Histopathological changes in the wall of varicose veins.

AIM: Vein wall distensibility is controlled by collagen, elastin and smooth muscle cells. However, contradicting evidence exists on the connective tissue concentration and smooth muscle pathology in varicose veins. METHODS: To study the pathological changes in the wall of varicose veins at different levels, we collected a total of 49 vein specimens from 19 patients at Asir Central Hospital, Abha, Saudi Arabia, during the period from March to October 1997. Three young trauma patients underwent repair of their arterial injuries using the thigh long saphenous vein (LSV) and 16 varicose vein patients underwent stripping of their LSV and avulsion of their distal calf varicosities. In the trauma patients, specimens were collected from the proximal thigh LSV while in the varicose vein patients, specimens were collected from both the groin and mid-thigh LSV and the distal calf varicosities. Specimens were stained with Hematoxylin & Eosin, Masson's Trichrome and von Gieson (VG) stains for examination under the light microscope. RESULTS: Compared with the normal LSV, all varicose vein sections showed marked intimal hypertrophy due fibrous tissue infiltration, localized thinning of the muscle layer and loss of both the intimal and medial smooth muscle cells (SMCs). Elastic fibers were deficient and scattered with loss of the normal elastin/collagen lattice network and decrease in both the muscle/collagen and elastin/collagen ratios. CONCLUSION: In conclusion, we propose that dilatation and distensibility of the vein wall under normal and increased venous pressure is due to deficiency in smooth muscle cells and elastic fibers and disproportionate increase in fibrous tissue.     

Evaluation of medial hypertrophy in resistance vessels of spontaneously hypertensive rats

The role of smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in medial hypertrophy of mesenteric resistance vessels of 107- to 111-day-old spontaneously hypertensive rats (SHR) was examined using a combination of morphometric, biochemical, and immunological techniques. Mesenteric arteries were classified on the basis of branching order for comparative purposes. Branch level I vessels were those that directly enter the jejunal wall, while Branches II to IV represented more proximal vessels; Branch IV vessels were those that branch from the superior mesenteric artery. Medial hypertrophy was assessed in perfusion-fixed vessels by morphometric evaluation of medial cross-sectional area and smooth muscle content. Medial cross-sectional area and smooth muscle content were significantly increased in larger (Branches III and IV) but not smaller (Branches I and II) mesenteric resistance vessels of SHR compared with control normotensive Wistar-Kyoto rats (WKY). Smooth muscle cell hypertrophy and hyperploidy were evaluated in isolated cells obtained by enzymatic dissociation of mesenteric resistance vessels. Approximately 80% of the cells in these preparations were identified as smooth muscle cells using a smooth muscle-specific isoactin antibody. Feulgen-DNA microdensitometric evaluation of isolated cells showed that polyploid cells were present in mesenteric resistance vessels but at very low frequencies, and no differences were apparent between SHR and WKY. Likewise, no differences in cellular protein content or relative smooth muscle cell size (i.e., area profile) were observed between cells obtained from SHR and WKY vessels. These results demonstrate that the increase in medial smooth muscle content observed in larger mesenteric resistance vessels of SHR cannot be accounted for by smooth muscle hypertrophy and hyperploidy, inferring that hyperplasia must be present. Results indicate that studies of the initiating mechanisms for medial smooth muscle hypertrophy in SHR resistance vessels, at least relatively early in hypertension, should focus on examination of factors that induce true cellular proliferation rather than hypertrophy and hyperploidy.     

Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension

The effect of hypertension and of therapy by converting enzyme inhibitor (S 9490-3, perindopril) on the function and structure of large arteries has been studied in two-kidney, one-clip Goldblatt hypertensive rats. After one month without treatment, clipped hypertensive rats (n = 24) and sham-operated rats (n = 24) were randomly allocated to treatment by S 9490, 1 mg/kg once a day (n = 24) or to placebo (n = 24) and pursued for 4 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity measured by D?ppler, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were recorded in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Morphological parameters of the aortic media, including medial thickness, nucleus density, and cross sectional area and relative density in proteins of interstitial matrix, were recorded by an automated morphometrical system. Hypertension was associated with an increase in characteristic impedance of the aorta and a decrease in compliance of the arterial system. Treatment with converting enzyme inhibitors completely reversed these in vivo markers of the rigidity of large arteries. Hypertension was associated with a shift of the passive pressure-volume relation in the carotid. Treatment with converting enzyme inhibitors normalized the carotid pressure-volume relation, whereas poisoning smooth muscle cells induced a disappearance of the curve differences between hypertensive and normotensive animals. Morphometric analysis of aortic walls permits us to report this functional change to structural modification of the arterial wall. Aortic media thickness was increased by hypertension; this phenomenon was reversed by treatment. Modification of aortic thickness was due to hypertrophy of smooth muscle cells with parallel modifications of absolute amount of collagen, whereas absolute amount of elastin did not change in this early phase of renovascular hypertension in young rats. Treatment with converting enzyme inhibitors reversed the thickness of aortic media without regression of the increase in absolute amount of collagen content whereas absolute amount of elastin content did not change.     

Relation of intra-acinar arteries and their regression with changes of pulmonary artery pressure and blood gas values

Pulmonary hypertension (PAH) induced by monocrotaline in thirteen rhesus monkeys, seven of them treated by hydralazine to reduce PAH. In hypertensive animals the PAP and PaCO2 increased, the PaO2 decreased. The structural changes in intra-acinar artery manifested mainly by an increase in number of muscular artery resulting from muscularization of precursor cells (pericytes and intermediate cells) located within partially muscular and nonmuscular arterial wall to smooth muscle cell, and by the medial wall thickened due to hypertrophy and hyperplasia of smooth muscle cells as well as accumulation of a large amount of collagen, especially the type 1 collagen. In treated animals the PAPm dropped concomitantly with blood gas values reversing to normal level. The remodelled arteries showed clearly structural regressions: The medial wall thickness was decreased in which the hypertrophied smooth muscles became slender or disappeared, the amount of extracellular matrix, especially the volume density of collagen, decreased. Most of muscularized arteries reversed to nonmuscular arteries leading to an increase in number of nonmuscular artery and a decrease in number of muscular artery. It is concluded that the intra-acinar artery remodelling and their regression closely correlated with the changes of PAP and blood gas values.     

Evidence of Early Structural Change in the Artery Wall of Two-Kidney One-Clip Goldblatt Hypertensive Rats

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.     

Collagen and elastin metabolism in hypertensive pulmonary arteries of rats

We evaluated the processes controlling the accumulation of collagen and elastin in main pulmonary arteries of rats during an episode of hypoxic pulmonary hypertension. Explant cultures of main pulmonary arteries were incubated with [3H]proline to measure collagen and protein synthesis and percent collagen synthesis. Elastin synthesis was measured by [14C]valine incorporation into insoluble elastin. Relative collagen synthesis increased twofold (from 1.1 +/- 0.2 x 10(3) to 2.0 +/- 1.0 x 10(3) disintegrations per minute [14C]hydroxyproline/vessel/hr/mg protein), relative collagen synthesis doubled (from 2% to 4-5% of total protein synthesis), and elastin synthesis increased ninefold (from 0.4 +/- 0.2 x 10(4) to 3.6 +/- 0.6 x 10(4) dpm [14C]valine/vessel/hr/mg protein) in early hypertension. The level of pro alpha l(I) collagen RNA paralleled the relative collagen synthetic rate during the study period. Within 7 days of recovery from hypoxia, collagen and elastin contents were normal. We conclude that collagen and elastin in main pulmonary arteries are synthesized rapidly during an episode of hypoxic pulmonary hypertension and that collagen and elastin are rapidly removed from the hypertensive vessel during normoxic recovery.     

