Manifestaciones pulmonares y sistémicas de la hipertensión arterial pulmonar: Un enfoque panvascular

La hipertensión arterial pulmonar (HAP) es una grave enfermedad cuyo resultado final de la interacción entre el tono vascular y la alteración progresiva de la remodelación de las arterias pulmonares provoca insuficiencia cardíaca derecha y muerte. El remodelado vascular pulmonar es la alteración estructural clave en la hipertensión pulmonar. Este proceso implica cambios en la íntima, media, adventicia y espacio perivascular, a menudo con la interacción de células inflamatorias. Los mecanismos fisiopatológicos de la HAP abarcan una serie de modificaciones vasculares que producen un aumento de la resistencia vascular pulmonar. Las modificaciones vasculares que se producen en la HAP incluyen: la vasoconstricción, la proliferación del músculo liso, la inflamación, la apoptosis endotelial, la proliferación endotelial resistente a la apoptosis, la fibrosis, la trombosis in-situ, y finalmente, las lesiones plexiformes. Hasta hace poco, la HAP se consideraba una enfermedad restringida a la circulación pulmonar. Sin embargo, existe una creciente evidencia de que los pacientes con HAP también exhiben disfunción vascular sistémica, como lo demuestra la alteración de la dilatación mediada por el flujo de la arteria braquial, el flujo sanguíneo cerebral anormal, la miopatía esquelética y la enfermedad renal intrínseca. Los datos recientes apoyan un vínculo con los eventos genéticos y moleculares detrás de la patogénesis de la HAP. Esta revisión sirve de introducción a los principales hallazgos sistémicos en la HAP y la evidencia que apoya un vínculo común con la fisiopatología de la HAP. Sobre la base de la evidencia disponible, proponemos un paradigma en el que las anomalías metabólicas, la lesión genética y la disfunción vascular sistémica contribuyen a las manifestaciones sistémicas de la HAP. Este concepto no sólo abre interesantes posibilidades de investigación, sino que también anima a considerar las manifestaciones extrapulmonares en el tratamiento de los pacientes con HAP, pues la disfunción vascular sistémica contribuiría a las manifestaciones sistémicas de la HAP.

Pulmonary arterial hypertension (PAH) is a serious disease whose end result of the interaction between vascular tone and the progressive alteration of the remodeling of the pulmonary arteries causes right heart failure and death. Pulmonary vascular remodeling is the key structural alteration in pulmonary hypertension. This process involves changes in the intima, media, adventitia, and perivascular space, often with the interaction of inflammatory cells. The pathophysiological mechanisms of PAH include a series of vascular modifications that produce an increase in pulmonary vascular resistance. Vascular modifications that occur in PAH include: vasoconstriction, proliferation of smooth muscle, inflammation, Endothelial apoptosis, apoptosis-resistant endothelial proliferation, fibrosis, in-situ thrombosis, and finally, plexiform lesions. Until recently, PAH was considered a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Recent data support a link to the genetic and molecular events behind the pathogenesis of PAH. This review serves as an introduction to the main systemic findings in PAH and the evidence supporting a common link with the pathophysiology of PAH. Based on the available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to the systemic manifestations of PAH. This concept not only opens up interesting research possibilities, but also encourages consideration of extrapulmonary manifestations in the treatment of patients with PAH, since systemic vascular dysfunction would contribute to the systemic manifestations of PAH.

A hipertensão arterial pulmonar (HAP) é uma doença grave cujo resultado final da interação entre o tônus vascular e a alteração progressiva da remodelação das artérias pulmonares causa insuficiência cardíaca direita e morte. A remodelação vascular pulmonar é a principal alteração estrutural na hipertensão pulmonar. Esse processo envolve mudanças na íntima, média, adventícia e espaço perivascular, muitas vezes com a interação de células inflamatórias. Os mecanismos fisiopatológicos da HAP incluem uma série de modificações vasculares que produzem um aumento na resistência vascular pulmonar. As modificações vasculares que ocorrem na HAP incluem: vasoconstrição, proliferação do músculo liso, inflamação, apoptose endotelial, proliferação endotelial resistente à apoptose, fibrose, trombose in situ e, finalmente, lesões plexiformes. Até recentemente, a HAP era considerada uma doença restrita à circulação pulmonar. No entanto, há evidências crescentes de que os pacientes com HAP também apresentam disfunção vascular sistêmica, conforme evidenciado pela dilatação prejudicada mediada pelo fluxo da artéria braquial, fluxo sanguíneo cerebral anormal, miopatia esquelética e doença renal intrínseca. Dados recentes suportam uma ligação com os eventos genéticos e moleculares por trás da patogênese da HAP. Esta revisão serve como uma introdução aos principais achados sistêmicos em HAP e as evidências que apoiam uma ligação comum com a fisiopatologia da HAP. Com base nas evidências disponíveis, propomos um paradigma em que anormalidades metabólicas, lesão genética e disfunção vascular sistêmica contribuem para as manifestações sistêmicas da HAP. Esse conceito não apenas abre possibilidades interessantes de pesquisa, mas também incentiva a consideração das manifestações extrapulmonares no tratamento de pacientes com HAP, uma vez que a disfunção vascular sistêmica contribuiria para as manifestações sistêmicas da HAP.

