Structural abnormalities of small resistance arteries in essential hypertension

Regardless of the mechanisms that initiate the increase in blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, the small arteries smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, while in some secondary forms of hypertension, a hypertrophic remodeling may be detected. Also, in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling of subcutaneous small arteries is present. The results from our own group have suggested that indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Therefore, the regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure, both in human and in animal models of genetic and experimental hypertension. A complete normalization of small resistance artery structure is demonstrated in hypertensive patients, after long-term and effective therapy with ACE inhibitors, angiotensin II receptor blockers and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin–angiotensin system seems to be effective in this regard. In conclusion, there are several pieces of evidence that suggest that small resistance artery structure may be considered an intermediate endpoint in the evaluation of the effects of antihypertensive therapy; however, there are presently no data available about the prognostic impact of the regression of vascular structural alterations in hypertension and diabetes.     

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.     

Correlation of endothelial function in large and small arteries in human essential hypertension

OBJECTIVES: The structure and function of blood vessels varies along the vascular tree, and alterations found in hypertension are also different. The aim of this study was to determine whether non-invasive measurement of endothelial function in conduit arteries reflects that of subcutaneous resistance arteries measured in vitro. METHODS AND RESULTS: Sixteen essential hypertensive patients (aged 50 +/- 2 years) were studied. Flow-mediated dilation (FMD) during reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG)-induced dilatation (endothelium-independent) were assessed in brachial arteries by ultrasound. Structure, and acetylcholine (10(-9) to 10(-4) mol/l) and sodium nitroprusside (SNP, 10(-8) to 10(-3) mol/l)-induced vasorelaxation of resistance arteries dissected from gluteal subcutaneous biopsies were measured in vitro using a pressurized myograph. Brachial artery FMD and NTG-induced dilatation were 8.4 +/- 1.0 and 18.1 +/- 1.4%, respectively. Resistance arteries of hypertensive patients showed greater media:lumen ratio (8.6 +/- 0.4 versus 5.9 +/- 0.3% in normotensive subjects, P< 0.01), and maximal acetylcholine responses was diminished to 75 +/- 6% compared to normotensive subjects (97 +/- 2%, P< 0.01). FMD correlated with maximal acetylcholine responses (r2 = 0.57, P< 0.001). FMD did not correlate significantly with the media: lumen ratio of resistance arteries (r2 = -0.22, P= 0.07). By multivariate analysis, FMD predicted resistance artery endothelial function independently of age, sex, body mass index, blood lipid status and lumen diameter of brachial artery (beta = 0.81, P< 0.001). CONCLUSIONS: Endothelial dilatory responses are similar in large and small arteries in hypertensive patients. Abnormal FMD in the brachial artery predicts the presence of endothelial dysfunction in human resistance arteries, suggesting that impairment of endothelial function is a generalized alteration in hypertension. Ultrasound measurement of endothelial dysfunction in the brachial artery appears to be less sensitive than in-vitro measurement in resistance arteries.     

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.     

Remodeling of coronary arteries in diabetic patients-an intravascular ultrasound study

BACKGROUND: Coronary artery remodeling is a structural change in the vessel wall and typically in response to atherosclerotic plaque. The nature of coronary remodeling has been described in different clinical situations. However, remodeling characteristics of coronary arteries of diabetic patients have never been studied. HYPOTHESIS: We tested the hypothesis that positive remodeling of coronary artery in response to atherosclerotic plaque in diabetic patients would be less compared to nondiabetic patients. METHODS: Coronary intravascular ultrasound analysis of data in 26 consecutive patients (12 diabetic and 14 nondiabetic) was performed. Linear regression analyses of vessel area versus plaque area were carried out to establish a relation between the degree of plaque and the extent of remodeling in diabetic and nondiabetic groups. RESULTS: The positive remodeling quantified as the slope of the regression line was similar in both the groups (diabetic group 1.32 and nondiabetic group 0.80) when all segments with different plaque areas were considered (P > 0.05). However, the diabetic group had greater positive remodeling in segments with plaque area less than 55%, as the slope for diabetic group was 2.01 and nondiabetic group was 1.40 (P < 0.05). CONCLUSIONS: Both the diabetic and nondiabetic patients had positive remodeling in response to atherosclerotic plaque formation. Diabetics had greater positive remodeling in the early stages of atherosclerosis compared to nondiabetics, thus providing evidence against our hypothesis. The adverse clinical outcomes in diabetics may not be due to inadequate positive remodeling of coronary arteries as previously thought.     

