Renovascular arterial hypertension. From physiopathology to therapy

Understanding the pathophysiology, diagnosis, and management of renovascular hypertension (RVH) is of paramount importance due to the severity of hypertension (HT) and renal insufficiency (RI). Moreover, adequate treatment by surgery and/or endovascular intervention can improve HT and revert RI. The comprehension of the pathophysiology of RVH had its origin on the experiments of Goldblatt which led to the recognition of the renin dependent, volume dependent, and mixed types. A continuum seems to exist, from an acute phase, supported by the endocrine renin angiotensin aldosterone system, evolving towards a chronic phase sustained by the local renin angiotensin system. The involved vasoconstrictor and mitogenic mechanisms may contribute to the arterial remodeling. The most common forms of pathology, i.e. atherosclerosis, fibromuscular dysplasia (FD), and Takayasu's arteritis, and their natural history, are described. The prevalence of RVH, ranging from 0.2% to more than 25%, depending on the clinical situation, is evidenced. Clinical symptoms and signs and the most important diagnostic tests are pointed out: functional tests (captopril test, postcaptopril renography, scintigraphy, and renin determinations) and anatomical tests (intravenous digital angiography and intrarterial angiography). New imaging techniques are also referred. A diagnostic work-up based on the index of clinical suspicion is described. The therapeutic goal is the resolution of the two main problems of RVH: hypertension and ischemic nephropathy. Revascularization is becoming mandatory either by percutaneous transluminal angioplasty mostly for FD and atheromatous non-ostial stenoses, or by surgery, which is preferred for patients with ostial or peripheral stenoses, aneuryms, occlusions and concomitant aortic disease. A better knowledge of RVH allows, not only diagnosis and treatment of one of the most frequent types of secondary hypertension, but also the control of the resulting ischemic nephropathy.     

Increased plasma endothelin concentration in atherosclerotic renovascular hypertension

The aim was to investigate circulating levels of immunoreactive endothelin (ir-ET) in atherosclerotic renovascular hypertension (RVH), and to assess the role of the kidneys in its overall plasma concentration. We studied 16 hypertensive patients with renal artery stenosis evidenced by angiography and admitted to hospital for the diagnostic evaluation of RVH by renal vein plasma renin activity (PRA) determinations. The right femoral vein was catheterized to simultaneously measure PRA and ir-ET in both renal veins and inferior vena cava below the origin of the renal veins. RVH was present in 9 patients as indicated by diagnostic PRA renal vein ratios and the remaining 7 patients were considered to have essential hypertension (EH). Patients with RVH showed a marked increase in systemic plasma ir-ET concentration (10.3 +/- 0.9 pg/ml). Despite a significant increase of PRA in the vein of the ischemic (IK) versus the contralateral (CK) kidney in patients with RVH, no significant differences in ir-ET concentration were observed between both kidneys. These results indicate that patients with RVH have increased circulating levels of ir-ET. However, the higher systemic plasma ir-ET do not arise from the renal circulation, since plasma ir-ET is significantly higher in systemic circulation than in renal veins.     

Renovascular hypertension and captopril-enhanced renal scintigraphy

Renovascular hypertension (RVH) is a secondary hypertension that is caused by the renal artery stenosis and is curable by surgical treatment. Sensitivity and specificity of CRS for RVH have been reported to be in exceed of 90%. Captopril-enhanced renal scintigraphy (CRS) has become an important tool in the diagnosis of RVH. In addition, the recent reports indicate that CRS is a promising means of prognostic evaluation in re-vascularization of RVH. In this report, pathophysiological considerations, methods, diagnostic criteria, diagnostic efficacy and consideration for clinical application are reviewed.     

