extensive laboratory investigations, no other etiologic factor could be detected. The rapid BP ri... more extensive laboratory investigations, no other etiologic factor could be detected. The rapid BP rise suggested sympathetic nervous system activation. Polydipsia is frequently associated with electrolyte distrubances but pathologic BP oscillations are exceptional. Based on a review of the literature, we discuss abnormal renal volume control and an impaired central BP regulation and barorefl ex function after brain stem infarction to explain the association of polydipsia with recurrent diurnal hypertension. Conclusions: Chronic polydipsia may be rare. However, it may occasionally represent a modifi able cause of BP elevations and treatment resistance in elderly patients particularly when volume handling is impaired by comorbidity.
Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury, 1993
While the selective peptido-LT-antagonists ICI 198615 and MK 571 block the LT contractions in bro... more While the selective peptido-LT-antagonists ICI 198615 and MK 571 block the LT contractions in bronchial tissues they do not inhibit the vascular responses. These results suggest that more than one leukotriene receptor exists in man. One type is present on human airways (LT-1) and is inhibited by potent antagonists. A second type (LT-2) is present on the pulmonary veins and is resistant to these compounds. Unlike IC1198615 and MK571, LTE4 and BAY u9773 (LT-analog) antagonized LT-induced contractions on the human pulmonary veins. The clinical effect of antagonizing this second peptido-LT receptor type has yet to be assessed.
The Journal of pharmacology and experimental therapeutics, 1987
A fixed concentration of paf-acether (platelet-activating factor; 4 microM) relaxed isolated guin... more A fixed concentration of paf-acether (platelet-activating factor; 4 microM) relaxed isolated guinea pig tracheal preparations which had been contracted with histamine (50 microM), serotonin (1 microM) or leukotriene D4 (0.1 microM). The relaxations were approximately 43, 100 and 57%, respectively. We did not observe any relaxant effect of paf-acether (4 microM) in tissues contracted with acetylcholine (50 microM). Both lyso paf-acether (10 microM) and bovine serum albumin (25 micrograms/ml) were without effect on histamine-contracted preparations. In the presence of indomethacin (1.7 microM; 30 min) or aspirin (0.1 mM; 30 min) the relaxant effect of paf-acether (4 microM) in tissues contracted with histamine was significantly reduced to approximately 10 and 12%, respectively. When paf-acether (4 microM) was added to histamine-contracted tracheal preparations in the presence of noradrenaline (0.1 microM) or prostaglandin E2 (PGE2, 10 nM) the relaxations were 62 and 82%, respectively....
The Journal of pharmacology and experimental therapeutics, 1992
Leukotrienes (LT) are potent spasmogenic agents in human isolated bronchial and pulmonary venous ... more Leukotrienes (LT) are potent spasmogenic agents in human isolated bronchial and pulmonary venous muscle preparations. Treatment of human isolated pulmonary veins with the L-serine borate complex (45 mM; 30 min) did not alter the LTC4 pD2 values in these preparations. The cysteinyl LT antagonists, ICI 198615, MK 571 and SKF 104353, significantly shifted to the right the LT concentration-effect curves in airways with pKB values against LTC4 of 8.4 for ICI 198615, 8.6 for MK 571 and 8.0 for SKF 104353. Similar results were found against LTD4. In contrast, these antagonists did not inhibit the LTC4 and LTD4 contractions in human pulmonary veins. LTE4 was a partial agonist on the human pulmonary veins and blocked the contractions with a pKp value of 6.3 against LTD4 and 6.6 against LTC4. An LT analog, BAY u9773, also blocked the LT contractions in bronchial and venous muscle preparations with pKp values against LTD4 and LTC4 of 6.5 and 6.7, respectively. These data provide pharmacologica...
The authors and the publisher have exerted every effort to ensure that drug selection and dosage ... more The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indica tions and dosage and for added warnings and precau tions. This is particularly important when the recom mended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopy ing, recording, microcopying, or by any information stor age and retrieval system, without permission in writing from the publisher or. in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center (see 'Information for Readers and Subscribers').
The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylc... more The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied. Epithelium removal caused a significant leftward shift of the acetylcholine concentration-effect curve, pD2 values were 2.86 +/- 0.11 and 3.34 +/- 0.18 for intact and rubbed tissue, respectively (P < 0.05). However, there was no change in the acetylcholine maximal response. The sensitivity and responsiveness of the bovine bronchus to the other spasmogens were not significantly altered by removal of the epithelium. These results suggest that the epithelium of bovine bronchi modulates only acetylcholine-induced contraction.
