elastin and Hypertension--Renal

Systemic hypertension affects many allograft recipients, is an important risk factor for chronic graft dysfunction, and is linked to reduced graft survival. The condition may up-regulate the expression of inflammatory host cells and their products. These, in turn, may significantly injure vascular endothelium and other components of allografted kidneys.. Lewis rats received orthotopic F344 renal allografts, a standard model of chronic rejection. Renovascular hypertension was produced by placing a silver clip (0.25 mm) on the renal artery of the retained contralateral native kidney 4 weeks after transplantation. Sham-clipped rats served as normotensive controls. Four recipient groups (Gp) were studied: Gp 1, rats with an allograft plus a clipped native kidney; Gp 2, those with an allograft and a sham-clipped native kidney; Gp 3, isografted animals with a clipped native kidney; and Gp 4, those bearing an isograft and a sham-clipped native kidney. Systolic blood pressure and proteinuria were measured every 2 weeks for 24 weeks. Grafts were assessed serially for morphologic and immunohistologic changes.. Systemic blood pressure rose to hypertensive levels in Gps 1 and 3 within a week of clipping but never increased in Gps 2 and 4. Proteinuria developed in hypertensive animals but remained at baseline in normotensive controls. Intimal thickening of allograft arteries progressed to luminal obliteration with extensive perivascular and interstitial fibrosis by 24 weeks. In contrast, vascular changes in isografts of hypertensive hosts were restricted to medial hypertrophy. Tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, platelet derived growth factor (PDGF), endothelin, Il-6, major histocompatibility complex (MHC) class II, and B7 were up-regulated in allografts in hypertensive hosts. Vascular deposition of immunoglobulin (IgG) was increased. These changes were markedly less pronounced in Gp 3 isografts and minimal in the kidneys of the normotensive animals of Gps 2 and 4.. An experimental model is presented that examines the influence of recipient hypertension in the pathogenesis of chronic dysfunction and injury developing in rat renal allografts over time.

Topics: Animals; Biomarkers; Blood Pressure; Elastin; Graft Survival; Hypertension, Renal; Hypertrophy; Kidney Transplantation; Male; Rats; Rats, Inbred F344; Rats, Inbred Lew; Rats, Sprague-Dawley; Transplantation, Homologous; Transplantation, Isogeneic

The purpose of this study was to examine effects of hypertension on mechanics of cerebral arterioles in nongenetic and genetic models of chronic hypertension. Pressure (servo null) and diameter were measured in pial arterioles of anesthetized renal hypertensive rats (one-kidney, one clip), uninephrectomized normotensive rats, spontaneously hypertensive rats, and normotensive Wistar-Kyoto rats. During maximal dilatation with EDTA, external diameter of pial arterioles at 70 mm Hg pial arteriolar pressure was not significantly different in renal hypertensive and normotensive rats (86 +/- 5 [mean +/- SEM] versus 84 +/- 4 microns) but was less in spontaneously hypertensive rats than in Wistar-Kyoto rats (81 +/- 3 versus 92 +/- 3 microns; p < 0.05). Cross-sectional area of the arteriolar wall (histological) was greater in renal hypertensive than in normotensive rats (1,360 +/- 131 versus 952 +/- 89 microns 2; p < 0.05) and in spontaneously hypertensive rats than in Wistar-Kyoto rats (1,294 +/- 97 versus 817 +/- 86 microns 2; p < 0.05). The stress-strain relation obtained from pressure-diameter data during maximal dilatation with EDTA indicated that distensibility of pial arterioles, when fully relaxed, was greater in renal hypertensive and spontaneously hypertensive rats than in normotensive and Wistar-Kyoto rats. We used point-counting stereology to quantitate composition of pial arterioles in renal hypertensive rats. Cross-sectional area of smooth muscle and elastin was significantly greater in renal hypertensive than in normotensive rats (smooth muscle, 947 +/- 108 versus 620 +/- 62 microns 2; elastin, 101 +/- 11 versus 55 +/- 6 microns 2; p < 0.05), whereas cross-sectional area of collagen and basement membrane was not significantly different in the two groups (collagen, 6 +/- 1 versus 5 +/- 1 microns 2; basement membrane, 120 +/- 12 versus 104 +/- 8 microns 2). Thus, we conclude that 1) cerebral arterioles undergo hypertrophy in both renal hypertensive and spontaneously hypertensive rats; 2) cerebral arterioles in renal hypertensive rats do not undergo "remodeling" with a reduction in external diameter, whereas external diameter is smaller in spontaneously hypertensive than in Wistar-Kyoto rats; 3) distensibility of cerebral arterioles, when fully relaxed, is increased in renal hypertensive rats and is greater in spontaneously hypertensive than in Wistar-Kyoto rats; and 4) the distensible components of the arteriolar wall are increased disproportionately i

