Acromegalic patients show the presence of hypertrophic remodeling of subcutaneous small resistance arteries

Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.     

Cellular hypertrophy in subcutaneous small arteries of patients with renovascular hypertension

Structural alterations of small arteries in patients with essential hypertension are characterized by inward eutrophic remodeling. However, small arteries in patients with secondary hypertension, as well as in experimental models of hypertension with high circulating renin, are characterized by inward hypertrophic remodeling, which is characterized by smooth muscle cell hypertrophy in animal models. The aim of our study was to determine whether remodeling of subcutaneous small arteries in patients with secondary forms of hypertension is associated with smooth muscle cell hypertrophy and/or alterations in the elastic modulus of the vessel wall. Fifteen patients with renovascular hypertension, 9 with primary aldosteronism, and 13 with essential hypertension and 9 normotensive subjects were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small arteries were dissected, and morphology was determined on a micromyograph. Unbiased estimates of cell volume and number were made in fixed material. From the resting tension-internal circumference relation of the small arteries, the incremental elastic modulus was calculated and plotted as a function of wall stress. Blood pressure was greater in patients with essential hypertension, renovascular hypertension, or primary aldosteronism than in normotensive subjects, but no significant difference was observed among the 3 groups of hypertensive patients. The media/lumen ratio, the medial cross-sectional area, and the smooth muscle cell volume were significantly greater in patients with renovascular hypertension than in normotensive subjects and patients with essential hypertension. No difference in cell number or in the elastic properties was observed among the 4 groups of subjects. In conclusion, our data demonstrate for the first time that a pronounced activation of the renin-angiotensin-aldosterone system is associated with vascular smooth muscle cell hypertrophy in human hypertension in a manner similar to that found in animal models.     

Effects of antihypertensive therapy on hypertensive vascular disease

Hypertension is associated with alterations in the structure, function, and mechanical properties of large and small arteries. Changes in the endothelium, smooth muscle cell, extracellular matrix, and possibly the adventitia, contribute to complications of hypertension. In large arteries, vascular hypertrophy is found, often with increased stiffness of media components. In small arteries, particularly in mild hypertension, rearrangement of smooth muscle cells around a smaller lumen without changes in media volume (eutrophic remodeling) occurs; in more severe hypertension, hypertrophic remodeling with increased vascular stiffness can be found. Vascular remodeling is accompanied by an increase in the extracellular matrix, particularly collagen deposition. Recent studies have demonstrated that vascular remodeling and endothelial dysfunction of small and large vessels may be normalized by treatment with some antihypertensive agents (angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers). Angiotensin converting enzyme inhibitors have now been shown to improve outcomes in hypertensive patients, an effect that may in part be related to the vascular protective effects reviewed here.     

Adaptation of resistance arteries to increases in pressure

During the development of hypertension, hypertrophy of smooth muscle cells and deposition of extracellular matrix thicken the walls of large arteries without reducing the size of the lumen. The small arteries and arterioles remodel inwardly through a eutrophic process of rearrangement of the same smooth muscle cells around a smaller lumen. Pressure, through an increase in circumferential wall stress, can account for both hypertrophy and inward, eutrophic remodeling. The small arteries constrict during an elevation of pressure, thus restoring wall stress toward control levels. The large arteries have little vasoactivity and respond to the increase in wall stress by initiating a growth process. Mechanotransduction of the pressure stimulus to a growth response is being studied in small mesenteric arteries. Raising the pressure from 90 to 140 mmHg initiates a signaling process starting with phosphorylation of Src within 1 minute. This is followed by phosphorylation of Erk 1/2 peaking at 5 minutes and expression of c-fos mRNA within 30 minutes. Gene expression correlates with wall stress and is thus inhibited by a myogenic response. Maintained vasoconstriction in an isolated arteriole results in inward, eutrophic remodeling within 4 days. Thus, the current data support the hypothesis that wall thickness is determined by circumferential wall stress, and lumen size is determined by vascular tone.     

alphaV integrins are necessary for eutrophic inward remodeling of small arteries in hypertension