-Acetylcholinesterase (AChE. EC 3. I. I .7) and butyrylcholinesterase (BChE. EC 3. I. I .8) activ... more -Acetylcholinesterase (AChE. EC 3. I. I .7) and butyrylcholinesterase (BChE. EC 3. I. I .8) activities were detected in bmnchial and bronchial epithelial cell homogenates o f the pig. In the bronchial homogenates. the maximal upstroke velocity (V,) o f AChE and the maximal velocity after second substrate fixation (V,) o f BChE were 5.70 i 0.46 and 7.87 i 0.81 mU/mg protein. respectively. In the epithelial cell homogenates. a smaller amount of cholinestcrase (ChE) was found: V , was 0.62 i 0.29 and V, was 1.56 i 0.33 mU/mg protein for AChE and BChE, respectively. AChE activity was increased by 21 i 5% in the bronchial homogenates and by 54 i 14% i n the epithelial cell homogenates. when intact bronchial segments were incubated with a cyclooxygenase inhibitor. indomethacin (INDO). These results suggest that prostanoids may be involved in the regulation o f AChE activity in pig airways. mtylchdimstcmse / butyrykhdinesterase / indomthacin / airways / epithelium
The Journal of pharmacology and experimental therapeutics, 1992
Human isolated intact pulmonary arterial muscle ring preparations which were precontracted with s... more Human isolated intact pulmonary arterial muscle ring preparations which were precontracted with serotonin (10 microM) relaxed when stimulated with low concentrations of histamine, 2-[2-thiazolyl]ethylamine or 2-[pyridyl]ethylamine (pD2 values: 8.66 +/- 0.22, 7.10 +/- 0.06 and 6.20 +/- 0.26, respectively) or contracted at higher concentrations of these agonists. This relaxant response was obliterated in endothelial denuded tissues. Chlorpheniramine (H1-antagonist; 0.25 and 2.5 microM) induced a small contractile response in the tissues at resting tone (0.08 +/- 0.03 g and 0.10 +/- 0.10 g, respectively). Chlorpheniramine also shifted the histamine relaxation curves to the right (pD2 values: control, 8.85 +/- 0.31; 0.25 microM, 6.90 +/- 0.41; and 2.5 microM, 5.58 +/- 0.30; N = 6). Dimaprit (H2-agonist) induced a small relaxation (20%) in both intact and denuded tissues. Treatment of the tissues with cimetidine (H2-antagonist; 50 microM), burimamide (H2/H3-antagonist; 10 microM) and imp...
Background Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular... more Background Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular disease. Endothelial repair plays a key role in the development of atherosclerosis. The objective was to examine associations between TL and proliferative dynamics of endothelial colony‐forming cells (ECFCs), which behave as progenitor cells displaying endothelial repair activity. Methods and Results To isolate ECFCs, we performed a clonogenic assay on blood samples from 116 participants (aged 24–94 years) in the TELARTA (Telomere in Arterial Aging) cohort study. We detected no ECFC clones in 29 (group 1), clones with no replating capacity in other 29 (group 2), and clones with replating capacity in the additional 58 (group 3). Leukocyte TL was measured by Southern blotting and ECFCs (ECFC‐TL). Age‐ and sex‐adjusted leukocyte TL (mean±SEM) was the shortest in group 1 (6.51±0.13 kb), longer in group 2 (6.69±0.13 kb), and the longest in group 3 (6.78±0.09 kb) ( P <0.05). In group 3, EC...