Relations between cardiac and vascular structure in patients with primary and secondary hypertension

BACKGROUND: Data on cardiac and vascular structure in secondary hypertension are generally scarce, and no data on the interrelations between cardiac mass and structural characteristics of the vessel wall, both in large and in small resistance arteries, are presently available. OBJECTIVES: The aim of this study was to investigate the relation between structural changes in subcutaneous small arteries, left ventricular mass and wall thickness of the common carotid artery in patients with primary and secondary hypertension. METHODS: Seventy-four subjects were included in the study: 11 patients with pheochromocytoma, 14 with primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with essential hypertension (EH) and 12 normotensive (NT) control subjects. All subjects were submitted to a biopsy of subcutaneous fat. Morphologic characteristics of subcutaneous small resistance arteries (relaxed diameter <300 microm) were directly evaluated using a micromyographic technique. All subjects were submitted to calculation of left ventricular mass index (LVMI) and common carotid artery intima-media thickness (CCIMT), using ultrasound technique. RESULTS: The correlation coefficients between the media to lumen ratio in subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients were slightly less close than those in RVH. An excess prevalence of carotid plaques in RVH was observed. CONCLUSIONS: A close relation between small resistance artery morphology and cardiac or carotid artery structure may be observed in those hypertensive patients in whom the renin-angiotensin-aldosterone system is activated. In constrast, in NT, EH and pheochromocytoma no significant correlation between M/L and LVMI or CCIMT was observed.     

Usefulness of angiotensin converting enzyme inhibitors in the diagnosis of renovascular hypertension. III. Evaluation of the validity of the captopril test and the reno-scintigraphic captopril test in the diagnosis of renovascular hypertension according to accepted criteria

The aim of the study was to evaluate diagnostic validity of captopril test and scintigraphic test before and after captopril for the detection of renovascular hypertension (RVH) according to applied criteria. Employing blood pressure response to captopril as a criteria sensitivity was 37.0%, specificity 92.1%, positive predictive value 75.0% and negative predictive value 70.2% in the captopril test. Applying plasma renin activity (PRA) response to captopril as a criteria sensitivity was 92.5%, specificity 100%, positive predictive value 100% and negative predictive value 96.0% in the same test. Renin captopril test has excellent sensitivity and positive predictive value, is easy to perform and inexpensive and therefore may be a useful screening test for RVH in unselected population. With the own criteria used, captopril renoscintigraphy detected RVH with 87.5% sensitivity, 91.7% specificity, 87.5% positive predictive value and 91.7% negative predictive value. Captopril renoscintigraphy is an accurate diagnostic test for the identification of RVH in a clinically selected high-risk population. Common evaluation of both tests does not improve their accuracy in diagnosis of RVH.     

Angiography in non-traumatic brain haematoma. An analysis of 100 cases

PURPOSE: The primary purpose of this project was to study the anatomical characteristics of intracerebral haematoma (ICH) in order to determine features that may negate the need for angiography in some patients. MATERIAL AND METHODS: The study was prospective and designed to investigate the underlying cause of non-traumatic ICH in 100 cases assessed by conventional angiography. Patients were excluded if there was a history of trauma or known pre-existing brain abnormality. All patients were examined with CT and angiography within 4 days of the ictus. RESULTS: Ruptured aneurysms or arteriovenous malformations (AVMs) were diagnosed on the initial angiogram in 49% of cases: 27 AVMs and 22 aneurysms. One case of superior sagittal sinus thrombosis was also detected. Vascular abnormalities were found most frequently in the under-40 age group and in cases in which subarachnoid haemorrhage, intraventricular haemorrhage or extracerebral haematoma accompanied the ICH. The temporal lobe was the most frequent anatomical location (37%). When a temporal lobe haematoma extended into the Sylvian fissure from the inferior pole of the temporal lobe or when it was associated with subarachnoid haemorrhage, structural abnormalities were found in over 90% of cases. CONCLUSIONS: There are groups of patients with ICH in whom the CT features are highly suggestive of AVM or aneurysm rupture. If the initial angiography is negative in these cases, careful follow up by repeat angiography and/or MR imaging is essential. However, potentially treatable abnormalities cannot be excluded with certainty by the distribution of the haematoma on CT alone, even if there is a history of pre-existing hypertension.     

