Involvement of renin-angiotensin system in hypertensive effect of cadmium in rats

Role of renin-angiotensin system in hypertension induced by cadmium chloride (CdCl2) in rats has been investigated. Intravenous administration of CdCl (1 mg/kg) produced a biphasic response i.e. a transient fall followed by a marked and consistent rise in blood pressure. The peak hypertensive effect was accompanied by raised PRA levels. Pretreatment with captopril (1 mg/kg, i.v.) losartan (1 mg/kg, i.v.) or captopril + losartan attenuated the pressor response to Cd by 62%, 42% and 100% respectively in separate groups. Central administration of Cd (10 micrograms/rat, i.c.v.) showed a biphasic response similar to that observed after i.v. route. However, it was not accompanied by raised PRA levels. Prior treatment with losartan (10 micrograms/rat, i.c.v.) completely abolished the pressor response to Cd (i.c.v.) whereas it was not affected significantly by captopril (10 micrograms/rat, i.c.v.). On the other hand, centrally administered losartan only partially reduced the pressor response to i.v. Cd. The results are discussed in light of a differential involvement of central vs peripheral renin-angiotensin system in the hypertensive effect of Cd.     

Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria

The clinical importance of selection of different antihypertensive drugs for the treatment of diabetic patients is still unclear. Thus we performed a randomised, controlled study in 105 hypertensive non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria over 1 year. Patients received either the angiotensin converting enzyme (ACE) inhibitor ramipril (2.5-5.0 mg/day; in addition 24% of patients also received felodipine) or the beta blocking agent atenolol (50-100 mg/day; in addition 24% of patients also received hydrochlorothiazide). Blood pressure, metabolic control, lipid levels and albumin excretion rate were studied during the follow-up. After 1 year an almost identical fall (p < 0.001) in blood pressure was observed with ramipril (170/100 vs 150/ 85 mmHg, median) and atenolol (180/100 vs 150/ 80 mmHg, median). With ramipril a reduction of total cholesterol (6.3 vs 5.9 mmol/l), of LDL cholesterol (3.8 vs 3.6 mmol/l) and HDL cholesterol (1.3 vs 1.2 mmol/l) was found, whereas triglycerides slightly increased (1.8 vs 2.0 mmol/l). With atenolol a similar reduction of total cholesterol (6.3 vs 5.9 mmol/l), LDL cholesterol (3.8 vs 3.7 mmol/l) and HDL cholesterol (1.4 vs 1.2 mmol/l) and an increase of triglycerides (1.4 vs 1.7 mmol/l) was noted. Metabolic control of the patients was maintained with both ramipril and atenolol treatment. With ramipril treatment urinary albumin creatinine ratio (14.4 vs 13.8 mg/mmol) and creatinine clearance (82 vs 84 ml/min) were constant, but with atenolol an increase of albumin creatinine ratio (13.9 vs 19 mg/mmol, p < 0.001) and a slight decrease of creatinine clearance (80 vs 66 ml/min, p < 0.05, not significant after Bonferroni correction) was observed. In conclusion: 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar. Despite almost identical blood pressure reduction in both groups the albumin creatinine ratio was constant under ramipril, but increased under atenolol treatment.     

Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients

There are many researchers engaged in qualitative research who look to experts in this mode of inquiry to validate their findings. But can any outsider, even an "expert" in qualitative research, do this? Such an expert is unlikely to know the data as well or to be as fully immersed in the project as the researcher. There are different kinds of expertise that may be required for different phases and purposes of research, and to satisfy different epistemological and ethical concerns. Moreover, new modes of participatory research have complicated the role of expert and the idea of expertise. Researchers must be judicious in their claims to expert validation, and experts must move researchers away from a preoccupation with validation toward craftsmanship and accountability to diverse communities.     