The prevalence and the prognostic role of orthostatic hypertension (OHyperT) in a very elderly po... more The prevalence and the prognostic role of orthostatic hypertension (OHyperT) in a very elderly population remain unknown. We aimed to investigate the association of OHyperT with cardiovascular morbidity and mortality in a population of elderly institutionalized patients. A longitudinal study with 2-year follow-up was conducted on 972 very elderly individuals (mean age [SD] 88[5]) living in nursing homes (223 men) that were able to maintain standing position, included in the PARTAGE study. Socio-demographic characteristics, medical history, chronic diseases (cardiovascular, central nervous system and respiratory), history of falls, comorbidity and medication use were collected. In addition, clinical examination of functional status, cognitive function, blood pressure (BP) and aortic stiffness was performed. BP measurements were repeated at 1 and 3 minutes after standing position. OHyperT was defined as an increase in SBP &amp;amp;gt;20mmHg during the 3 first minutes of standing up. Orthostatic hypotension (OH) was defined as a decrease in systolic BP (SBP) &amp;amp;gt;20mmHg and/or in diastolic BP (DBP) &amp;amp;gt;10mmHg. Cardiovascular morbid-mortality included nonfatal cardiovascular events leading to hospitalization or a specific long-term new treatment as well as death from cardiac, cerebrovascular, and other vascular causes. The population was divided into 3 groups: orthostatic normotension (ONT)(n = 540), OH(n = 157), and OHyperT(n = 275) groups. Mean age was similar and women were 82% in OHyperT versus 69% in OH group. At inclusion, all comorbidities but peripheral arterial disease (11% in OH versus 5% in OHT) were similarly distributed in the three groups. Sitting SBP was higher in OH compared to ONT and OHyperT groups (146[23],136[21],136[20] mmHg respectively, all P &amp;amp;lt; 0.001). OHyperT was associated with an increased risk of cardiovascular morbi-mortality adjusted (age and gender) risk-ratio [95% CL] (1.53[1.12-2.08]) compared to ONT. Adjusted (age and gender) risk-ratio of OH versus ONT was directionally increased (1.40[0.96-2.05]). Kaplan-Mayer curves (figure) for cardiovascular morbi-mortality show that ONT group presented higher survival than both OH (HR 1.44[0.95-2.17], P = 0.057) and OHyperT (HR 1.51[1.09-2.08], P &amp;amp;lt; 0.01). In a very old frail institutionalized population, increase in SBP by &amp;amp;gt;20mmHg in upright position has a negative prognostic impact on cardiovascular morbi-mortality.(Figure is included in full-text article.).
extensive laboratory investigations, no other etiologic factor could be detected. The rapid BP ri... more extensive laboratory investigations, no other etiologic factor could be detected. The rapid BP rise suggested sympathetic nervous system activation. Polydipsia is frequently associated with electrolyte distrubances but pathologic BP oscillations are exceptional. Based on a review of the literature, we discuss abnormal renal volume control and an impaired central BP regulation and barorefl ex function after brain stem infarction to explain the association of polydipsia with recurrent diurnal hypertension. Conclusions: Chronic polydipsia may be rare. However, it may occasionally represent a modifi able cause of BP elevations and treatment resistance in elderly patients particularly when volume handling is impaired by comorbidity.
Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury, 1993
While the selective peptido-LT-antagonists ICI 198615 and MK 571 block the LT contractions in bro... more While the selective peptido-LT-antagonists ICI 198615 and MK 571 block the LT contractions in bronchial tissues they do not inhibit the vascular responses. These results suggest that more than one leukotriene receptor exists in man. One type is present on human airways (LT-1) and is inhibited by potent antagonists. A second type (LT-2) is present on the pulmonary veins and is resistant to these compounds. Unlike IC1198615 and MK571, LTE4 and BAY u9773 (LT-analog) antagonized LT-induced contractions on the human pulmonary veins. The clinical effect of antagonizing this second peptido-LT receptor type has yet to be assessed.
The Journal of pharmacology and experimental therapeutics, 1987
A fixed concentration of paf-acether (platelet-activating factor; 4 microM) relaxed isolated guin... more A fixed concentration of paf-acether (platelet-activating factor; 4 microM) relaxed isolated guinea pig tracheal preparations which had been contracted with histamine (50 microM), serotonin (1 microM) or leukotriene D4 (0.1 microM). The relaxations were approximately 43, 100 and 57%, respectively. We did not observe any relaxant effect of paf-acether (4 microM) in tissues contracted with acetylcholine (50 microM). Both lyso paf-acether (10 microM) and bovine serum albumin (25 micrograms/ml) were without effect on histamine-contracted preparations. In the presence of indomethacin (1.7 microM; 30 min) or aspirin (0.1 mM; 30 min) the relaxant effect of paf-acether (4 microM) in tissues contracted with histamine was significantly reduced to approximately 10 and 12%, respectively. When paf-acether (4 microM) was added to histamine-contracted tracheal preparations in the presence of noradrenaline (0.1 microM) or prostaglandin E2 (PGE2, 10 nM) the relaxations were 62 and 82%, respectively....