Prevalence and risk factors for diabetic retinopathy among Omani diabetics

To determine the minimal contrast dosage required for diagnostic contrast-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) image quality of the pulmonary (PAs) or renal arteries (RAs). In 12 volunteers (10 females, 2 males; mean age 24 years) imaging was performed with 4 different dosages: 0.05, 0.1, 0.2 and 0.3 mmol/kg of body weight (BW) 0.5 M gadolinium (Gd) contrast agent. The PAs and RAs were evaluated separately each in groups of six volunteers. Qualitative and quantitative signal-to-noise ratio (SNR) image analysis was performed. For the PAs, the increases in signal-to-noise ratio were paralleled by increases in image quality ratings. For the PAs, with the use of 0.05 mmol/kg, only 50.3% of all segments were rated diagnostic, whereas with higher dosages the percentage rose to 89.2% for 0.1 mmol/kg, 98.2% for 0.2 mmol/kg. and 99.1% for 0.3 mmol/kg. For the RAs, 0.3 mmol/kg provided no significant increase in singal-to-noise ratio compared to 0.2 mmol/kg (p = 0.4). Only by a dosage of 0.2 and 0.3 mmol/kg, all evaluated segments were diagnostic evaluable. A dose of 0.2 mmol/kg is required for proper assessment of the RAs or PAs.     

Intravascular ultrasonic characteristics and vasoreactivity of the pulmonary vasculature in children with pulmonary hypertension

We sought to describe the morphologic characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in children with and without pulmonary hypertension to compare these anatomic findings with those of pulmonary wedge angiography, and to determine the relation between these structural findings and functional reactivity to pulmonary vasodilators. Direct evaluation of pulmonary vascular structure in children with pulmonary hypertension with current imaging techniques has been limited and little is known about the relation between structural and functional characteristics of the pulmonary vasculature. In 23 children undergoing cardiac catheterization (15 with pulmonary hypertension and 8 controls) we performed IVUS and pulmonary wedge angiography of the distal pulmonary arteries in the same lobe. IVUS was performed in 44 pulmonary arteries measuring 2.5 to 5.0 mm internal diameter with a 3.5Fr 30-MHz IVUS catheter. We assessed vasoreactivity to inhaled nitric oxide (NO) and oxygen in 13 of 15 children with pulmonary hypertension. Baseline pulmonary vascular resistance (PVR) was greater in the 15 children with pulmonary hypertension than in the 8 controls (9.5+/-1.9 vs 1.5+/-0.3 U x m2, p <0.05). NO lowered PVR in patients with pulmonary hypertension (p <0.05). IVUS studies in patients with pulmonary hypertension showed a thicker middle layer, wall thickness ratio, and diminished pulsatility than did those in controls (p <0.05). The inner layer was not visualized by IVUS in any control patient, but was seen in 9 of 15 patients with pulmonary hypertension. Pulmonary artery wedge angiography correlated with baseline mean pulmonary artery pressure and PVR as well as with IVUS findings of wall thickness ratio and inner layer thickness. The inner layer was not visualized by IVUS in any patient with grade 1 wedge angiograms or in 86% of patients with grade 2 wedge angiograms. All patients with grade 4 and 80% of patients with grade 3 wedge angiograms had a visible inner layer. Vasoreactivity to NO and oxygen did not correlate with structural assessment of the pulmonary vasculature by IVUS. Structural changes in the pulmonary arteries in children with pulmonary hypertension can be directly visualized by IVUS, but are not predictive of NO-induced pulmonary vasodilation. IVUS examination of pulmonary arteries may complement current techniques utilized in the evaluation of children with pulmonary hypertension.     

Calcium transients in single myocytes and membranous ultrastructures during the development of cardiac hypertrophy and heart failure in rats

1. We examined changes in intracellular calcium transients of separated single myocytes from the right ventricle (RV) of the rat heart during the change from adaptation to maladaptation in response to a pressure overload. 2. Right ventricular hypertrophy (RVH) secondary to pulmonary hypertension was induced by a subcutaneous injection of monocrotaline. Developed tensions of the RV-free wall were decreased as RVH progressed. Single myocytes were separated from the RV during different stages of RVH. Fura-2/AM-loaded cells were field stimulated, and changes in calcium transients were measured by Olympus OSP-3 system. We also examined membranous ultrastructures (sarcoplasmic reticulum, mitochondria, surface caveolae) involved in calcium metabolism in the hearts using scanning electron microscopy. 3. We observed characteristic changes in calcium transients during the change from adaptation to maladaptation, and also found that one parameter (amplitude) of calcium transients appeared to be correlated with the changes in the number of sarcoplasmic reticulum. 4. These results provided some insights into the mechanism of calcium handling of hypertrophied heart in response to a pressure overload from adaptation to maladaptation especially when stimulatory frequency was high, and suggested that heart rate control is a very important factor for the treatment of patients with congestive heart failure.     