Topics: Animals; Arterioles; Cerebrovascular Circulation; Elastin; Hypertension, Renal; Muscle, Smooth, Vascular; Pia Mater; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley

One of the well-known consequences of established hypertension is an increase in connective tissue proteins in the walls of the large arterial blood vessels. Using renal clip and Dahl salt-sensitive rat models of systemic hypertension, we investigated the effect of developing hypertension on elastin production and accumulation in rat aorta. In both models of hypertension, increased accumulation of arterial elastin appeared coincidentally with, and was proportional to, elevation of blood pressure. In spite of large increases in absolute amounts of elastin, the proportion of elastin present in the vessel wall remained essentially constant from the earliest stage of the response. These changes in elastin synthesis and accumulation took place in the absence of evidence of cell proliferation. Treatment of Dahl rats with colchicine during development of hypertension affected blood pressure rise only marginally but abolished the vascular hypertrophic response. Our results suggest that the response of elastin production to increased blood pressure is rapid and sensitive, and that the stimulus for increased synthesis is an increase in wall stress. The striking effect of colchicine may indicate a role of elements of the cytoskeleton in the perception of stress by the vascular smooth muscle cells or in the transduction of that stress into increased production of connective tissue proteins.

Topics: Animals; Aorta; Colchicine; DNA; Elastin; Hypertension; Hypertension, Renal; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred Strains; Reference Values; Time Factors

The collagen and elastin contents of the major arterial components of the canine circle of Willis (basilar artery, posterior cerebral artery, internal carotid artery, middle cerebral artery, and anterior cerebral artery) were determined as measures of the passive mechanical properties of these vessels. Studies were carried out in seven normotensive dogs and seven dogs in which experimental renal hypertension of 3 months duration had been induced. In the normotensive animals, the collagen content of the middle cerebral artery exceeded that of the other vessels considered. The elastin content and the total connective tissue were not significantly affected by arterial site. The middle cerebral artery collagen to elastin ratio was greater than corresponding values for the basilar, posterior cerebral, and internal carotid arteries. Connective tissue differences were less pronounced in the hypertensive animals. No component of the canine circle of Willis in the hypertensive dogs showed a significantly different collagen content, elastin content, total connective tissue content, or collagen to elastin ratio. In comparing cerebral vessels from normotensive and hypertensive dogs, total connective tissue values were greater in hypertension for all arterial sites considered. These acute physiological changes in connective tissue content over small distances in intracranial blood vessels from normotensive animals, together with unique connective tissue responses of these vessels to short term hypertension, may suggest additional possible factors important in the natural history of cerebrovascular pathological conditions.

Topics: Animals; Cerebral Arteries; Circle of Willis; Collagen; Connective Tissue; Dogs; Elastin; Hypertension, Renal

Topics: Animals; Aorta, Thoracic; Atrophy; Collagen; Connective Tissue; Corticosterone; Elastin; Hypertension, Malignant; Hypertension, Renal; Leukocyte Count; Male; Rats; Rats, Inbred Strains; T-Lymphocytes; Thymus Gland

Vascular structural changes were studied during the development of two-kidney one-clip renal hypertension. The weight of the arteries and the concentration and total amount of ribonucleic acid, deoxyribonucleic acid, alkali-soluble proteins, collagen and elastin of the vascular wall were measured. Tritiated thymidine uptake was also determined 15 and 30 days after clipping. Hypertension developed in 58% of the animals while the rest remained normotensive. A significant increase in artery weight and in the total amount of nucleic acids and proteins was found in hypertensive rats. The uptake of 3H thymidine by the arteries of hypertensive rats was significantly increased 15 days after clipping. This increment showed a significant correlation with blood pressure levels. Present data seem to indicate that the increase in vessel wall dimensions observed is partly due to an increase in the number of smooth muscle cells during the acute phase; this alteration appears to be mainly due to the rise in blood pressure.