Human essential hypertension is characterized by eutrophic remodeling of small arteries, with little evidence of hypertrophy. Likewise, vessels of young hypertensive TGR(mRen2)27 animals have undergone similar structural alterations. The role of integrins in resistance arteries of TGR(mRen2)27 during the eutrophic-remodeling process was examined as blood pressure rose. Initially, 8 alpha and 3 beta integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only alphaV was significantly raised. In conjunction, we confirmed elevated integrin alphaV protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. beta1 and beta3, but not beta5 integrin subunits were coprecipitated with integrin alphaV and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of alphaVbeta3 abolished remodeling but enhanced growth, indicating that hypertrophy supervened as a response to hypertension-induced increases in wall stress. We have established that the only upregulated integrin, the alphaV subunit of integrin alphaVbeta3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific alphaVbeta3-extracellular matrix interactions are likely to allow vascular smooth muscle cell-length autoregulation, which includes a migratory process, to maintain a narrowed lumen after a prolonged constricted state.     

Activation of resistance arteries with endothelin-1: from vasoconstriction to functional adaptation and remodeling

Remodeling of resistance arteries is a key feature in hypertension. We studied the transition of vasoconstriction to remodeling in isolated rat skeletal muscle arterioles. Arterioles activated with 10 nM endothelin-1 showed functional adaptation when kept at low distension in a wire myograph setup, where contractile properties shifted towards a smaller lumen diameter after 1 day. Pressurized arteries kept in organoid culture showed physical inward remodeling after 3-day activation with 10 nM endothelin-1, characterized by a reduction in relaxed diameter without a change in the wall cross-sectional area (eutrophic remodeling). The relaxed lumen diameter (at 60 mm Hg) decreased from 169 +/- 5 (day 0) to 155 +/- 4 microm (day 3). An antibody directed to the beta(3)-integrin subunit (but not one directed to the beta(1)-integrin subunit) enhanced remodeling, from a reduction in relaxed diameter at 60 mm Hg of 15 +/- 2.4 to 22 +/- 1.8 microm (both on day 3). Collagen gel contraction experiments showed that the antibody directed to the beta(3)-integrin subunit enhanced the compaction of collagen by smooth muscle cells, from 83 +/- 1.5 to 68 +/- 1.5% of the initial gel diameter. In conclusion, these data show that inward eutrophic remodeling is a response to sustained contraction, which may involve collagen reorganization through beta(3)-integrins.     

Impairment of hypoxic pulmonary artery remodeling by heparin in mice

Chronic hypoxia produces pulmonary artery hypertension and remodeling of pulmonary arteries with hypertrophy of smooth muscle in the media and extension of smooth muscle into more distal small precapillary arteries. The present study investigated the influence of heparin, an inhibitor of platelet-derived growth factor, and of the clotting cascade on this remodeling. Mice maintained in room air or 10% O2 for 26 days were treated with low-dose heparin at 75 units/kg or high dose heparin at 300 units/kg. Pulmonary hypertension and right ventricular hypertrophy developed in the hypoxic mice compared with the room air mice as evidenced by the greater (p less than 0.05) right ventricular systolic pressure (36 +/- 4 SEM versus 21 +/- 1 mmHg) and the increase (p less than 0.05) in right heart weight/left ventricular plus septal weight (35 +/- 1.6 SEM versus 25.2 +/- 1.3). Hypoxia also induced smooth muscle hypertrophy in small pulmonary arteries, with an increase (p less than 0.05) in the percent media thickness/vascular diameter from 5.7 +/- 1 SEM to 13.3 +/- 3 and an apparent decrease (p less than 0.05) in distal small pulmonary arteries from 4.4 +/- 0.2 SEM to 2.05 +/- 0.1 per 100 alveoli. High-dose heparin partially but significantly (p less than 0.05) prevented the pulmonary artery hypertension (right ventricular systolic pressure of 28 +/- 2 mmHg), the right ventricular hypertrophy (right ventricular weight/left ventricular plus septal weight of 30.1 +/- 1) and remodeling of distal small pulmonary arteries (media thickness/vascular diameter of 8.4 +/- 1%, small pulmonary artery/100 alveoli of 3.63 +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