Role of the brain renin-angiotensin system in the maintenance of blood pressure in conscious spontaneously hypertensive and sinoaortic baroreceptor-denervated rats

1. Evidence suggesting an involvement of the brain renin-angiotensin system (RAS) in the development/maintenance of hypertension in spontaneously hypertensive rats (SHR) relies, in part, on early experimental data reporting centrally mediated antihypertensive effects of saralasin. However, recent data using non-peptide AT1 receptor antagonists does not always support this theory because these compounds usually do not lower blood pressure when given centrally. 2. In the present study we have re-assessed the central effects of saralasin in conscious SHR as well as in sinoaortic baroreceptor-denervated (SAD) rats. Both of these models exhibit heightened sensitivity to the central pressor effects of angiotensin II (AngII) and, thus, any potential antihypertensive activity would provide functional evidence of activated brain RAS mechanisms in these models. 3. In SHR, saralasin failed to lower mean arterial pressure (MAP) when given intracerebroventricularly (i.c.v.) as bolus or infusion doses that blocked the centrally mediated pressor effect of AngII. 4. In SAD rats, there was a marked impairment of the baroreceptor-heart rate reflex function and enhanced centrally mediated pressor responses to AngII. However, i.c.v. saralasin infusions again did not alter MAP. 5. Collectively, these results suggest that the central RAS is not involved in the maintenance of MAP in SHR and SAD rats, both of which are models exhibiting a functional hyperresponsiveness to AngII.     

Investigations on the renin-angiotensin system in acute severe asthma

The renin-angiotensin system is activated in acute severe asthma. The precise mechanism of activation is at present unknown, but may involve, beta2-agonists, catecholamines or proteases released in airway inflammation. This study aims to identify potential factors involved in the activation of the renin-angiotensin system in acute asthma. Forty asthmatics with severe exacerbations of asthma, assessed by measurement of peak expiratory flow rate (mean (SD) 35 (18)% predicted), oxygen saturation (94 (4)%) and pulse rate (108 (16) beats x min(-1)) were recruited. Nineteen (48%) asthmatics had elevated plasma angiotensin II levels (median (interquartile range) 10.9 (4.3-23.5) pg x mL(-1) (normal range 3-12 pg x mL(-1))) and 10 (25%) had elevated plasma renin concentration (22.0 (10.0-50.0) microU x mL(-1) (normal range 9-50 microU x mL(-1))). Plasma renin and angiotensin II correlated strongly, implying renin-dependent angiotensin II formation. No correlation was found between plasma salbutamol, adrenaline, nor-adrenaline, endothelin-1, histamine, eosinophilic cationic protein, serum angio-tensin-converting enzyme (ACE) activity, total immunoglobulin E (IgE), urea and electrolytes, indicators of the severity of the attack, atopic status, blood pressure and renin or angiotensin II levels. We conclude that although a subpopulation of asthmatics appear to have raised renin and angiotensin II during attacks of acute, severe asthma, the mechanism of activation of the renin-angiotensin system remains unclear.     

Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats

This study investigated spectral differences in the phonation of vowels between a group of 21 children with velopharyngeal impairment and a paired control group of 42 subjects. The speech material was composed of the isolated vowels /a/, /i/, and /u/, a sustained vowel /a/, and four vowels included in spoken words: two nasals /in/ and /on/ in dindon, and two orals /a/ and /o/ in gateau. A bottom-up discriminant function analysis indicated that the cepstrum coefficients and the linear-FFT were the most efficient tools in the test to classify the set of children. They were superior to the results obtained with the formant-representation of the vowels. The use of a perceptive scale (barks) did not improve the results. Discrimination over the total group showed percentages lower than those obtained when boys and girls were assessed separately. The best discriminating results were obtained with the /a/ of gateau for the girls and with the isolated /i/ for the boys.     

