Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease

Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease. The cardiovascular pressor responsiveness to infused norepinephrine (NE) or angiotensin II (AII) as related to endogenous plasma NE or renin levels was assessed in 20 patients with mild parenchymal kidney disease (plasma creatinine 2.20 ± 0.58 mg/dl, ± SEM) and in 20 normal subjects approximately matched for sex and age. The two groups did not differ significantly in mean body weight, heart rate, blood volume, plasma electrolytes, exchangeable or urinary sodium, plasma aldosterone, epinephrine and renin levels, or AII threshold or pressor doses. Basal (including pre-infusion) plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance of NE (5.0 ± 0.8 vs. 5.5 ± 0.5 liter/min) also did not differ significantly between the two groups. In contrast, the threshold or pressor doses of infused NE decreased significantly in the patients with kidney disease (94 ± 11 vs. 134 ± 14 ng/kg/min and 21 ± 3 vs. 40 ± 7 ng/ kg/min; P < 0.05). Moreover, based on analysis of covariance, the individual pressor doses as related to basal plasma NE levels were distributed differently (P < 0.01) between the patients and normal subjects. These findings suggest that the kinetics of plasma NE are unaltered largely in early stage kidney disease. However, such patients tend to develop an exaggerated pressor responsiveness to NE in the presence of normal plasma NE levels. This disturbance may favor the development of hypertension.Stimulation de la réactivité pressive cardiovasculaire à la noradrénaline dans les néphropathies modérées. La réponse pressive cardiovasculaire après perfusion de noradrénaline (NE) ou d'angiotensine II (AII) en fonction des concentrations endogènes de NE ou de rénine plasmatiques a été étudiée chez 20 malades ayant une maladie rénale parenchymateuse modérée (créatininémie 2,20 ± 0,58 (± SEM) mg/dl) et chez 20 sujets normaux d'âge et de sexe voisins. Les deux groupes ne différaient pas significativement par le poids corporel moyen, le rythme cardiaque, le volume sanguin, les électrolytes plasmatiques, le sodium échangeable ou urinaire, l'aldostérone plasmatique, les niveaux d'adrénaline et de rénine, ou les doses seuils ou pressives d'All. Les concentrations plasmatiques de NE basales (y compris les valeurs avant perfusion), la relation entre la NE plasmatique mesurée pendant la perfusion de NE et la vitesse de perfusion de NE correspondante, ainsi que la clearance plasmatique totale de NE (5,0 ± 0,8 contre 5,5 ± 0,5 1/ mn) ne différaient également pas entre les deux groupes. A l'inverse, les doses seuils ou pressives de NE perfusées étaient significativement diminuées chez les malades ayant une néphropathie (94 ± 11 contre 134 ± 14 ng/kg/mn et 21 ± 3 contre 40 ± 7 ng/kg/mn; P < 0,05). En outre, par analyse de covariance, les doses pressives individuelles en fonction des concentrations plasmatiques basales de NE étaient distribuées différemment (P < 0,01) entre les malades et les sujets normaux. Ces résultats suggèrent que la cinétique de la NE plasmatique est en grande partie inchangée au cours des néphropathies au stade initial. Cependant les malades tendent à développer une réponse pressive exagérée à la NE en présence de concentrations plasmatiques de NE normales. Cette anomalie pourrait favoriser le développement d'une hypertension

Cardiovascular Pressor Reactivity After Chronic Converting Enzyme Inhibition

In addition to inhibiting the formation of angiotensin II, chronic converting enzyme inhibition may affect other blood pressure modulating factors. The influence of an 8 week treatment phase with Cilazapril on the activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, the pressor reactivity to infused angiotensin II or norepinephrine, the chronotropic response to isoproterenol, and body sodium and plasma atrial natriuretic peptide concentrations was assessed in 11 normal subjects and 12 patients with essential hypertension. As compared to a 4 week placebo phase, Cilazapril decreased arterial pressure in both study groups (from 124/83 ± 9/6 to 114/77 ± 9/5 mm Hg and from 143/102 ± 13/7 to 137/96 ± 10/10 mm Hg; Ρ < .025); exchangeable sodium (−158 mmol and, respectively, −104 mmol) and upright plasma aldosterone (−24% and −15%) also tended to fall. Heart rate, the chronotropic response to posture or isoproterenol, plasma norepinephrine levels, the concentration/pressor response curve to norepinephrine, plasma atrial natriuretic peptide concentration, plasma angiotensin II and the responses of blood pressure or plasma aldosterone to angiotensin II were unchanged after 8 weeks of Cilazapril. Plasma renin activity increased (+175% to + 650%) These findings indicate that the blood pressure lowering effect of Cilazapril in the stable phase of pharmacological intervention is not associated with modifications of sympathetic-dependent pressor reactivity or ^-adrenergic sensitivity. Plasma angiotensin II concentration and angiotensin II-dependent pathways including the pressor and aldosterone responsiveness to angiotensin II are also unchanged. Am J Hypertens 1991;4:348-35

Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus

Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus. Interrelations among plasma renin activity (PRA), aldosterone and Cortisol levels, blood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P < 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P < 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.Sodium, rénine, aldostérone, catécholamines et pression artérielle dans le diabèté sucré. Les inter-relations entre l'activité rénine plasmatique (PRA), les concentrations d'aldostérone et de cortisol, le volume sanguin, le sodium échangeable, les catécholamines urinaires et la pression artérielle ont été étudiées chez 35 sujets normaux et 60 malades atteints de diabété, sans insuffisance rénale et dont les âges étaient appariés (60% avaient une hypertension et 15% une hypotension orthostatique). La PRA de base, l'aldostérone et le Cortisol plasmatiques, le volume sanguin, le potassium plasmatique et les électrolytes urinaires étaient comparables chez les diabétiques et les sujets normaux. Les malades diabétiques, cependant, ont une augmentation de 10% de leur sodium corporel (P < 0,01). Huit pour cent d'entre eux ont une réponse posturale de PRA normale et une réponse de l'aldostérone inférieure à la normale, 22% ont une réponse de PRA inférieure à la normale et une reponse de l'aldosterone normale, et 17% ont des réponses de PRA et de l'aldostérone inférieures à la normale. Les réponses de l'aldostérone sans rapport avec PRA ne peuvent pas être expliquées par l'ACTH ou les électrolytes. Les diminutions de la pression artérielle liées à l'orthostatisme sont correlées (P < 0,01) à la fois avec l'excrétion de catécholamines et la PRA de base. Ceci suggére qu'au cours du diabéte le sodium corporel est augmenté. La PRA et l'aldosterone de base sont souvent normales mais leur réponse posturale est souvent modifiée. L'absence de réponse de l'aldosterone malgré une réponse normale de PRA peut traduire une anomalie surrénale ou une forme de rénine inefficace. Une stimulation posturale importante de l'aldostérone non expliquée par la PRA, l'ACTH ou les électrolytes oriente vers un facteur inconnu mais puissant du contrôle de la sécrétion d'aldostérone. Des concentrations basses de catécholamines libres et une PRA basse peuvent être des facteurs complémentaires qui participent à l'hypotension posturale

Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus

Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus. Interrelations among plasma renin activity (PRA), aldosterone and Cortisol levels, blood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P < 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P < 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.Sodium, rénine, aldostérone, catécholamines et pression artérielle dans le diabèté sucré. Les inter-relations entre l'activité rénine plasmatique (PRA), les concentrations d'aldostérone et de cortisol, le volume sanguin, le sodium échangeable, les catécholamines urinaires et la pression artérielle ont été étudiées chez 35 sujets normaux et 60 malades atteints de diabété, sans insuffisance rénale et dont les âges étaient appariés (60% avaient une hypertension et 15% une hypotension orthostatique). La PRA de base, l'aldostérone et le Cortisol plasmatiques, le volume sanguin, le potassium plasmatique et les électrolytes urinaires étaient comparables chez les diabétiques et les sujets normaux. Les malades diabétiques, cependant, ont une augmentation de 10% de leur sodium corporel (P < 0,01). Huit pour cent d'entre eux ont une réponse posturale de PRA normale et une réponse de l'aldostérone inférieure à la normale, 22% ont une réponse de PRA inférieure à la normale et une reponse de l'aldosterone normale, et 17% ont des réponses de PRA et de l'aldostérone inférieures à la normale. Les réponses de l'aldostérone sans rapport avec PRA ne peuvent pas être expliquées par l'ACTH ou les électrolytes. Les diminutions de la pression artérielle liées à l'orthostatisme sont correlées (P < 0,01) à la fois avec l'excrétion de catécholamines et la PRA de base. Ceci suggére qu'au cours du diabéte le sodium corporel est augmenté. La PRA et l'aldosterone de base sont souvent normales mais leur réponse posturale est souvent modifiée. L'absence de réponse de l'aldosterone malgré une réponse normale de PRA peut traduire une anomalie surrénale ou une forme de rénine inefficace. Une stimulation posturale importante de l'aldostérone non expliquée par la PRA, l'ACTH ou les électrolytes oriente vers un facteur inconnu mais puissant du contrôle de la sécrétion d'aldostérone. Des concentrations basses de catécholamines libres et une PRA basse peuvent être des facteurs complémentaires qui participent à l'hypotension posturale