实验性高血压所致的颅内大动脉损害

为观察实验性高血压所致的颅内大动脉损害的特征．将易卒中型肾血管性高血压大鼠的大脑中动脉和基底动脉进行形态学测量．并观察了用卡托普利抗高血压治疗后这些测量参数的变化。结果发现，高血压大鼠的大脑中动脉和基底动脉均有中层肥厚，但前者主要由平滑肌细胞增殖、肥大引起，后者却主要是血管壁重构的结果。卡托普利抗高血压治疗可控制平滑肌细胞增殖、肥大，但不能改善血管壁重构。以上结果提示，高血压所致的颅内动脉损害主要表现为血管中层肥厚，而且不同血管对高血压和抗高血压治疗的反应有差异。     

Endothelial dysfunction in small resistance arteries of patients with non-insulin-dependent diabetes mellitus

OBJECTIVE: Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM+EH). PATIENTS AND METHODS: All subjects were submitted to a biopsy of the subcutaneous fat Small arteries were dissected and mounted on a micromyograph. The media to lumen ratio (M/L) was calculated. A concentration-response curve to acetylcholine, to bradykinin as well as to the endothelium-independent vasodilator sodium nitroprusside were performed. We also evaluated the contractile response to endothelin-1. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) plasma levels were also measured. RESULTS: The vasodilatation to acetylcholine and bradykinin (but not to sodium nitroprusside) was significantly and similarly reduced in EH, in NIDDM, and in NIDDM+EH compared with NT. The contractile response to endothelin-1 was similarly reduced in EH, in NIDDM and in NIDDM+EH. Plasma ICAM-1 and VCAM-1 concentrations were higher in EH, NIDDM and NIDDM+EH than in NT. CONCLUSIONS: An evident endothelial dysfunction was detected in patients with NIDDM, and the simultaneous presence of EH did not seem to exert an additive effect. The contractile responses to endothelin-1 were reduced possibly as a consequence of ET(A) receptor down-regulation.     

Vascular but not cardiac remodeling is associated with superoxide production in angiotensin II hypertension

OBJECTIVE: Angiotensin (Ang) II increases reactive oxygen species (ROS), decreases nitric oxide (NO) bioavailability and promotes cardiovascular remodeling. ROS have been identified as critical second messengers of the trophic responses by Ang II. In rats with Ang II-induced hypertension, we investigated the role of ROS in cardiac hypertrophy as well as the remodeling of aortas and mesenteric (resistance) arteries. METHODS: Sprague-Dawley rats received Ang II (0.7 mg/kg per day by mini-pump, n = 7) or vehicle (n = 7) for 5 days. Endothelium-dependent relaxation to acetylcholine (EDR) in aortas was determined in organ baths and in mesenteric resistance vessels in a pressurized myograph. Superoxide (O2) production was measured by lucigenin chemiluminescence, laser-confocal fluorescence microscopy (LCM) and NADPH oxidase assay. RESULTS: Ang II-treated rats developed hypertension (183 +/- 3 versus 138 +/- 4 mmHg, P < 0.05), increased aortic O2 (50%), aortic hypertrophy (12%) and impaired EDR. Mesenteric arteries manifested impaired EDR, increased NADPH oxidase activity (356%) and eutrophic inward remodeling (decreased lumen diameter and increased wall/lumen ratio). However, although Ang II-treated rats developed cardiac hypertrophy (13%), this was not accompanied by an increase in cardiac O2, as measured by lucigenin, LCM or NADPH oxidase assay. On the other hand, cardiac calcineurin, a molecule that promotes cardiac hypertrophy linked to Ang II, was increased by 40% (52 +/- 8 versus 33 +/- 5 pmol/min per mg protein, P < 0.05). CONCLUSION: These studies demonstrate that the role of ROS in Ang II-induced vascular remodeling differ across vascular territories. Although in conduit and resistance vessels, vascular hypertrophy and endothelial dysfunction are linked to increased ROS production, cardiac hypertrophy is not. Instead, cardiac hypertrophy is associated, at least in part, with an increase in calcineurin. These studies unveil novel mechanisms that may play an important role in the pathogenesis of cardiac and vascular injury in hypertension.     