Renovascular hypertension: anatomic and renal function changes during drug therapy

Serial renal function studies were performed on 41 patients wtih renovascular hypertension (RVH) secondary to atherosclerotic renal artery disease who had been randomly selected for nonoperative management. In 19 patients, serum creatinine levels increased between 25% and 120%. The glomerular filtration rates dropped between 25% and 50% in 12 patients. Fourteen patients (37%) lost more than 10% of renal length. In four patients (12%), a significant stenosis progressed to total occlusion. Seventeen patients (41%) had deterioration of renal function or loss of renal size that led to operation. One patient required removal of a previously reconstructible kidney. Of the 17 patients with deterioration, 15 had acceptable blood pressure (BP) control during the period of nonoperative observation. Progressive deterioration of renal function in nonoperatively treated patients with atherosclerotic renal artery stenosis and RVH is common, and occurs even in the presence of BP control with drugs.     

Biochemical and genotoxic responses of adult eel (Anguilla anguilla L.) to resin acids and pulp mill effluent: laboratory and field experiments

The potential of a secondary-treated bleached kraft pulp mill effluent (BKPME) and resin acids (RAs) to induce liver ethoxyresorufin-O-deethylase (EROD) activity and erythrocytic nuclear abnormalities (ENAs) in adult Anguilla anguilla L. was investigated in laboratory and field experiments. Hepatic health was assessed by measurement of liver alanine transaminase (ALT). One single intraperitoneal injection of abietic acid (AA) or dehydroabietic acid (DHAA), at the same molar dose (14.7 micromol/kg), was given and fish were examined 3 days later. Only AA induced a significant increase in EROD activity while both RAs significantly increased the frequency of ENAs. A 3-day dose-response experiment (concentration range up to 2.7 microM) was also carried out for the same two water-diluted RAs. Both RAs induced a dose-related significant increase in EROD activity, presenting the same NOAEL (between 0.03 and 0.1 microM), while liver ALT activity significantly decreased. Both RAs revealed a mutagenic potential, measured as induction of ENAs, displaying the same NOAEL (between 0. 1 and 0.3 microM). A laboratory experiment with 3 days of BKPME exposure revealed NOAELs between 12.5 and 25% for EROD activity and between 6.25 and 12.5% for ENA frequency. An additional laboratory experiment with 50% BKPME demonstrated that the minimal time necessary to induce a significant increase in EROD activity in the eel was 6 h. In a field experiment, caged eels were exposed in the river, at different distances (left bank: site 1-50 m; right bank: site 2-100 m, site 3-600 m, site 4-2000 m) from the BKPME sewage outlet. Liver EROD activity significantly increased at 1 and 3 days of exposure, with the exception of site 2, whereas ENAs were induced after 3 days of exposure at site 3.     

The investigation of renovascular hypertension in children: the accuracy of radio-isotopes in detecting renovascular disease

Renovascular disease is an important cause of hypertension in children because it is potentially treatable by surgical or angioplasty techniques. The aim of this study was to assess the accuracy of radio-isotopes (DMSA, DTPA and MAG3) combined with the angiotensin converting enzyme inhibitor, captopril, in detecting children with renovascular hypertension. We retrospectively reviewed the ultrasound and pre- and post-captopril radionuclide studies (either DMSA and/or DPTA and/or MAG3) of children with sustained hypertension investigated at our institution. Renal angiography was used as the 'reference technique'. Thirty-nine children, over a period of 10 years, were evaluated: 17 (44%) children had renovascular disease that involved the proximal three divisions of the renal arteries, some of which were amenable to treatment. The overall sensitivity, specificity, positive predictive value and negative predictive value for detecting such renovascular disease, as assessed by changes between pre- and post-captopril radio-isotope studies, were disappointing at 59%, 68%, 59% and 68%, respectively. When considering only abnormalities in post-captopril studies, these indices were 82%, 41%, 52% and 75%, respectively. Three children with potentially treatable renovascular disease were not identified on the captopril studies. We conclude that renal angiography should remain the 'reference technique' in identifying children suspected of renovascular hypertension.     