Cardiovascular Pressor Reactivity After Chronic Converting Enzyme Inhibition

Surfaces with built-in antimicrobial activity have the potential to reduce hospital-acquired infections. One promising strategy is to create functionalised surfaces which, following illumination with visible light, are able to generate singlet oxygen under aerobic conditions. In contrast to antibiotics, the mechanism of bacterial kill by species derived from reactions with singlet oxygen is completely unselective, therefore offering little room for evolutionary adaptation. Here we consider five commercially available organic photosensitiser dyes encapsulated in silicone polymer that show varied antimicrobial activity. We correlate density functional theory calculations with UV-Vis spectroscopy, electron paramagnetic resonance spectroscopy and singlet oxygen production measurements in order to define and test the elements required for efficacious antimicrobial activity. Our approach forms the basis for the rational in silico design and spectroscopic screening of simple and efficient self-sterilising surfaces made from cheap, low toxicity photosensitiser dyes encapsulated in silicone

Potassium and norepinephrine- or angiotensin–mediated pressor control in pre-hypertension

Potassium and norepinephrine- or angiotensin–mediated pressor control in pre-hypertension. Blood pressure (BP), plasma electrolytes, renin, aldosterone, angiotensin II (AII) or catecholamines, the chronotropic effects of intravenous isoproterenol, norepinephrine (NE) or AII, the pressor responses to NE or AII, and the relationship between plasma AII and aldosterone concentrations were studied before and after 10 days of dietary supplementation with potassium 100 mmol/day, in normotensive members of normotensive (N = 12) or hypertensive (N = 12) families, and 11 patients with borderline essential hypertension. Under control conditions, the pressor responsiveness to NE was significantly enhanced in normotensive with positive family history for hypertension and hypertensive subjects; the other variables were comparable in the groups. After potassium supplementation, plasma potassium, renin, aldosterone or AII, and the relationship between AII and aldosterone levels increased significantly, while body weight, plasma catecholamines, the chronotropic effects of isoproterenol, AII or NE, the pressor effects of AII and plasma clearance of AII or NE were unchanged in all groups. In normotensive members of hypertensive families and patients with hypertension, BP was decreased and the exaggerated pressor responsiveness to NE was normalized; these variables were not modified in normotensive members of normotensive families. These observations are consistent with a potassium-remediable disturbance in NE- but not AII-dependent regulation of BP in the pathogenesis of essential hypertension

Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a delayed-type hypersensitivity reaction to drugs. They represent true medical emergencies and an early recognition and appropriate management is decisive for the survival. SJS/TEN manifest with an "influenza-like" prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. The difference between SJS, SJS/TEN overlap, and TEN is defined by the degree of skin detachment: SJS is defined as skin involvement of  30%, and SJS/TEN overlap as 10-30% skin involvement. The diagnosis of different degrees of epidermal necrolysis is based on the clinical assessment in conjunction with the corresponding histopathology. The mortality rates for SJS and TEN have decreased in the last decades. Today, the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is available for SJS/TEN severity assessment. Drugs with a high risk of causing SJS/TEN are anti-infective sulfonamides, anti-epileptic drugs, non-steroidal anti-inflammatory drugs of the oxicam type, allopurinol, nevirapine, and chlormezanone. Besides conventional drugs, herbal remedies and new biologicals should be considered as causative agents. The increased risk of hypersensitivity reactions to certain drugs may be linked to specific HLA antigens. Our understanding of the pathogenesis of SJS/TEN has improved: drug-specific T cell-mediated cytotoxicity, genetic linkage with HLA- and non-HLA-genes, TCR restriction, and cytotoxicity mechanisms were clarified. However, many factors contributing to epidermal necrolysis still have to be identified, especially in virus-induced and autoimmune forms of epidermal necrolysis not related to drugs. In SJS/TEN, the most common complications are ocular, cutaneous, or renal. Nasopharyngeal, esophageal, and genital mucosal involvement with blisters, erosions as well as secondary development of strictures also play a role. However, in the acute phase, septicemia is a leading cause of morbidity and fatality. Pulmonary and hepatic involvement is frequent. The acute management of SJS/TEN requires a multidisciplinary approach. Immediate withdrawal of potentially causative drugs is mandatory. Prompt referral to an appropriate medical center for specific supportive treatment is of utmost importance. The most frequently used treatments for SJS/TEN are systemic corticosteroids, immunoglobulins, and cyclosporine A