Mechanisms underlying hypertrophic remodeling and increased stiffness of mesenteric resistance arteries from aged rats

The mechanisms associated with structural and mechanical alterations of mesenteric resistance arteries from aged rats were investigated by using pressure myography, confocal microscopy, immunofluorescence, and picrosirius red staining. Arteries from old rats showed: (i) increased wall and media thickness, greater number of smooth muscle cell (SMC) layers but decreased density of SMC; (ii) increased number of adventitial cells; (iii) hypertrophy of nuclei of SMC and endothelial cells; (iv) increased stiffness associated with increased total collagen content and collagen I/III deposition in the media; and (v) similar content but changes in elastin structure in the internal elastic lamina. Hypertrophic outward remodeling in aged rat resistance arteries involve adventitial cells hyperplasia, reorganization of the same number of hypertrophied SMC in more SMC layers leading to thickened media and endothelial cell hypertrophy. Fibrosis associated with collagen deposition and changes in elastin structure might be responsible for the increased stiffness of resistance arteries from aged rats.     

Stimulation of fibroblast collagen and total protein formation by an endothelial cell-derived factor

We investigated the effect of medium conditioned by bovine aortic endothelial cells on collagen accumulation and total protein formation by human embryonic fibroblasts or bovine smooth muscle cells in cultures. The conditioned medium at a 1:10 dilution induced a twofold increase in collagen and total protein accumulation in fibroblast cultures. At low concentration (1:50 dilution), the conditioned medium stimulated collagen accumulation preferentially; at high concentration (1:10 dilution), overall protein synthesis also was increased. The increase in type I collagen accumulation was associated with an increase in the steady-state level of alpha 1 (I) mRNA for collagen. The conditioned medium increased the production of types I and III collagen without affecting the proportion of collagen types in both fibroblast and smooth muscle cell cultures. Partial purification of the endothelial cell-derived factor disclosed it to be a heat-stable protein with an apparent molecular weight of 8-10 kDa. The stimulation of protein formation by this substance was not inhibited by antibodies against transforming growth factor-beta or the insulinlike growth factor I receptor. The partially purified factor stimulated protein production without affecting fibroblast proliferation. This endothelial cell-derived protein may play a role in the remodeling of vascular connective tissue by stimulating collagen synthesis.     

Hypertensive arteriopathy and atherogenesis: cellular and molecular interactions

The spontaneously hypertensive rat (SHR)--animal model for human essential hypertension--develops a generalized arteriopathy. The present paper discusses the atherogenic influence of hypertensive arterial lesions. The following changes in the intima might influence its permeability and barrier function, increase the trapping effect and stimulate the smooth muscle cell proliferation: the hyper-reactivity of endothelial cells; the decreased thickness of endothelial cell periphery; the reduced intercellular junction pathways; the increase in basal lamina and glycosaminoglycan sub-endothelial material; the mononuclear cell infiltrations; the widened fenestrae in the internal elastic lamina. Some hypertensive changes of the tunica media may also interact with atherogenic process through reduced smooth muscle cell lipolytic capabilities, slowed transmural diffusion, perturbed efflux, aggravated media hypoxia, namely: the decrease in esterase and cholinesterase activities, the activations of some lysosomal enzymes, the increase in collagen, glycosaminoglycan and elastin content; the increased media thickness and transmural passage; the modified smooth muscle cell behavior.     

Collagen triple helix repeat containing 1, a novel secreted protein in injured and diseased arteries, inhibits collagen expression and promotes cell migration

Collagen triple helix repeat containing 1 (Cthrc1) was identified in a screen for differentially expressed sequences in balloon-injured versus normal arteries. Cthrc1 expression was not detectable in normal arteries. However, on injury it was transiently expressed by fibroblasts of the remodeling adventitia and by smooth muscle cells of the neointima. It was also found in the matrix of calcifying human atherosclerotic plaques. CTHRC1 is a secreted 28-kDa protein that is glycosylated and highly conserved from lower chordates to mammals. A short collagen motif with 12 Gly-X-Y repeats appears to be responsible for trimerization of the protein and this renders the molecule susceptible to cleavage by collagenase. Cthrc1 mRNA expression levels are increased in response to transforming growth factor-beta and bone morphogenetic protein-4. Cell migration assays performed with CTHRC1-overexpressing fibroblasts and smooth muscle cells demonstrate that increased CTHRC1 levels are associated with enhanced migratory ability. Furthermore, CTHRC1 overexpression caused a dramatic reduction in collagen type I mRNA and protein levels. Our data indicate that the novel molecule CTHRC1 is transiently expressed in the arterial wall in response to injury where it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration.     