The renin-angiotensin system in diabetic nephropathy: the endothelial connection

Aspergillus species exhibit a distinct and clear fluorescence in Papanicolaou-stained cytological samples. The Papanicolaou (PAP) stain enhances the autofluorescence of cultured aspergilli and allows better cytological recognition of the fungus by fluorescence microscopy when it is not easily discerned from its surroundings by light microscopy. Morphological properties can be better distinguished and facilitate the differentiation of aspergillus organisms from other filamentous fungi. Neither light nor fluorescence microscopy, the cytological quality nor the presence of phagocytosed hyphae in alveolar macrophages allow distinction between infection and contamination with Aspergillus species. Only the presence of eosinophilic inflammation permits a tentative diagnosis of an Aspergillus infection. In conclusion, PAP fluorescence reduces the need for special stains, is superior to and quicker than other investigative techniques and enhances the sensitivity and specificity of cytological investigation when a rapid and reliable identification of Aspergillus is needed.     

Effect of the treatment with amlodipine on left ventricular hypertrophy in hypertensive patients

BACKGROUND: Left ventricular hypertrophy (LVH) is one of the physiopathological effects of hypertension and one of the main risk factors for sudden death, myocardial infarction and congestive heart failure. Drugs to treat hypertension must not only reduce blood pressure, but also modify the facts which lead to ventricular hypertrophy. This study has been designed to assess the effect of amlodipine, a calcium-antagonist, on LVH in hypertensive patients. METHODS: 20 hypertensive patients (mild to moderate, both sexes, mean age 45.0 yr) were included in a single-blind study. After an initial, four weeks placebo period, active treatment was given (amlodipine 5 mg a day). Dose titration was made after 4-8 weeks to 10 mg a day if necessary and continued until the end of the study. Systolic (SBP) and diastolic blood pressure (DBP), as well as pulse rate (PR) and adverse events were recorded at every visit. Blood and urine analysis, catecholamine, plasmatic renin activity and Mode M echocardiography were made at the beginning and the end of the study. RESULTS: Only one patient was excluded. SBP and DBP showed a significantly fall (p < 0.001). In 80% of patients DBP fell under 90 mm Hg. Every echocardiographic parameter, but left ventricular diastolic dimension, showed significantly reductions at the end of the study: septum thickness (p = 0.001), posterior wall thickness (p = 0.001), left ventricular systolic dimension (p = 0.014), wall relative thickness (p = 0.015), shortening fraction (p = 0.009), left ventricular mass (p = 0.001) and corrected left ventricular mass (p = 0.001). Blood parameters did not modify. CONCLUSIONS: Amlodipine has a beneficial effect on LVH and also is an effective and safe drug to treat mild to moderate hypertension.     

Therapeutic effects of prolonged normovolemic hemodilution in patients with Raynaud's disease

51 patients with Raynaud's disease has undergone prolonged normovolemic hemodilution (PNH) with a good effect. Disappearance of painful syndrome in 78.43% of cases, and a significant decrease of pains in 21.37% of cases was demonstrated. Complete healing of ulcero-necrotic defects of end phalanges of the hands was observed in 7 patients of 10 and partial--in 3. A significant remission of the disease in follow-up period was obtained. Thus, prolonged normovolemic hemodilution has resulted in significant improvement of short- and long-term results of treatment in patients with Raynaud's disease.     

Oscillatory potentials of the electroretinogram in hypertensive patients with different antihypertensive treatment

Three-dimensional structures of laterally aggregated bundles of collagen molecules, segment-long-spacing (SLS) crystallites, were imaged by atomic force microscopy (AFM) in atmosphere. The overall image of the type I collagen SLS in a height-amplified mode was semi-cylindrical, approximately 300 nm in length, with two bands of elevation near both N- and C- ends of the molecule. Its 'cross-sectional' profile (across the molecular axis) was a smooth arch. The 'axial' profile (along the molecular axis) had two prominent peaks approximately 250 nm apart, corresponding to the two bands of elevation. There were several minor peaks between these two prominent peaks. The elevation near both ends may be due to the presence of covalently bound sugars near both N- and C- ends of the helical part of type I collagen alpha chains. The AFM images of SLS presented here indicate that the type I collagen molecule is not uniform in diameter and has two bulged parts within its triple helix.     

