electron microscopy revealed that the perimeter of cellular fingerlike-projections was smaller in Des -/-, indicating that the cells have lost part of their connections to the extracellular matrix. The rupture pressure was significantly lower in Des -/- (1500+/-200 mmHg) compared with Des +/+ (2100+/-80 mmHg) indicating a lower mechanical strength of the vascular wall. No significant difference was found between Des +/- and Des +/+. CONCLUSION: The desmin is essential to maintain proper viscoelastic properties, structure and mechanical strength of the vascular wall.

Analysis of Variance↗

PubMed2001

Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats.

OBJECTIVES: Because the synthesis of aldosterone is mainly modulated by angiotensin II through type I receptor stimulation and because converting enzyme inhibition (CEI) does not modify aortic extracellular matrix in old normotensive rats, the aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in old Sprague-Dawley normotensive rats. BACKGROUND: We have previously shown that long-term aldosterone antagonism prevents the age-related increase in aortic collagen accumulation in young spontaneously hypertensive rats, independent of blood pressure changes. In contrast, we reported that the positive effects of CEI in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type I receptors. METHODS: For this purpose, we studied the histomorphometric and stiffness (echo-tracking technique) changes of an eight-week treatment with the aldosterone antagonist spironolactone by comparison with placebo. RESULTS: At the end of treatment, spironolactone in conscious animals did not change intra-arterial blood pressure, aortic and carotid wall thickness, and cardiac weight. Cardiac collagen density and, to a lesser extent, carotid collagen and elastin densities and contents were significantly decreased in association with an increase of carotid distensibility. CONCLUSIONS: These results show that in old normotensive rats, spironolactone can markedly prevent cardiac and, to a lesser extent, arterial fibrosis and improve arterial stiffness, despite a lack of hypotensive effect.

Age Factors↗

PubMed2001

Angiotensin II type 1 receptor-153A/G and 1166A/C gene polymorphisms and increase in aortic stiffness with age in hypertensive subjects.

OBJECTIVES: Arterial stiffness is associated with excess morbidity and mortality, independently of other cardiovascular risk factors. Age is the main determinant responsible for arterial wall changes leading to arterial stiffening. Environmental and genetic factors may however influence the magnitude of the effects of age on large artery stiffness. DESIGN AND METHODS: The present study assessed whether or not the relationship between age and aortic stiffness was influenced by genetic variants of angiotensinogen (AGT 174T/M, 235M/T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 receptor (AT1 1166A/C, -153A/G) and aldosterone synthase (CYP11B2 -344T/C). This study was realized in 441 untreated hypertensive subjects of European origin (aged 18-74 years). Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). RESULTS: Carriers of the angiotensin II type 1 receptor -153G allele showed a steeper age/PWV relationship than the AT1 -153AA subjects. The effect of the AT1 -153A/G polymorphism on aortic stiffness became apparent after the age of 55 years. In subjects with the AT1 1166C allele, the relationship age/PWV is shifted upward, indicating higher values of aortic stiffness at any age compared to the AT1 1166AA patients. Carriers of both the AT1 1166C and -153G alleles presented the additive effects of these 2 genotypes on aortic stiffness. Angiotensinogen, ACE and CYP11B2 genotypes did not influence the effects of age on PWV. CONCLUSIONS: AT1 receptor genotypes could influence arterial ageing in hypertensive subjects. These results also show that the association between genotypes and arterial stiffness may manifest itself later in life.

Adolescent↗

PubMed2001

Fenestrations of the carotid internal elastic lamina and structural adaptation in stroke-prone spontaneously hypertensive rats.

Our aim was to determine the structural factors that determine the mechanical adaptation of the carotid arterial wall in stroke-prone hypertensive rats (SHRSP). Distensibility-pressure and elastic modulus-stress curves assessed by in vivo echo-tracking measurements indicated a reduction in arterial stiffness in 13-week-old SHRSP compared with Wistar-Kyoto rats (WKY). Elastin and collagen contents determined biochemically were not different between SHRSP and WKY. Confocal microscopy showed that the mean area of fenestrations and fraction of area occupied by fenestrations of the internal elastic lamina (IEL) were smaller in SHRSP than in WKY, which indicated a reduction in stress-concentration effects within the IEL. Immunohistologic staining of EIIIA fibronectin isoform and total fibronectin (also as determined by Western blot) was greater in SHRSP, which suggested increased cell-matrix interactions. We suggest that these structural modifications of the vascular wall play a synergistic role in the mechanical adaptation to a high level of stress in SHRSP.