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

OBJECTIVE: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. MATERIALS AND METHODS: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated. RESULTS: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. CONCLUSION: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii / 神经科学通报·英文版

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.

The manufacture and application of novel evaluating tool for renal vascular anatomy: the system of individualized reno-vasculature evaluation for nephrectomy / 中华泌尿外科杂志

Objective@#To explore the clinical feasibility and effectiveness of novel preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy for retroperitoneoscopic radical nephrectomy (RLRN).@*Methods@#Two-hundred and fifty one consecutive patients who underwent RLRN for renal tumours from September 2016 to March 2018 were enrolled prospectively, including 154 males (61.4%) and 97 females (38.6%), aged 26 to 84 years with the mean age of 58.7 and mean BMI of 25.8 kg/m2. The tumors were all isolated with the mean size of 5.4 cm. According to presence or absence of vascular correlation events (VCE) and nephrectomy times under endoscope (NTE), all the cases were divided into two groups: the common group (VCE, NTE <60 min) and the difficult group (no VCE, NTE ≥60 min). With the help of preoperative three-dimensional reconstruction, the specific and crucial arteriovenous anatomical features were recorded, which consist of side, count, spatial configuration and density of the vessel to be processed. After univariable analysis, multivariable analysis with logistic regression was performed for the selected risk factors. Individualized reno-vasculature evaluation for nephrectomy were established, when the value of risk factors were assigned separately according to its correlation and clinical practice.@*Results@#There was no statistical significance between common group and difficult group in the aspects of gender, age, BMI, maximum diameter of the tumor, R. E.N.A.L. score and PADUA score. There were statistical significance between common group and difficult group in the aspects of N (number of total vessels), D (vascular anomalies density), C (3D conformation), S (sides) of pending renal vessels (χ2=125.700, 102.014, 97.090, 12.603, P<0.05). The correlation of N, D, C were closely related (standardized regression coefficient were 0.742, 0.664, 0.324, P<0.05), but S was not significant (P>0.05). SIREN was preliminarily established as a preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy. Of the 5 components of SIREN, N, D were scored on 1 to 3 points, C was scored on 0 to 3 points, E was scored on 0 to 1 point, and S was not scored but showed in terms of L or R. All of these constitute the assessment content with a full score of 10 points except S suffixed by L or R instead of scores. There was a statistically significant difference during low (2-3 points), middle (4-6 points), and high (7-10 points) groups (χ2=126.927, P<0.05) according to the comparisons between low and middle, low and high, as well as middle and high (χ2=90.997, 7.195, 91.679, P<0.05).@*Conclusions@#In virtue of the renal vascular scoring system named after SIREN by 3d reconstructing, the spatial structure information of the renal vascular system can be obtained accurately and expressed directly before operation, the difficulty of vascular treatment can be predicted, the preoperative planning can be optimized, and the accurate quantitative evaluation of renal vascular anatomical structure can be achieved to further improve the surgical safety and efficiency.

The manufacture and application of novel evaluating tool for renal vascular anatomy : the system of individualized reno-vasculature evaluation for nephrectomy / 中华泌尿外科杂志