Cardiovascular hypertrophy in one-kidney, one-clip renal hypertension is resistant to heparin

OBJECTIVE: Heparin inhibits vascular hypertrophy in angiotensin-induced hypertension, in addition to its well-known role in inhibiting injury-induced vascular smooth muscle proliferation. We tested whether hypertension and vascular hypertrophy could be reduced by heparin independently from the renin-angiotensin system. METHODS: Rats were made hypertensive with a one-kidney, one-clip (1K1C) procedure and received heparin from osmotic minipumps (0.3 mg/h per kg i.v.) or saline vehicle for 2 weeks. Blood pressure was measured by the tail-cuff method and vessel cross-sectional area was measured by morphometry in the aorta and mesenteric arteries. Proliferation was assessed with bromodeoxyuridine labelling. RESULTS: Blood pressure elevation and cardiovascular hypertrophy were evident in 1K1C rats. The media of mesenteric arteries was increased by 25%, and the media : lumen ratio by 35%, in hypertensive rats. DNA synthesis by smooth muscle cells in the mesenteric arteries was increased sevenfold in renal hypertension. Heparin treatment did not influence either the increase in blood pressure, the cardiovascular hypertrophy response or hypertension-mediated proliferation of arterial smooth muscle cells. CONCLUSIONS: These data suggest that the vascular hypertrophy mechanisms operating in 1K1C renal hypertension are not inhibited by heparin and thus are different from those in angiotensin-mediated hypertension. Identifying such mechanisms in the future will be important for devising appropriate intervention strategies in angiotensin-independent forms of vascular hypertrophy.     

Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP

BACKGROUND AND AIM: Increased vascular resistance is a hallmark of hypertension and involves structural alterations, which may entail smooth muscle cell hypertrophy or hyperplasia, or qualitative or quantitative changes in extracellular matrix (ECM) proteins. Since the renin-angiotensin-aldosterone system modulates these changes, we investigated the effects of 8 weeks of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril (RAM), or a dual ACE and neutral endopeptidase (NEP) inhibitor, MDL-100240 (MDL), on mesenteric small artery structure and ECM proteins in mRen2-transgenic rats (TGRs), an animal model of hypertension with severe cardiovascular damage. MATERIALS AND METHODS: Thirty-five 5-week-old rats were included in the study: six TGRs received RAM; five TGRs RAM + the bradykinin receptor inhibitor, icatibant; six TGRs, MDL; and five TGRs MDL + icatibant, while eight TGRs and five normotensive Sprague-Dawley controls were kept untreated. Mesenteric small arteries were dissected and mounted on a micromyograph. The media-to-lumen ratio (M/L) was then calculated. Vascular metalloproteinase (MMP) content was evaluated by zymography. RESULTS: In untreated TGRs severe hypertension was associated with inward eutrophic remodelling of small arteries. Both RAM and MDL prevented the increase in blood pressure and M/L and decreased MMPs. Icatibant blunted the effect of MDL on BP, M/L and MMPs. CONCLUSIONS: Changes in collagenase activity induced by ramipril and MDL are associated with prevention of small artery structural alterations in TGRs. Furthermore, MDL-induced enhancement of bradykinin could play a role in both the prevention of vascular structural alterations and in the stimulation of MMPs.     

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.     

Small artery remodeling depends on tissue-type transglutaminase

Remodeling of small arteries is essential in the long-term regulation of blood pressure and blood flow to specific organs or tissues. A large part of the change in vessel diameter may occur through non-growth-related reorganization of vessel wall components. The hypothesis was tested that tissue-type transglutaminase (tTG), a cross-linking enzyme, contributes to the inward remodeling of small arteries. The in vivo inward remodeling of rat mesenteric arteries, induced by low blood flow, was attenuated by inhibition of tTG. Rat skeletal muscle arteries expressed tTG, as identified by Western blot and immunostaining. In vitro, activation of these arteries with endothelin-1 resulted in inward remodeling, which was blocked by tTG inhibitors. Small arteries obtained from rats and pigs both showed inward remodeling after exposure to exogenous transglutaminase, which was inhibited by addition of a nitric oxide donor. Enhanced expression of tTG, induced by retinoic acid, increased inward remodeling of porcine coronary arteries kept in organ culture for 3 days. The activity of tTG was dependent on pressure. Inhibition of tTG reversed remodeling, causing a substantial increase in vessel diameter. In a collagen gel contraction assay, tTG determined the compaction of collagen by smooth muscle cells. Collectively, these data show that small artery remodeling associated with chronic vasoconstriction depends on tissue-type transglutaminase. This mechanism may reveal a novel therapeutic target for pathologies associated with inward remodeling of the resistance arteries.     