Impact of salt intake on blood pressure and proteinuria in diabetes: importance of the renin-angiotensin system

Patients with hypertension and diabetes are frequently salt-sensitive. Consequently, increasing dietary salt intake results in a rise in systemic arterial pressure and an increase in proteinuria, as well as a progressive risk for developing renal injury. A difference in the renal hemodynamic response to salt appears, at least in part, to determine how the salt intake affects blood pressure. Greater dietary salt intake in salt-sensitive patients results in a blunted rise in renal plasma flow and an increase in body weight. Greater dietary salt consumption also results in a rise in glomerular filtration fraction and increasing proteinuria. Pharmacologic antagonism of the renin-angiotensin system helps restore the blunted renal plasma flow response to high salt intake and correlates with the fall in mean arterial pressure. Consequently, the pressor response to increasing dietary salt consumption in patients with diabetes and hypertension may be related to insufficient renal vasodilation, perhaps due to inadequate suppression of the renin-angiotensin system. Moreover, inadequate suppression of the renin-angiotensin system within the kidney results in an increase in efferent glomerular arteriolar tone and a rise in glomerular capillary pressure, increased proteinuria and a greater risk for renal injury. Many of the coexisting cardiovascular risk factors associated with salt sensitivity may be explainable in part by the overactivity of the renin-angiotensin system.     

Salt sensitive blood pressure and the renin-angiotensin system in hypertension

The relationship between (excessive) use of sodium chloride and the blood pressure is still equivocal. Blood pressure responses to alterations in dietary salt consumption vary greatly between individuals, which has led to the concept of salt sensitivity. Although the mechanisms which determine the degree of salt sensitivity are not fully understood, the renin-angiotensin system seems to play a key role. A relative inability of this system to respond promptly to alterations in salt intake may underlie the development of salt sensitivity. By administering drugs which block the renin-angiotensin system to patients with essential hypertension, blood pressure is rendered more sensitive to the effects of salt restriction and (or) diuretic treatment.     

The effect of indomethacin and other anti-inflammatory drugs on the renin-angiotensin system

The administration of two different doses of indomethacin, 9 and 18 mg/kg, to two different groups of rabbits was followed 6 h later by a significant decrease in plasma renin activity, and these levels were not increased by hemorrhage. The administration of 2 mg/kg of indomethacin did not alter the basal levels of plasma renin activity, but it was effective in diminishing the peripheral increase of renin produced by hemorrhage. Similar effects were obtained in other groups of rabbits treated with 9 mg/kg of meclofenamate or 18 mg or aspirin. The lowering effect of indomethacin on plasma renin activity is not specifically related to hemorrhage because it also prevented the increase in plasma renin activity elicited by 5 mg/kg of furosemide. Further studies showed that indomethacin did not exert any significant effect in vivo on the plasma level of renin substrate or on the generation of angiotensin from normal plasma by exogenous renin. And indomethacin did not interfere with the binding capacity of anti-angiotensin I for angiotensin I in the radioimmunoassay reaction or with the in vitro formation of angiotensin from hog renin-nephrectomized rabbit plasma reaction. The results thus indicate that the lowering effect of indomethacin on plasma renin activity is due to the interference with renal renin release. That this effect may be related to the blockade of prostaglandin synthesis is suggested by the similar effect exhibited by other blockers of prostaglandin synthesis.     

Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy

BACKGROUND: The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non-diabetic nephropathy. METHODS: The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. RESULTS: Mean arterial blood pressure decreased from 123+/-13 mmHg at baseline to 113+/-10 mmHg (P<0.01) on losartan and to 114+/-10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510+/-2586 mg/24 h at baseline to 2684+/-2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748+/-3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8+/-9.3% to 21.2+/-10.2% (P<0.05) on losartan and increased to 23.6+/-8.9% (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. CONCLUSION: Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.