Objective To explore the clinical feasibility and effectiveness of novel preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy for retroperitoneoscopic radical nephrectomy (RLRN).Methods Two-hundred and fifty one consecutive patients who underwent RLRN for renal tumours from September 2016 to March 2018 were enrolled prospectively,including 154 males (61.4％) and 97 females (38.6％),aged 26 to 84 years with the mean age of 58.7 and mean BMI of 25.8 kg/m2.The tumors were all isolated with the mean size of 5.4 cm.According to presence or absence of vascular correlation events (VCE) and nephrectomy times under endoscope (NTE),all the cases were divided into two groups:the common group (VCE,NTE ＜ 60 min)and the difficult group (no VCE,NTE ≥ 60 min).With the help of preoperative three-dimensional reconstruction,the specific and crucial arteriovenous anatomical features were recorded,which consist of side,count,spatial configuration and density of the vessel to be processed.After univariable analysis,muhivariable analysis with logistic regression was performed for the selected risk factors.Individualized renovasculature evaluation for nephrectomy were established,when the value of risk factors were assigned separately according to its correlation and clinical practice.Results There was no statistical significance between common group and difficult group in the aspects of gender,age,BMI,maximum diameter of the tumor,R.E.N.A.L.score and PADUA score.There were statistical significance between common group and difficult group in the aspects of N (number of total vessels),D (vascular anomalies density),C (3Dconformation),S (sides) of pending renal vessels (x2 =125.700,102.014,97.090,12.603,P ＜0.05).The correlation of N,D,C were closely related (standardized regression coefficient were 0.742,0.664,0.324,P ＜ 0.05),but S was not significant (P ＞ 0.05).SIREN was preliminarily established as a preoperative evaluating tool to achieve accurate and quantitative evaluation of renal vascular anatomy.Of the 5 components of SIREN,N,D were scored on 1 to 3 points,C was scored on 0 to 3 points,E was scored on 0 to 1 point,and S was not scored but showed in terms of L or R.All of these constitute the assessment content with a full score of 10 points except S suffixed by L or R instead of scores.There was a statistically significant difference during low (2-3 points),middle (4-6 points),and high (7-10 points) groups (x2 =126.927,P ＜ 0.05) according to the comparisons between low and middle,low and high,as well as middle and high (x2 =90.997,7.195,91.679,P ＜ 0.05).Conclusions In virtue of the renal vascular scoring system named after SIREN by 3d reconstructing,the spatial structure information of the renal vascular system can be obtained accurately and expressed directly before operation,the difficulty of vascular treatment can be predicted,the preoperative planning can be optimized,and the accurate quantitative evaluation of renal vascular anatomical structure can be achieved to further improve the surgical safety and efficiency.

Refractory hypertension caused by renal artery fibromuscular dysplasia in one child / 临床儿科杂志

Objective To explore the clinical characteristics, diagnosis and treatment of refractory hypertension caused by renal artery fibromuscular dysplasia (FMD) in children. Method The clinical data of a child with refractory hypertension caused by FMD were retrospectively analyzed. Results A boy, with onset at age of 4 years, had significantly increased blood pressure and decreased serum potassium. His renin and angiotensin levels were significantly elevated. The boy was diagnosed with renovascular hypertension by color Doppler ultrasonography, enhanced thoracoabdominal CT and vascular reconstruction. Oral administration of a variety of antihypertensive drugs is not effective. The child was finally diagnosed of refractory hypertension caused by FMD using renal angiography. The child was not suitable for surgery. After adjusting the antihypertensive drugs, the blood pressure of the child tended to be stable. The boy received continuous follow-up for 8 years. The antihypertensive regimen was adjusted annually and blood pressure fluctuations and target organ damage were dynamically assessed. Conclusion Children with FMD caused renal vascular hypertension may have no specific manifestations in the early stage. The drug treatment is preferred, and surgical treatment may be considered.

Relationship between renal vascular resistance index and serum apelin level in type 2 diabetic mellitus / 中国综合临床

Objective To investigate the relationship between renal vascular resistance index( RI) and serum Apelin level in type 2 diabetic mellitus ( T2DM )?Methods Seventeen cases newly diagnosed T2DM patients with RI increased but without microalbuminuraia in Minhang Hospital Affiliated to Fudan University from December 2011 to December 2014 were selected as observation group,17 newly diagnosed T2DM patients with RI normal during the same period were selected as control group?Fasting plasma glucose(FPG),glycosylated hemoglobin A1C(HbAlC),blood lipids and fasting insulin(FINS),hepatic functional and renal function were tested in all the subjects?Serum Apelin level was detected by enzyme?linked immunosorbent assay?Results Compared with control group,serum Apelin level was significantly higher in observation group((179?2±122?4)μg/L vs?(56?7±50?6) μg/L,t=3?814,P<0?05)?Partial correlation analysis showed that the RI was positive correlated with Apelin ( r= 0?364, P= 0?040 )?Conclusion The serum Apelin levels elevated in newly diagnosed T2DM patients with RI increased, and RI is positively correlated with Apelin, which indicate that Apelin play an important role in the pathophysiology of early renal damage in patients with TsDM.