Animals↗

PubMed2001

Effects of valsartan on mechanical properties of the carotid artery in spontaneously hypertensive rats under high-salt diet.

The aim of this investigation was to evaluate the influence of a high-salt diet (HSD) on the effects of valsartan, an angiotensin II type 1 (AT(1)) receptor antagonist, on carotid arterial stiffness and structure in spontaneous hypertensive rats (SHR). Carotid arterial stiffness was studied in SHR receiving a HSD or a normal-salt diet (NSD) from the 10th to 20th week of age. Within each of the 2 groups, the animals received treatment with either placebo or valsartan (30 mg. kg(-1). d(-1)) administered on the 4th to 20th week of age. Arterial pressure, wall stress, incremental elastic modulus (Einc), medial cross-sectional area, and EIIIA fibronectin isoform were significantly increased in placebo-HSD rats compared with placebo-NSD rats with no change in the ratio of collagen to elastin. Valsartan reduced mean arterial pressure in both NSD and HSD rats but reduced pulse pressure only in NSD rats. In NSD rats, valsartan reduced Einc and medial cross-sectional area. In HSD, valsartan increased Einc and did not modify medial cross-sectional area and fibronectin. In valsartan-treated rats, the ratio of collagen to elastin was greater in HSD than in NSD rats. In conclusion, the effects of AT(1) blockade are greatly influenced by salt intake in SHR. Despite a reduction in mean arterial pressure in HSD rats, AT(1) blockade was not able to prevent the effects of a HSD on pulse pressure, carotid artery stiffness, and hypertrophy.

Animals↗

PubMed2001

Mechanical strength of the isolated carotid artery in SHR.

We have previously reported an adaptation of arterial wall elasticity in spontaneously hypertensive rats (SHR) that involves an increase in both fibronectin/alpha5beta1-integrin complexes and smooth-muscle elastic lamellae connections. We examined the mechanical strength (MS) of the carotid artery in relation to its elastic properties, its elastin/collagen content, and the structure of the internal elastic lamina. MS was defined as the in vitro intraluminal pressure and wall stress that produces rupture of the vascular wall. Intact carotid arteries from 3-month-old normotensive rats (Wistar-Kyoto, WKY) and SHR were cannulated on a specially designed device and adjusted to their in situ length. A slowly increasing static pressure was applied until wall rupture occurred to determine the static mechanical behavior and MS. Static elasticity was similar in SHR and WKY, as were the rupture pressure (2740+/-90 versus 2740+/-40 mm Hg) and wall stress at rupture (11.5+/-1.0 versus 12.8+/-0.4 MPa), indicating equivalent MS in both groups. Histological examination showed several wall ruptures and dissociation of lamellar units that did not differ significantly between the 2 groups. Confocal microscopy showed that the size of fenestrations of the internal elastic lamina and the fraction of area occupied by them were reduced 3-fold in SHR. We have demonstrated that static elasticity of the arterial wall and mechanical strength are similar in carotid arteries from SHR and WKY.

Animals↗

PubMed2000

Intrinsic stiffness of the carotid arterial wall material in essential hypertensives.

We have previously shown that the decrease in large artery distensibility observed in patients with essential hypertension (HT group) was primarily due to an increase in distending pressure and not to hypertension-associated structural modifications of the artery, suggesting a functional adaptation of the wall material. To evaluate the elastic properties of the wall material of the common carotid artery, we determined Young's incremental elastic modulus (Einc) in the HT group and in normotensive subjects (NT group) as a function of blood pressure and circumferential wall stress. In 102 HT patients with never-treated essential hypertension and 40 age- and gender-matched NT subjects, the Einc-pressure and Einc-stress curves were calculated from intima-media thickness and from diameter and pressure waveforms, determined with echo tracking and aplanation tonometry, respectively. The "effective" stiffness of the wall material, determined through Einc calculated at mean blood pressure, was significantly higher in the HT than in the NT group. The "intrinsic" stiffness of the wall material, determined through Einc calculated at a common circumferential wall stress, did not differ between the 2 groups. However, when each group (HT and NT) was analyzed according to tertiles of age, the "intrinsic" stiffness of the arterial wall material was increased only in younger HT patients. In middle-aged and older HT patients, the intrinsic mechanical properties of the carotid arterial wall material were unchanged, and the increased stiffness of the common carotid artery in the HT group was due primarily to the increased level of blood pressure. These results also indicate that the deleterious effects of aging and hypertension on "intrinsic" stiffness are not additive.