Auditory response areas altered by intermodulation distortion products from background tones

Response areas (RAs) of sensory neurones are dynamically modified by attention, denervation of specific afferent input, blocking inhibition, and by prolonged conditioning with extra-RA stimuli. Here we demonstrate in auditory neurones that the RA is also critically influenced by the background to stimuli. When RAs are measured in the presence of non-excitatory extra-RA tones, new RAs arise at frequencies otherwise not excitatory, as a consequence of non-linear receptor organ transduction. The new RAs can become more sensitive than the RA in quiet conditions such that neurones are then effectively tuned to a new frequency. Thus, even in a modestly complex environment, auditory neurones do not signal a fixed range of sounds but effectively code sounds to which they are otherwise unresponsive.     

Abnormalities of mechanoreceptors in a rat model of neuropathic pain: possible involvement in mediating mechanical allodynia

1. Peripheral nerve injury sometimes leads to the development of neuropathic pain. One of the symptoms of such neuropathic pain is mechanical allodynia, pain in response to normally innocuous mechanical stimuli. We hypothesized that sympathetically driven dysfunction of cutaneous mechanoreceptors is responsible for signaling mechanical allodynia. The present study was undertaken to identify the types of sensory receptors that potentially mediate mechanical allodynia, with the use of a rat neuropathic pain model we have developed. 2. One week to 10 days after tight ligations of the L5 and L6 spinal nerves on one side, the rats fully developed behavioral signs of mechanical allodynia on the affected hindlimb. Various cutaneous mechanoreceptors originating from the neuropathic foot were examined by single-fiber recordings from the L4 dorsal root. 3. Although no particular abnormalities were found in other types of cutaneous mechanoreceptors, an unusual type of mechanoreceptor was found to be innervating the neuropathic foot. The response characteristics of this type of receptor resemble those of rapidly adapting mechanoreceptors (RAs), but with low and irregular static discharges during a maintained mechanical stimulus. We termed this unusual type as a "modified rapidly adapting" mechanoreceptor (MRA). 4. The response characteristics of MRAs change to those of typical RAs after a systemic injection of phentolamine, an alpha-adrenergic receptor blocker. 5. We conclude that many RAs become abnormal under the influence of sympathetic efferents in neuropathic pain, so that their response patterns change to those of MRAs. We propose that this abnormality is responsible for signaling the mechanical allodynia that can be seen in neuropathic pain states such as causalgia.     

Pattern electroretinogram and optic nerve topography in ocular hypertension

It is known that changes in pattern electroretinogram (PERG) and optic disk morphology may both precede the onset of visual field damage in glaucomatous disease. However, the relationship between PERG and optic disk morphometry in ocular hypertension (OHT) has not yet been evaluated in detail. This study of PERG amplitude in a group of OHT patients indicates its significant correlation with various optic disk morphometric parameters, in particular, those of optic disk sectors considered at risk for early glaucomatous damage. Analysis of individual data points to the possibility that, while functional abnormalities may often precede optic disk morphologic changes, in a much lower number of cases it seems to be the other way around.     

The role of H2-receptor antagonists in the pathogenesis of nosocomial pneumonia in mechanically ventilated patients

We conducted a computerized MEDLINE search and selected controlled studies and meta-analyses correlating the frequency of nosocomial pneumonia (NP) with the administration of histamine2-receptor antagonists (H2RAs) as stress ulcer prophylaxis in critically ill patients. Although such a correlation does exist, the literature supports the theory that gastric bacterial overcolonization through alkalinization by H2RAs is not a risk factor for NP in critically ill patients. Further well-designed studies are necessary to resolve the issue and clarify the role of H2RAs in the pathogenesis of NP.     

