Abstract-Although the role of sodium in hypertension has been documented extensively, its effect on large arteries has not been well documented. We examined the effect of high-sodium (8%) diet and the diuretic indapamide (IND) on systemic hemodynamics and aortic wall structure and composition in collagen, elastin, and hyaluronan. Four groups of spontaneously hypertensive rats (SHR) were studied after 8 weeks: those on a normal diet (SHR), a high-sodium diet (SHRϩNaCl), a normal diet with IND (SHRϩIND), and a high-sodium diet with IND (SHRϩNaClϩIND). Mean BP, which was not normalized with IND, was comparable for all groups. Systemic arterial compliance averaged 3.8, 2.5, 4.9, and 3.3 mL/mm Hg · 10 Ϫ3 , respectively, for the SHR, SHRϩNaCl, SHRϩIND, and SHRϩNaClϩIND groups (PϽ0.003 and Ͻ0.05 for NaCl and IND effects). Wall thickness increased only in the SHRϩNaCl group (PϽ0.01). Aortic wall COL decreased from 16 116 in the SHR to 12 382 m 2 /mm in the SHRϩNaClϩIND (PϽ0.005) group. IND alone had no effect on elastin, but the elastin/collagen ratio was increased significantly. Aortic hyaluronan averaged 2343, 266, 3243, and 1052 m 2 /mm, respectively, for the SHR, SHRϩNaCl, SHRϩIND, and SHRϩNaClϩIND groups (PϽ0.0001 for NaCl and IND effects). Changes in systemic arterial compliance were significantly and positively correlated with aortic hyaluronan contents. Thus, high-sodium diet affects the structural and functional characteristics of large arteries independently of BP. A high-sodium diet, in addition to a diuretic regimen with IND, affects simultaneously aortic hyaluronan contents and large artery mechanical properties through pressure-independent mechanisms that remain to be defined. Key Words: arteries Ⅲ diet Ⅲ diuresis Ⅲ proteoglycans Ⅲ rats, spontaneously hypertensive E pidemiological studies indicate that in populations of normotensive and hypertensive subjects, a strong association is observed between high sodium intake and increased aortic rigidity, independent of both age and BP level. 1 Conversely, reduced sodium intake is associated with enhanced arterial elasticity. 2 In hypertensive rats, high sodium intake leads not only to cardiac hypertrophy and fibrosis but also to hypertrophy of large arteries and enhanced extracellular matrix, again independently of BP level. 3 However, the potential link between such structural alterations and the mechanical properties of the arteries has not been investigated extensively.During high sodium intake in experimental animals, concentration of this cation in the vascular smooth muscle cell rises, but most of it remains extracellularly bound to the interstitial matrix, probably to polyanionic mucopolysaccharides. 4 To our knowledge, whether such macromolecules contribute to mechanical properties of the arteries during high sodium intake has never been reported under in vivo conditions, at least for large conduit arteries. In sodium-dependent hypertensive animal models, diuretics reduce hypertrophy of the arterial wall even if BP remains unchanged. 2 Interestingly, a c...
In this review paper, the classical and more recently described mechanisms responsible for the structural and functional characteristics of large artery rigidity are described. Mostly important, these characteristics appear to be non-specific to the primary disease process involved in arterial hypertension, diabetes mellitus, dyslipidemia, congestive heart failure, chronic uremia, and perhaps senescence, including vascular dementia. Nonspecific in terms of aetiology, the vasculopathy encountered in these diseases exhibits common structural and functional abnormalities. The identification of such abnormalities could well become the target of potent nonpharmacological and (or) pharmacological interventions capable of preventing or retarding morbidity and mortality. The structural characteristics responsible for large artery rigidity include smooth muscle cell hypertrophy, matrix collagen deposition, and recently described, dysfunction in proteoglycan metabolism. Functional abnormalities, such as bradykinin-dependent hyper-reactivity of smooth muscle cells and vasa vasorum microcirculation network disturbances, also appear to alter aortic wall rigidity. The physiopathology of target organ damage is then revisited, based on endothelial dysfunction, documented in large and resistance arteries, as well as in microcirculation networks, where altered permeability to macromolecules leads to interstitial matrix disorganization and cell damage. The clinical evaluation of large artery rigidity is described, and one of the noninvasive methods, evaluation of pulse-wave velocity, is validated in normal conditions and in disease processes. Finally, non-pharmacological and pharmacological therapeutic measures are presented, and includes physical exercise to reduce insulin resistance, and renin-angiotensin-II-aldosterone modulators.
In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.
In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.
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