Adult↗

PubMed2000

Freeze-drying allows double nonradioactive ISH and antigenic labeling.

Because tissue freeze-drying is an excellent way to preserve antigenic conformation, we have tested the feasibility of this technique to reveal nonradioactive in situ hybridization (ISH) of tissue mRNA. We have compared mRNA detection after different methods of tissue preservation, freeze-drying, cryosectioning, and formaldehyde or methanol fixation. Our results show that nonradioactive ISH is more sensitive for tissues preserved by freeze-drying than for other tissue preparations. We have demonstrated that freeze-drying allows combination of ISH and immunohistochemistry for simultaneous detection of mRNA and antigen because with this technique of tissue preservation ISH does not affect the sensitivity or the amount of the detected antigens. This work underscores the fact that tissue freeze-drying is an easy, convenient, and reliable technique for both ISH and immunohistochemistry and achieves excellent structural conditions for nonradioactive detection.

Animals↗

PubMed1999

Association between local pulse pressure, mean blood pressure, and large-artery remodeling.

BACKGROUND: The aim of the present study was to determine the respective influences of local pulse pressure and mean blood pressure on arterial remodeling in humans at 2 arterial sites: a central, predominantly elastic artery (the common carotid artery) and a peripheral muscular artery (the radial artery). METHODS AND RESULTS: Forty-three healthy subjects and 124 never-treated hypertensive patients were included in the study. Intima-media thickness and internal diameter of the carotid and radial arteries were noninvasively determined with high-definition echo-tracking devices. Pulse pressure was measured locally with applanation tonometry. Multivariate regression models including mean blood pressure and local pulse pressure were established in the whole population. Carotid internal diameter and intima-media thickness were strongly influenced (P<0.0001) by carotid pulse pressure but not by mean blood pressure or brachial pulse pressure, independently of age and sex. Radial artery internal diameter was correlated with age but not with mean blood pressure or radial pulse pressure. Radial artery intima-media thickness was correlated with mean blood pressure (P<0.001) but not with radial pulse pressure. CONCLUSIONS: Carotid pulse pressure was a strong independent determinant of carotid artery enlargement and wall thickening, whereas mean blood pressure and brachial pulse pressure were not, indicating the prominent influence of local pulsatile mechanical load on arterial remodeling. These relationships were observed at the site of an elastic artery but not at the site of a muscular artery, suggesting the contribution of cyclic stretching to the pulse pressure-induced arterial remodeling.

Adult↗

PubMed1999

Central pulse pressure is a major determinant of ascending aorta dilation in Marfan syndrome.

BACKGROUND: In patients with Marfan syndrome (MFS), brachial pulse pressure (PP) has been recognized as a risk factor for aortic dilatation, leading to aortic dissection, the main cause of premature death. However, the relationships between aortic PP, aortic stiffness, and aortic root dilation have not been investigated. Our main objective was to determine whether central PP, which takes into account wave reflections and aortic stiffness, is a better determinant of ascending aorta diameter than brachial PP in MFS patients. METHODS AND RESULTS: Twenty patients with confirmed MFS and 20 age- and sex-matched control subjects were included in this cross-sectional, noninvasive study. Elastic properties of the abdominal aorta and common carotid, common femoral, and radial arteries were calculated from the pulsatile changes in arterial diameter and pressure. The ascending aorta diameter, measured with conventional echocardiography, was 37% larger in MFS than in control subjects (P<0.001). Arterial distensibility was 38% lower in MFS than in control subjects at the site of the abdominal aorta (P<0.01) but not at other sites (common carotid, common femoral, and radial arteries). Independently of age and body surface area, ascending aorta diameter was positively correlated with carotid PP in MFS (P<0. 01) and negatively in control subjects (P<0.01) but was not correlated with brachial PP and mean blood pressure. CONCLUSIONS: In patients with MFS, local PP, estimated from carotid PP, was a major determinant of ascending aorta diameter, whereas brachial PP was not. Increased arterial stiffness was confined to the aorta.

Adult↗

PubMed1999

Arterial structural changes with verapamil in spontaneously hypertensive rats.