Effects of insulin on endothelial and contractile function of subcutaneous small resistance arteries of hypertensive and diabetic patients

The effect of insulin on the vasoconstriction induced by norepinephrine is at present controversial. We have previously demonstrated that high-concentration insulin may induce an increased reactivity to norepinephrine in mesenteric small resistance arteries of spontaneously hypertensive rats. The aim of the present study was to evaluate the effects of low- and high-concentration insulin on the concentration-response curves to norepinephrine and acetylcholine in subcutaneous small resistance arteries of hypertensive and diabetic patients. Twelve normotensive subjects (NT), 11 patients with essential hypertension (EH), 8 patients with non-insulin-dependent diabetes mellitus (NIDDM), and 8 patients with both EH and NIDDM (EH + NIDDM) were included in the study. Subcutaneous small resistance arteries were dissected and mounted on an isometric myograph. Concentration-response curves to norepinephrine (from 10(-8) to 10(-5) mol/l) and acetylcholine (from 10(-9) to 10(-5) mol/l) were performed in the presence or absence of insulin 715 pmol/l (low concentration) and 715 nmol/l (high concentration). A significant reduction in the contractile response to norepinephrine was observed in NT after preincubation of the vessels with both low- and high-concentration insulin. No reduction was observed in NIDDM and EH + NIDDM, while a significant decrease was obtained in EH with high-concentration insulin. Moreover, a significant difference in reduction in contractile response at maximal concentration of norepinephrine in the presence of low-concentration insulin was observed in NT compared to EH (p = 0.03), NIDDM (p = 0.02), and EH + NIDDM (p = 0.05), whereas no difference was observed with high-concentration insulin. No differences in the concentration-response curves to acetylcholine before or after precontraction with either low- or high-concentration insulin were observed in any group. In conclusion, insulin at low (physiological) concentrations seems to induce a decreased reactivity to norepinephrine in subcutaneous small resistance arteries of NT, but this effect was lost in EH, NIDDM and EH + NIDDM. This effect does not seem to involve acetylcholine-stimulated nitric oxide release.     

Morphometric study of mesenteric arteries from genetically hypertensive Dahl strain rats

Morphometric measurements on different arteries at the light-microscopic level and ultrastructural studies of the mesenteric arteries were carried out in salt-sensitive (DS) and salt-resistant (DR) Dahl rats given a high-salt (8%) or low-salt (0.4%) diet for 6-7 weeks. Hypertension was produced in DS rats given high-salt diet (DS-H), while only moderate hypertension was produced in DS rats given low-salt diet (DS-L). Blood pressure in DR rats given high salt (DR-H) and low salt (DR-L), however, was normal. Cross-sectional area of the media was increased significantly in the superior mesenteric artery (an elastic artery), large mesenteric arteries (muscular arteries) and small mesenteric arteries (small muscular arteries or arterioles) from DS-H rats. In all the vessel types, this increase was positively correlated with the increase in blood pressure. In the superior mesenteric artery, medial wall increase was probably due to an increase in intercellular space, and/or hypertrophy of the smooth muscle cells. Similarly, increase in the media of small mesenteric arteries was probably due to hypertrophy of the smooth muscle cells. In contrast, increase in the media of large mesenteric arteries was related to hyperplasia of the smooth muscle cells. Damage to endothelial cells was noted in the 3 vessel types from DS-H. Intimal lesions composed of myointimal cells were found in the superior mesenteric arteries of all the rat groups. Our results showed that the incidence of these lesion formations was higher in the following order: DS-H greater than DS-L greater than DR-H greater than DR-L, suggesting that the degree of hypertension (DS vs. DR rats) and the amount of salt in the diet (DR-H vs. DR-L) may be some of the factors contributing to the development of these lesions. We conclude that hyperreactivity of the arteries due to increase in medial smooth muscle mass (e.g. muscular arteries), and/or probably impaired relaxation capability of the arteries in the DS-H rats due to endothelial cell damage, may contribute to the elevation of BP in the Dahl model of genetic hypertension.     