Renal vascular damage and the expression of miR-145 in lupus nephritis / 临床儿科杂志

Objective To evaluate renal vascular damage (RVLs) and detect the expression of miR-145 in children with lupus nephritis (LN).Methods Clinical data of 41 cases of LN diagnosed by renal biopsy from the children with systemic lupus erythematosus (SLE) were collected. Glomerular damage score and RVLs were evaluated. The children were divided into groups according to RVLs score and pathological pattern. In situ hybridization was performed to detect the expression of miR-145 in kidney blood vessel. Differences in RVLs, miR-145 expression in the renal blood vessels and glomerular damage score were observed among the groups with different renal pathological pattern. Differences in clinical parameters, glomerular damage score and miR-145 expression in the renal blood vessels were investigated among groups with different RVLs. Results Among the groups with different pathological pattern, there was no difference in RVLs (P>?0.05) while signiifcant different were found in the expression of miR-145 and glomerular damage score (P??0.05) while a statistical different was found in the expression of miR-145 (P?

Role of vascular endothelial growth factor-a in kidney development and kidney diseases / 第二军医大学学报

The renal vascular system is vital for maintaining the normal function of kidney, and vascular endothelial growth factor-A (vEGF-A) participates in the development of renal vascular.system and is associated withvarious kidney diseases. Studies have demonstrated that down-expression of renal vEGF-A can result in reduction of microvascular density in medulla kidney, regional hypoxia, and polycythemia, and further lead to increased haemopoietin. The overexpression of vEGF- A can cause renal fibrosis and cyst formation, promoting the progress of kidney disease. Therefore, regulation of vEGF-A expression may influence the occurrence and development of kidney diseases. This review summarized the role of vEGF-A in the renal vascular system and kidney diseases hoping to provide new therapeutic strategies for kidney diseases.

Correlation and dynamic observation of ambulatory arterial stiffness index and target organ damage of hypertension / 重庆医学

Objective To observe the changes of ambulatory arterial stiffness index (AASI) and target organ damage (TODs) after antihypertensive treatment in hypertensive patients .Methods A total of 300 cases of newly diagnosed hypertension were screened out and after strictly controlling blood pressure ,completed the ambulatory blood pressure and target organ damage inspection by 1‐year follow‐up .The dynamic changes of AASI and target organ damage were observed .Results After 1‐year anti‐hypertensive therapy ,AASI showed the gradually descending trend ,compared with before treatment ,began to decline at 6 months , decreased significantly after 1 year ;AASI showed the independent positive correlation with the intima‐media thickness(IMT) of ca‐rotid artery ,urine microalbumin(UMA) ,renal vascular resistance index(RRI) and left ventricular mass index(LVMI) ,and inde‐pendent negative correlation with endogenous creatinine clearance rate(Ccr) before and after treatment ;the multiple linear regres‐sion analysis showed that IMT ,UMA ,RRI ,Ccr and LVMI had significant correlation with AASI .After 1 year of therapy ,IMT , UMA ,RRI ,Ccr ,LVMI had shown some improvement(P<0 .05) .Conclusion AASI can be used as an indicator for evaluating arte‐riosclerosis and predicting the target organ damage in hypertension .

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

Renal vascular hypertension

This is a report of 7 cases of renal vascular hypertension. In 4 of these 7 cases, the diagnosis was not even thought of and was made only at autopsy. Among the three correctly diagnosed patients, one was a 26 year-old woman with an aneurysm of the left renal artery which was resected followed by renal artery replacement with a Dacron prosthesis graft with alleviation of her hypertension. The second was a 20 year-old female medical student with extreme hypoplasia at the left renal artery and kidney. Nephrectomy cured her hypertension. The third was a 19 year-old female with bilateral renal artery obstruction at their origins from the aorta. Surgical relief was obtained by endarterectomy and widening of renal artery origin using Dacron patchesThe clinical picture, useful laboratory aids, indications for aortography, surgical anatomy, physiology, surgical procedures, histology, and results of others are cited and discussed. (Summary)

Clinical Significance of the Renal Angiography / 대한비뇨기과학회지

Renal angiography has applications in the diagnosis of renal tumor and renovascular hypertension, and provides important anatomical information that can influence the surgical management. Recently the approach to the vascular system for diagnosis by means of Seldinger technique hag been expended to include a variety of therapeutic manner. So, embolization of renal carcinoma is being used with increasing frequency. Radiologic findings associated with presenting symptoms and signs were analysed in 51 cases of renal angiography, during the period of October 1978 to October 1982. The following results were obtained. 1. Male to female ratio was approximately 1:1 and peak incidence was in the sixth decade. 2. The main symptoms and signs of patients were hematuria, flank pain, hypertension and palpable mass, in order of frequency. 3. In 7 hypertensive patients with delayed visualization on the excretory urogram. angiography shows 2 cases of renal artery stenosis, one case of Takayasu's disease and absence of abnormal vasculature in 4 cases. 4. It is suggested most valuable technique for correct diagnosis of renal vascular disease. some of other congenital anomalies, and renal vascular mapping for renal surgery.