Reducing pulse pressure might be more powerful than reducing mean arterial pressure to obtain regression of vascular hypertrophy. However, this hypothesis has never been investigated in the conduit arteries of intact hypertensive animals. A group of 4-week-old spontaneously hypertensive rats (SHR) was treated with the calcium-entry blocker verapamil (50 mg/kg) for 16 weeks and compared with untreated SHR and control Wistar Kyoto (WKY) normotensive rats of the same age. At the end of the experiment, intraarterial thoracic aorta blood pressure was measured both in the conscious and anesthetized animals. Carotid artery diameter and stiffness (echo-tracking techniques) and aortic histomorphometry were determined in parallel. With verapamil, pulse pressure, but not mean arterial pressure, was significantly decreased but did not reach the normotensive values. Carotid internal diameter, medial thickness, and collagen content were significantly reduced by comparison with SHR and did not differ from the values of the WKY group. A significant positive and independent correlation was observed between pulse pressure and medial thickness in the overall population. The study shows that, in SHR chronically treated with verapamil, structural changes may be completely prevented without any change in mean arterial pressure. The parallel change in pulse pressure might suggest that mechanosensitive elements within the vascular wall may be selectively sensitive to the dynamic aspects of physical forces and are able to convert frequency and amplitude information into cellular responses that lead to vascular remodeling.

Animals↗

PubMed1999

[Molecular and cellular determinants of arterial stiffness: role of cell-matrix connections].

Increased large artery stiffness is believed to be a cardiovascular risk factor independent from mean arterial pressure. The mechanical properties of large arteries depend not only on the amounts of their main constituents (elastin, collagen, and smooth muscle cells) but also on the spatial organization and mechanical interactions among these components. These interactions may be mediated by extracellular matrix adhesion proteins and their membrane receptors or integrins. From a mechanical viewpoint, a key element may be the dense plaque, which is composed of cytoskeletal proteins linked to matrix proteins via membrane integrin receptors. Integrin expression in normal and diseased blood vessels is currently the focus of active research. In humans, hypertension-related arterial hypertrophy is not associated with an increase in intrinsic arterial wall stiffness. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHRs). By increasing cell-matrix anchoring, fibronectin may contribute to protect arterial wall components from the increased mechanical loads associated with hypertension. In atherosclerosis, the increase in cell-matrix anchoring plays a key role in preventing atheroma plaque rupture. To determine the exact role of adhesion molecules in arterial stiffness, there is a need for studies involving use of specific anti-integrin agents and of transgenic animal models.

Animals↗

PubMed1998

Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats.

We compared the chronic effects in spontaneously hypertensive rats (SHR) of low doses of an angiotensin converting enzyme inhibitor, trandolapril, a Ca2+ channel antagonist, verapamil, and their combination (trandolapril-verapamil), on arterial mechanical properties, arterial wall hypertrophy and extracellular matrix proteins. Four-week-old SHR were randomly allocated to oral treatment with verapamil (50 mg kg(-1) day(-1)), trandolapril (0.3 mg kg(-1) day(-1)), the combination of verapamil (50 mg kg(-1) day(-1)) plus trandolapril (0.3 mg kg(-1) day(-1)), or placebo for 4 months. A group of Wistar Kyoto (WKY) control rats received placebo for the same period of time. At the end of the treatment, mean blood pressure was lower in verapamil-trandolapril than in trandolapril SHR, but remained higher than in WKY. Verapamil had no effects on blood pressure. Equivalent reduction in aortic wall hypertrophy was obtained in all treated SHR. Trandolapril and verapamil-trandolapril combination produced a significant reduction of aortic collagen density compared with placebo SHR. Carotid total fibronectin, EIIIA fibronectin isoform and alpha5beta1 integrin, were higher in the media of placebo SHR than in WKY. EIIIA fibronectin isoform and alpha5beta1 integrin were reduced in verapamil-SHR compared with placebo-SHR and normalized in trandolapril and verapamil-trandolapril-SHR compared with WKY. SHR-placebo and SHR treated with either verapamil or trandolapril as single-drug treatment showed a 4-fold increase in total fibronectin compared to the WKY. Only SHR treated with verapamil-trandolapril combination had total fibronectin not significantly different from that of WKY. Carotid arterial distensibility increased only in verapamil-trandolapril treated rats. Multivariate analysis showed arterial distensibility to be negatively correlated to mean blood pressure (P < 0.0001) and total fibronectin (P < 0.01). In conclusion, chronic treatment with the verapamil-trandolapril combination significantly improved in vivo arterial distensibility in SHR. The most important effects of the combination on arterial mechanics compared to those of verapamil or trandolapril alone may have been the consequence of its stronger action on arterial pressure, arterial wall hypertrophy and total fibronectin density. However we suggest that, in addition to the structural effects, complete normalization of blood pressure is necessary to obtain normal arterial distensibility.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Nitric oxide synthase gene polymorphisms, blood pressure and aortic stiffness in normotensive and hypertensive subjects.