Topics: Animals; Blood Pressure; Cardiomegaly; Collagen; Disease Models, Animal; DNA; Elastin; Hyperplasia; Hypertension, Renal; Hypertension, Renovascular; Male; Muscle, Smooth, Vascular; Myocardium; Rats; Rats, Inbred Strains; RNA; Thymidine

Segments of carotid and tail arteries were used to determine the effects of two-kidney Goldblatt hypertension on mechanical properties and chemical contents. Arteries were obtained after 4 and 12 wk of hypertension. Systolic pressures averaged 129 mmHg in control animals and 150 mmHg in hypertensive ones. Pressure-diameter data were recorded under conditions of active (145 mM K+) and passive (0 Ca2+ and 2 mM EGTA) smooth muscle. Small increases in passive stiffness were found after 4 and 12 wk in the carotid arteries of hypertensive animals, but no significant change occurred in the tail arteries. Small but significant decreases in total connective tissue content of these arteries were found after 12 wk of hypertension. Maximum values of active stress response were significantly larger in carotid arteries from hypertensive animals at both 4 and 12 wk of hypertension. No significant differences were found for the tail arteries. The K+ content of the carotid but not the tail artery was larger for the hypertensive animals. When corrected for differences in relative cell content most of the differences in active force development were eliminated. The differences in passive mechanics can not be explained on the basis of the changes in connective tissue content. The active smooth muscle responses and content changes suggest that they are directly related to the moderate elevation of arterial pressure.

Topics: Animals; Arteries; Body Water; Collagen; Elastin; Extracellular Space; Hypertension, Renal; Male; Mathematics; Muscle, Smooth, Vascular; Potassium; Rats; Time Factors

Vessels of known position in the vascular tree of the kidneys of two cases with a long history of progressive systemic sclerosis--one normotensive, one hypertensive--were examined morphometrically. Medial thickness, intimal thickness and the relative content of collagen and elastin in the vascular media were measured. Smooth muscle nuclei were counted in the arterial cross section. These morphometric data were compared with those obtained from two autopsy cases--one with a history of essential hypertension, one without any hypertensive history. The findings suggest that progressive sclerosis induces intimal thickening in all branches of the renal artery down to a distented diameter of 200 microns. In the case where progressive sclerosis was complicated by arterial hypertension increased medial thicknesses were found, similar to the findings in the case with a history of essential hypertension.

Topics: Arteries; Cell Nucleus; Collagen; Elastin; Female; Humans; Hypertension, Renal; Kidney; Middle Aged; Muscle, Smooth; Renal Artery; Scleroderma, Systemic

The authors examined neosynthesis of fiber proteins (scleroproteins) in the aorta of rats with genetic hypertonia and with experimental atherosclerosis after application of 3H-proline and 3H-lysine and subsequent determination of radioactivity of collagenous and elastic in the aortic wall. There was a great increase in incorporation a labelled precursors of collagen and elastin in the aorta of hypertonic and atherosclerotic animals in comparison with the control rats-a manifestation of increased "de novo" synthesis of fiber proteins in rats with these arterial diseases. Furthermore the increased collagenosis dominated over that of elastogenesis. The irregularity in the activation of biosynthesis of both sclero-proteins in rats with hypertonia and atherosclerosis caused remodeling of macromolecular structure of the aretrial wall with a predominance of collagen over the remaining components of the connective tissue matrix. The resulting fibrosis of the arterial wall favoured the fixation of hypertonia and progression of atherosclerosis.

Topics: Animals; Aorta; Arteriosclerosis; Collagen; Elastin; Hypertension; Hypertension, Renal; Lysine; Proline; Protein Biosynthesis; Rats; Rats, Inbred Strains

Topics: Animals; Blood Pressure; Carotid Arteries; Collagen; Elasticity; Elastin; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Muscle, Smooth; Norepinephrine; Rats

Topics: Age Factors; Animals; Animals, Newborn; Aorta; Blood Pressure; Collagen; Elastin; Hypertension, Renal; Rabbits

Topics: Analysis of Variance; Animals; Aorta; Blood Pressure; Calcinosis; Calcium; Collagen; Connective Tissue; Elastin; Hypertension, Renal; Phosphates; Probability; Proteins; Rabbits; Regression Analysis; Vitamin D

Topics: Aldosterone; Animals; Aorta; Carbon Isotopes; Chromatography, Ion Exchange; Collagen; Elastin; Hydroxyproline; Hypertension, Renal; Male; Proline; Rats

Topics: Animals; Aorta; Arteries; Blood Pressure; Blood Urea Nitrogen; Collagen; Connective Tissue; Dogs; Elastin; Hypertension, Renal