硫化氢对低氧性肺动脉高压大鼠细胞因子的调节作用

目的探讨硫化氢对低氧性肺动脉高压大鼠细胞因子的调节作用。方法将Wistar大鼠22只随机分为3组。对照组(8只),低氧组(7只),低氧+硫氢化钠(NaHS)组(7只),测定3组大鼠肺动脉平均压(mPAP),观测肺血管结构变化,并用免疫组织化学方法研究α-平滑肌肌动蛋白(-αSM-actin)、弹力蛋白、转化生长因子β(TGF-β)和结缔组织生长因子(CTGF)在肺动脉平滑肌细胞的表达含量。结果低氧组的mPAP明显高于对照组和低氧+NaHS组;低氧组肌型动脉、部分肌型动脉百分比明显高于对照组和低氧+NaHS组,非肌型动脉百分比明显低于对照组和低氧+NaHS组;低氧组肺中、小型肺动脉平滑肌细胞-αSM-actin、弹力蛋白和TGF-β表达含量分别明显高于对照组和低氧+NaHS组;对照组、低氧+NaHS组以及低氧组肺中、小型肺动脉平滑肌细胞CTGF表达含量依次增高,但3组之间无显著差异。结论硫化氢可能通过调节低氧性肺动脉高压大鼠肺小血管肌性动脉TGF-β的表达,进而抑制细胞外基质成分之一的弹力蛋白合成,参与低氧性肺动脉高压的形成。     

Ito-cell gene expression and collagen regulation

Ito cells are perisinusoidal cells thought to be a major source of collagen in normal and fibrotic livers. These cells appear to have features similar to several cell types but when cultured assume a fibroblast-like morphology. In this study we evaluated the phenotype of both freshly isolated and cultured Ito cells by examining their gene expression. To better define the modulators of Ito-cell collagen synthesis, we also examined the effect of transforming growth factor-beta 1, tumor necrosis factor-alpha and dexamethasone on collagen synthesis by these cells. Northern hybridization analysis revealed that cultured Ito cells expressed different types of procollagen mRNAs than did freshly isolated cells. Cultured cells contained large amounts of type I procollagen mRNA and lesser amounts of types III and IV, whereas freshly isolated cells contained more type IV procollagen mRNA than types I and III. Treatment of cultured cells with either transforming growth factor-beta 1 or tumor necrosis factor-alpha resulted in a greater than three-fold increase in total collagen content, and the effects of these cytokines on Ito-cell collagen synthesis involved different levels of gene regulation. Transforming growth factor-beta 1-treated cells had an approximately threefold increase in their type I procollagen mRNA levels, whereas no increase in this mRNA level was found in tumor necrosis factor-alpha-treated cells. Transforming growth factor-beta 1 treatment induced a twofold increase in transforming growth factor-beta 1 mRNA content in cultured cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of spontaneous hypertension and age on arterial connective tissue in the rat

Weights of aorta and heart and accumulation of collagen and elastin in aorta were determined in spontaneously hypertensive and control Wistar rats of 14 weeks, six months, one year and 18 months of age. It was found that in control rats weights of aorta and heart increased as a function of age but when expressed as percent of body weight there was no change with age. However, changes in SHR's were more marked, with the aortic and heart weights increasing progressively with age to a much greater extent than in control rats. Expressed as percent body weight, aortic weight increased progressively in SHR and heart weight increased by 18 months indicating hypertrophy of the cardiovascular system in the SHR with age.

Absolute quantities of connective tissues increased in aorta in both control and hypertensive rats with age. However, the accumulation was more marked in hypertensive. If connective tissue is expressed as percent of aortic weight, collagen plus elastin actually decreased as a function of age in control and to a much greater extent in SHR. The results indicate (1) increased accumulation of connective tissue in aortae of rats with age and even greater increase in aortae of hypertensive rats with age. (2) Increase in aortic smooth muscle mass with age in control and even greater increase in hypertensive aortae. It is concluded that long term spontaneous hypertension in the rat results in an increase over control rats in the major aortic wall components with smooth muscle increase greater than connective tissue increase. These changes occur in late stages of hypertension as well as early stages.     