BACKGROUND: Genetic studies may help us to understand the mechanisms underlying the involvement of various neuro-humoral factors in the regulation of the mechanical properties of large arteries. We have shown previously that the angiotensin II type 1 receptor gene polymorphism was a strong determinant of aortic stiffness in hypertensives. OBJECTIVE: To assess the contribution of two polymorphisms of the endothelial nitric oxide synthase gene to aortic stiffness in normotensive and hypertensive subjects in the same cohort. METHODS: We studied 309 untreated hypertensive and 123 normotensive subjects. Aortic stiffness was evaluated by measuring the carotid-femoral pulse-wave velocity non-invasively. The endothelial nitric oxide synthase gene polymorphisms G10-T at intron 23 (GIN23T) and G298-T at exon 7 (Glu298Asp) were determined in each subject. RESULTS: The distributions of genotypes and allele prevalences of the endothelial nitric-oxide synthase G10-T polymorphisms among hypertensive and normotensive subjects were similar. In contrast, the prevalence of the nitric oxide synthase 298G allele was higher in the hypertensive group than it was among normotensive subjects. We found no association of the endothelial nitric oxide synthase genotypes with blood pressure levels or pulse-wave velocity for either population. CONCLUSIONS: The present results do not suggest that two common polymorphisms of the endothelial nitric oxide synthase gene are involved in the regulation of aortic stiffness in hypertensive and normotensive individuals. The higher prevalence of endothelial nitric oxide synthase 298G allele among hypertensives suggests that this gene is involved in essential hypertension but this observation needs further confirmation.

Adolescent↗

PubMed1998

Different effects of calcium antagonists on fluid filtration of large arteries and albumin permeability in spontaneously hypertensive rats.

OBJECTIVE: To compare the effects of chronic administration of two dihydropyridines, nifedipine and amlodipine, and the non-dihydropyridine Ca2+ antagonist mibefradil on fluid filtration of large arteries and extravasation of albumin in spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats aged 2 months were randomly allocated to oral treatment once a day with 30 mg/kg mibefradil (n=12), 100 mg/kg nifedipine (n=12), 20 mg/kg amlodipine (n=12) or placebo (n=12) for 1 month. Instantaneous blood pressure of rats under pentobarbital anaesthesia was recorded at the end of the treatment Fluid filtration across the carotid arterial wall was determined in situ in the isolated carotid artery. Extravasation of 25 mg/kg Evans Blue dye that had been injected intravenously was used to assess whole vascular permeability to albumin after chronic treatment with mibefradil. RESULTS: Similar reductions in mean arterial pressure were obtained in all Ca2+ antagonist-treated rats. Heart rate was similar in rats in control, nifedipine and amlodipine groups but was significantly lower in mibefradil-treated rats (by 19%, P< 0.001). Fluid filtration across the carotid wall was greater in all Ca2+ antagonist-treated animals. However, fluid filtration was significantly less in mibefradil-treated rats than it was in nifedipine-treated, and amlodipine-treated rats. Furthermore, administration of mibefradil did not significantly modify extravasation of albumin in all tested tissues (pancreas, testis, spleen, lung, kidney, intestine, liver, skeletal muscle) except for cardiac and brain tissues, in which the permeability of albumin was increased by 24 and 33%, respectively, compared with values for the control group (P < 0.05). CONCLUSION: These results indicate that Ca2+ antagonists increase fluid filtration through large arteries from spontaneously hypertensive rats. That the lower fluid filtration in mibefradil-treated rats was associated with no change in extravasation of albumin in most tissues and especially in skeletal muscle suggests that vascular permeability in hypertensive rats was impaired less by mibefradil treatment than it was by dihydropyridine Ca2+ antagonist treatments.

Amlodipine↗