Diagnostic value of ECG patterns of right ventricular hypertrophy in children

OBJECTIVE: To determine the diagnostic value of traditional criteria of right ventricular hypertrophy (RVH) in children. PATIENTS: The electrocardiograms (ECGs) of 1000 consecutive pediatric patients were reviewed. Children under three months old were excluded as were patients with QRS prolongation. RESULTS: Four hundred and thirty-four patients met all inclusion criteria. The medical records were then reviewed for diagnosis. Sixty-seven per cent had a diagnosis compatible with RVH. Of the ECG patterns evaluated, a precociously upright T wave in lead V1 was most predictive with 99% specificity. Presence of a QR complex in lead V1 had a 96% specificity but R:S ratio, voltage criteria and rSR' incomplete right bundle branch block pattern had intermediate specificities of 66%, 66% and 52%, respectively. Sensitivities of 12.6%, 13.2%, 34.0%, 63.3% and 74.2% were calculated for upright T, QR complex, R:S ratio, voltage criteria and rSR', respectively. CONCLUSIONS: An upright T wave or qR pattern are highly specific but insensitive markers of RVH in children. In contrast, when an incomplete right bundle branch block exists, the rSR' pattern is a relatively sensitive but nonspecific predictor of RVH.     

Interpersonal stress, depression, and disease activity in rheumatoid arthritis and osteoarthritis patients

The relationships among interpersonal stressors, depression, coping inefficiency, hormones (prolactin, cortisol, and estradiol), and disease activity were examined. The sample comprised 33 women with rheumatoid arthritis (RAs; age 37-78) and 37 women with osteoarthritis (OAs; age 47-91), who served as controls. In a regression analysis, interpersonal conflict events accounted for more than twice as much variance in depression in RAs than in OAs. In the RA patients, the immune-stimulating hormones prolactin and estradiol were significantly positively correlated with interpersonal conflicts, depression, coping inefficacy, and clinician ratings of disease activity, suggesting that RAs are more reactive to interpersonal stressors than are OAs, both psychologically and physiologically.     

Computed tomographic angiography of the thoracic vessels: the method, initial experience and outlook for its use

The paper presents the data available in the literature on computed tomographic angiography and the first experience with it to study thoracic vessels. It details the principles of spiral computed tomography and CT angiography. Practical aspects of their implementation, as well as basic concepts are outlined. It is concluded that CT angiography is promising in studying thoracic vessels in various abnormalities.     

Preoperative coronarography in heart valve disease patients. A probability analysis of coronary lesion

INTRODUCTION AND OBJECTIVES: The indication of preoperative coronary angiography is routinely performed for patients who are going to valve replacement surgery. The need of coronary angiography is based on age, gender and previous angina, but it is not usually based on risk factors. The purpose of this study has been to find markers to predict the probability of coronary lesion in this group of patients. PATIENTS AND METHODS: We studied retrospectively a population of 541 patients with valvular heart disease who underwent preoperative coronary angiography from 1989 to 1994. Mean age was 61.8 (range 34-82). There were 301 men and 240 women. We analyzed in each patient different variables such as age, gender, previous angina, hypertension, diabetes mellitus, tobacco and familial predisposition. We correlated these variables with the presence of coronary lesion by multivariate analysis. RESULTS: There were 73 patients with coronary lesion greater than 50%. The prevalence of significant coronary artery disease was 13.4%. Angina was present in 34.6%. The risk of coronary lesion was defined as odds ratio: previous angina 3.3; tobacco 2.6; diabetes 2.2; hypertension 1.8 and age 1.4. The others variables were not predictor of coronary lesion. The probability of coronary lesion in patients without those variables (angina, tobacco, diabetes, hypertension) was 4%. If we analyzed age, the probability of coronary lesion was 3% in patients under 65 years and 6% above 65 years. CONCLUSIONS: The lack of previous angina and at least the three risk factors described as predictors of coronary lesion (hypertension, tobacco and diabetes) can define a group of patients with a very low prevalence of coronary lesion, especially if they are under 65 years. It can allow us to avoid preoperatory coronary angiography in patients who undergo valve replacement.