Stenting small coronary arteries

Stenting of small coronary arteries was long contra-indicated because of a high rate of subacute occlusion. We report a single-center registry including 190 patients stented with 2.5 mm balloons. Procedural success was 98% and subacute occlusion rate was 2.6%. Clinical follow-up showed a 24.5% repeat intervention rate. These results seemed acceptable, warranting stent implantation in small arteries in the case of acute or threatened closure. New stent designs and coatings may contribute to the improvement of outcomes and to the decrease in subacute occlusion and restenosis rates.     

Structural changes in small resistance arteries and left ventricular geometry in patients with primary and secondary hypertension

OBJECTIVE : To prospectively evaluate the interrelationships between left ventricular (LV) geometry and structural characteristics of the vessel wall in small resistance arteries in patients with consecutive primary and secondary hypertension. METHODS : In 14 patients with phaeochromocytoma, 12 with primary aldosteronism, 25 with renovascular, 25 with essential hypertension and 12 normotensive controls, an echocardiographic study for the measurement of LV mass index and relative wall thickness (RWT) was performed. Morphological characteristics of small resistance arteries (relaxed diameter < 300 microm) were directly evaluated by a micromyographic technique. RESULTS : A total of 25 patients had normal LV mass and geometry, 28 patients had normal RWT (< 0.45) and 23 patients had a RWT >or= 0.45; all normotensive subjects had normal LV mass and geometry. Media to lumen ratio (M/L) in subcutaneous small arteries was greater in hypertensive patients with concentric LV hypertrophy in respect to normotensives (ANOVA P = 0.01) and hypertensives with normal LV geometry (ANOVA P = 0.05). In the whole group of hypertensive patients the correlation coefficient between M/L and LV mass index was 0.33 (P < 0.05); the correlation coefficient between M/L and RWT was 0.46 (P < 0.01) and it was higher in primary aldosteronism (r = 0.67) and renovascular hypertension patients (r = 0.46). CONCLUSIONS : A close relation between morphology of subcutaneous small resistance arteries and LV geometric patterns may be observed in hypertensive patients; this relationship is more evident when the renin-angiotensin-aldosterone system is activated.     

冠状动脉小血管支架植入的临床研究

目的：观察冠状动脉小血管病变患者的临床特点、支架植入情况及预后效果。方法：回顾分析冠状动脉小血管严重狭窄患者的临床及支架植入资料，并与同期进行的冠脉大血管支架患者进行比较，比较二者的临床特点、手术方法及预后的异同。结果：冠脉小血管支架组植入成功率97．14％，大血管支架组植入成功率98．95％（P〉0．05）；两组在年龄、性别及高血压患病率方面组间比较差异无统计学意义（P〉0．05），2型糖尿病患病率在小血管支架组高于大血管支架组（P〈0．05）；植入方法上，使用球囊预扩的比例两组比较差异无统计学意义（P〉0．05）；支架释放后球囊后扩张比例小血管支架组低于大血管支架组（P〈0．05）；术中并发症及随访期预后差异元统计学意义（P〉0．05）。结论：冠状动脉小血管支架植入的成功率、预后与大血管支架组无显著差异，可安全地用于冠脉小血管病变的治疗。     

Endothelium-dependent hyperpolarization in small gastric arteries

OBJECTIVE: In many blood vessels, stimulation of the endothelium with various vasoactive substances induces, besides the nitric oxide (NO) and prostacyclin pathways, a third mechanism evoking dilatation. It is based on hyperpolarization of the vascular smooth muscle cell membrane. In the present study, we investigated the existence of endothelium-dependent hyperpolarization in small gastric arteries of the rat and explored its underlying mechanism. METHODS: Membrane potentials were recorded by conventional microelectrode techniques in isolated segments of small gastric arteries, the normalized diameter of which was determined from the passive wall tension-internal circumference characteristics as measured with a myograph. RESULTS: After blocking NO and prostaglandin synthesis, application of acetylcholine (3 x 10(-7) M) resulted in a membrane hyperpolarization in endothelium intact but not in endothelium-denuded arteries. This membrane potential change was increased by pre-exposure to a low concentration (30 microM) of Ba2+, which selectively inhibits inward rectifying potassium channels. Moreover, the acetylcholine-induced hyperpolarization was unaffected by additional pre-exposure to high concentrations (0.5 mM) of the Na/K-ATPase inhibitor ouabain, which by itself caused a secondary slow endothelium-independent hyperpolarization after an initial peak depolarization. CONCLUSIONS: We conclude that acetylcholine produces endothelium-dependent hyperpolarization in gastric small arteries, which does not rely on activation of smooth muscle cell inward rectifying K+ channels or Na/K pumps, and might prove to be another important regulator of gastric mucosal blood flow.     

Effectiveness of stents in small coronary arteries

This study was prospectively randomized to assess the efficacy and safety of Jo heparin-coated stent deployment in small vessels compared with balloon angioplasty. In 202 patients, restenosis in balloon and stent arms was 49% and 30%, respectively.