Dipeptidyl Peptidase IV Regulates Proliferation of Preglomerular Vascular Smooth Muscle and Mesangial Cells

The purpose of this study was to investigate the role of dipeptidyl peptidase IV in regulating the effects of 2 of its substrates, neuropeptide Y(1-36) and peptide YY(1-36), on proliferation of and collagen production by preglomerular vascular smooth muscle and glomerular mesangial cells from spontaneously hypertensive and normotensive rats. In cells from hypertensive rats, neuropeptide Y(1-36) and peptide YY(1-36) stimulated [(3)H]-thymidine incorporation (cell proliferation index), cell number, and [(3)H]-proline incorporation (index of collagen synthesis); and sitagliptin (dipeptidyl peptidase IV inhibitor) significantly enhanced most of these effects. Neuropeptide Y(3-36) and peptide YY(3-36) (products of dipeptidyl peptidase IV) had little effect on [(3)H]-thymidine incorporation, and sitagliptin did not enhance the effects of either peptide. BIBP3226 (Y(1) receptor antagonist) blocked the effects of neuropeptide Y(1-36) and peptide YY(1-36) on [(3)H]-thymidine incorporation in the absence and presence of sitagliptin. Neuropeptide Y(1-36) and peptide YY(1-36) stimulated [(3)H]-thymidine and [(3)H]-proline incorporation and cell number in cells from normotensive rats; however, the effects were weak and mostly not affected by sitagliptin. Real-time PCR and Western blotting showed similar dipeptidyl peptidase IV mRNA and protein levels in cells from hypertensive versus normotensive rats, with greater levels in smooth muscle versus mesangial cells. Both cell types converted peptide YY(1-36) to peptide YY(3-36) in a concentration-dependent manner that was attenuated by sitagliptin, and dipeptidyl peptidase IV activity was greater in smooth muscle versus mesangial cells. In conclusion, dipeptidyl peptidase IV inhibitors might entail a risk of renal dysfunction because of abnormal proliferation of cells in the preglomerular microcirculation and glomeruli.     

Ultrastructural changes in mesenteric arteries from spontaneously hypertensive rats. A morphometric study

Morphometric measurements at the electron microscope level were carried out on three categories of mesenteric arteries representing elastic (superior mesenteric), muscular and arteriolar vessels, from 10- to 12-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto normotensive rats (WKY). Changes were observed only in muscular and arteriolar vessels of SHR, mainly as thickening of the vessel wall due to hypertrophy of the media. In muscular arteries, hypertrophy of the endothelial cells, widening of the subendothelial space, increased volume of the internal elastic lamina (IEL), and both hyperplasia and hypertrophy of the smooth muscle cells (SMC) in the media contributed to the wall thickening. In arteriolar vessels, increase in the subendothelial space and IEL, and hyperplasia of the SMC in the media were involved in the increased thickness of the vessel wall. There was no difference in the collagen content in all vessels, but elastin was increased in the muscular and arteriolar vessels of SHR. Nerve density was also increased in arteriolar vessels of SHR. These changes, especially the increase of SMC in muscular and arteriolar vessels, may be related to the elevated blood pressure in SHR.     