Cellular hypertrophy in mesenteric resistance vessels from renal hypertensive rats

To determine whether the increased thickness seen in media of mesenteric resistance vessels of Wistar-Kyoto rats made hypertensive by a Goldblatt procedure (one-kidney, one clip model) was due to hypertrophy or hyperplasia of smooth muscle cells, the cellular dimensions of these vessels were estimated using a new, unbiased stereological method (the disector). Furthermore, to investigate whether the changes seen could be secondary to the increased blood pressure, morphometric measurements were also made in renal arcuate arteries, which, due to the constricting silver clip, probably had not been exposed to the increased pressure load. Vessels were mounted on a myograph, and their media thickness, lumen diameter, and maximum active wall tension response were measured. In the mesenteric vessels media thickness had increased by 58%, whereas no changes were seen in the renal vessels. Vessels were then fixed, and serial sections were made in the mesenteric vessels. The disector was used to calculate the numerical cell density in each vessel. By combining the myograph measurements and the estimated numerical cell density, the number of cells per segment unit length was calculated (renal hypertensive rats, 6.8 micron-1; sham-operated Wistar-Kyoto rats, 6.3 micron-1; p greater than 0.40) and mean cell volume was determined (renal hypertensive rats, 1541 micron 3; sham-operated Wistar-Kyoto rats, 1256 micron 3; p less than 0.02). No morphometrical changes were found in single sections of the renal arteries. We conclude that the increased media thickness observed in mesenteric resistance vessels of one-kidney, one clip Goldblatt hypertensive rats mainly was caused by smooth muscle cell hypertrophy.     

自发性高血压大鼠高血压前期及高血压期脑动脉的形态计量学研究

用半自动图像分析仪对7周和17周龄自发性高血压大鼠的脑动脉进行形态计量学研究,并与Wistar-Kyoto大鼠对照。结果表明,自发性高血压大鼠在高血压前期及高血压期脑动脉中膜与对照组比较均明显增厚;细动脉中膜增厚是因平滑肌细胞肥大所致。自发性高血压大鼠在高血压前期已有动脉中膜肥厚,提示这种血管壁结构变异对高血压的发生发展有重要意义。     

实验性高血压所致的基底动脉结构改变及血管紧张素转换酶抑制剂的影响

探讨高血压大鼠基底动脉结构的变化及血管紧张素转换酶抑制剂对其的影响。选用易卒中型肾血管性高血压大鼠模型 ,分为高血压组、卡托普利治疗组、假手术正常血压对照组。分别于肾动脉狭窄术后 4、8、12周处死动物 ,取基底动脉 ,制片后分别用光镜和透射电镜观察 ,并进行体视学定量分析。术后 4周时高血压组基底动脉光镜下无明显形态学变化 ,8周和 12周时中膜厚度、壁腔比值均比同时期正常血压对照组增加 ,有显著性差异 (P <0 .0 5 ) ;卡托普利治疗后中膜厚度、壁腔比值均小于高血压组 ,差异有显著性 (P <0 .0 5 )。术后 4周高血压组基底动脉平滑肌细胞间隙略增宽 ;术后 8周细胞器肿胀 ,部分溶解 ,间质轻度水肿 ;12周时平滑肌细胞肌丝变性、断裂、溶解 ,内质网扩张 ,线粒体部分空泡变性 ,细胞坏死。卡托普利组各时期超微结构改变不明显。表明高血压可致基底动脉肥厚和超微结构破坏 ,而卡托普利可以预防高血压所致的基底动脉结构破坏。