Abdominal aortic aneurysms: Distribution of elastin,collagen I and III,and intermediate filament proteins desmin and vimentin—A comparison of familial and nonfamilial aneurysms

Summary The aortic walls of patients with abdominal aortic aneurysms (AAA) and of healthy controls were examined for elastin, collagen I and III, and the intermediate filament proteins desmin and vimentin by immunohistochemical, enzyme histochemical, and routine histological techniques. The morphology of the aneurysmatic walls varied considerably from case to case, but many pathological changes were seen in all cases, e.g., extensive atherosclerotic plaques in the intima, prominent alterations in amount and organization of the elastic lamellae in the media, and an increase of connective tissue. Both collagen I and III were present in all the aneurysmatic walls. The smooth muscle cells in all the aortic walls showed a marked heterogeneity with respect to the morphological appearance, the enzyme histochemical features, and the content of desmin and vimentin. Vimentin occurred in some intimal, medial muscle, and adventitial cells of both the controls and the AAA patients. Desmin occurred in some of the intimal, medial, and adventitial muscle cells of both the controls and the AAA patients. All the cells with desmin in the intima and media also contained vimentin. Thus, smooth muscle cells in the walls of both the normal human abdominal aorta and aneurysms contained either vimentin, desmin, or both. This variability may be explained by the presence of different phenotypes of smooth muscle cells and could be of significance for the development of atherosclerosis and aneurysms. Of special interest was the finding that 5 of the 24 AAA patients studied had blood relatives with the same disease, suggesting a hereditary influence. However, no systematic differences between the morphological appearance of the aneurysmatic walls in familial and nonfamilial AAA could be detected.     

Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation

We identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene expressed in the adventitia and neointima on arterial injury and found that it functionally increases cell migration while reducing collagen deposition. To address the in vivo role of Cthrc1, we generated transgenic mouse lines that constitutively overexpress Cthrc1. An intercross of 2 transgenic lines produced offspring with brittle bones caused by a reduction in collagenous bone matrix. Hemizygous Cthrc1 transgenic mice developed normally but neointimal lesion formation and adventitial collagen deposition in response to carotid artery ligation were significantly reduced compared with wild-type littermates. In 75% of Cthrc1 transgenic mice, cartilaginous metaplasia of medial smooth muscle cells was observed as assessed by Alcian blue staining and expression of the chondrocyte marker collagen type II. Transforming growth factor-beta signaling was reduced in smooth muscle cells of Cthrc1 transgenic arteries, as demonstrated by reduced phospho-Smad2/3 immunoreactivity, whereas Smad signaling related to bone morphogenetic proteins was unaffected. Similarly, primary smooth muscle cells and PAC1 smooth muscle cells overexpressing Cthrc1 had reduced levels of phospho-Smad2/3 as well as procollagen. Furthermore, Cthrc1 inhibited transforming growth factor-beta-sensitive reporter constructs in smooth muscle but not endothelial cells. These data indicate that Cthrc1 is a cell-type-specific inhibitor of transforming growth factor-beta, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of smooth muscle cells.     

Effects of hypertension and its reversal on canine arterial wall properties

Segments of carotid, femoral, saphenous, and left circumflex coronary arteries were obtained from control, renal hypertensive, and nephrectomized hypertensive dogs for in vitro study of mechanical properties. Hypertension was produced in two-kidney dogs by unilateral renal artery constriction. After 3 months, the compromised kidney was removed in half of the dogs. Mean arterial pressure was significantly elevated in the hypertensive dogs after 3 months (127 +/- 2 vs 94 +/- 1 mm Hg for controls) and partially returned toward normal 3 months after nephrectomy (105 +/- 2 mm Hg). Pressure-diameter relations were determined under conditions of maximum active and passive smooth muscle activation. Contiguous segments were used for the determination of water and connective tissue content. Hypertension was associated with increased passive arterial wall stiffness at most sites, with a partial return toward normal after nephrectomy. Maximum responses to smooth muscle activation (active stress and constriction response) were augmented in arteries from hypertensive dogs and partially returned toward normal in the nephrectomized hypertensive group. The elastin content of these arteries was unchanged, while collagen content was nonuniformly decreased in renal hypertensive dogs. Small decreases were found in the radius-wall thickness ratio of some arteries. No significant mechanical changes occurred in the saphenous artery. The largest hypertension-related changes were found in the coronary arteries, which also exhibited the smallest recovery toward normal properties after nephrectomy. Considerable regional variability of changes in arterial wall in renal hypertensive and nephrectomized hypertensive dogs was found. Incomplete resolution of the hypertension and arterial wall changes by nephrectomy was found in this animal model.