The Journal of pharmacology and experimental therapeutics, 1992
Leukotrienes (LT) are potent spasmogenic agents in human isolated bronchial and pulmonary venous ... more Leukotrienes (LT) are potent spasmogenic agents in human isolated bronchial and pulmonary venous muscle preparations. Treatment of human isolated pulmonary veins with the L-serine borate complex (45 mM; 30 min) did not alter the LTC4 pD2 values in these preparations. The cysteinyl LT antagonists, ICI 198615, MK 571 and SKF 104353, significantly shifted to the right the LT concentration-effect curves in airways with pKB values against LTC4 of 8.4 for ICI 198615, 8.6 for MK 571 and 8.0 for SKF 104353. Similar results were found against LTD4. In contrast, these antagonists did not inhibit the LTC4 and LTD4 contractions in human pulmonary veins. LTE4 was a partial agonist on the human pulmonary veins and blocked the contractions with a pKp value of 6.3 against LTD4 and 6.6 against LTC4. An LT analog, BAY u9773, also blocked the LT contractions in bronchial and venous muscle preparations with pKp values against LTD4 and LTC4 of 6.5 and 6.7, respectively. These data provide pharmacologica...
The authors and the publisher have exerted every effort to ensure that drug selection and dosage ... more The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indica tions and dosage and for added warnings and precau tions. This is particularly important when the recom mended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopy ing, recording, microcopying, or by any information stor age and retrieval system, without permission in writing from the publisher or. in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center (see 'Information for Readers and Subscribers').
The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylc... more The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied. Epithelium removal caused a significant leftward shift of the acetylcholine concentration-effect curve, pD2 values were 2.86 +/- 0.11 and 3.34 +/- 0.18 for intact and rubbed tissue, respectively (P &lt; 0.05). However, there was no change in the acetylcholine maximal response. The sensitivity and responsiveness of the bovine bronchus to the other spasmogens were not significantly altered by removal of the epithelium. These results suggest that the epithelium of bovine bronchi modulates only acetylcholine-induced contraction.
-Acetylcholinesterase (AChE. EC 3. I. I .7) and butyrylcholinesterase (BChE. EC 3. I. I .8) activ... more -Acetylcholinesterase (AChE. EC 3. I. I .7) and butyrylcholinesterase (BChE. EC 3. I. I .8) activities were detected in bmnchial and bronchial epithelial cell homogenates o f the pig. In the bronchial homogenates. the maximal upstroke velocity (V,) o f AChE and the maximal velocity after second substrate fixation (V,) o f BChE were 5.70 i 0.46 and 7.87 i 0.81 mU/mg protein. respectively. In the epithelial cell homogenates. a smaller amount of cholinestcrase (ChE) was found: V , was 0.62 i 0.29 and V, was 1.56 i 0.33 mU/mg protein for AChE and BChE, respectively. AChE activity was increased by 21 i 5% in the bronchial homogenates and by 54 i 14% i n the epithelial cell homogenates. when intact bronchial segments were incubated with a cyclooxygenase inhibitor. indomethacin (INDO). These results suggest that prostanoids may be involved in the regulation o f AChE activity in pig airways. mtylchdimstcmse / butyrykhdinesterase / indomthacin / airways / epithelium
The Journal of pharmacology and experimental therapeutics, 1992
Human isolated intact pulmonary arterial muscle ring preparations which were precontracted with s... more Human isolated intact pulmonary arterial muscle ring preparations which were precontracted with serotonin (10 microM) relaxed when stimulated with low concentrations of histamine, 2-[2-thiazolyl]ethylamine or 2-[pyridyl]ethylamine (pD2 values: 8.66 +/- 0.22, 7.10 +/- 0.06 and 6.20 +/- 0.26, respectively) or contracted at higher concentrations of these agonists. This relaxant response was obliterated in endothelial denuded tissues. Chlorpheniramine (H1-antagonist; 0.25 and 2.5 microM) induced a small contractile response in the tissues at resting tone (0.08 +/- 0.03 g and 0.10 +/- 0.10 g, respectively). Chlorpheniramine also shifted the histamine relaxation curves to the right (pD2 values: control, 8.85 +/- 0.31; 0.25 microM, 6.90 +/- 0.41; and 2.5 microM, 5.58 +/- 0.30; N = 6). Dimaprit (H2-agonist) induced a small relaxation (20%) in both intact and denuded tissues. Treatment of the tissues with cimetidine (H2-antagonist; 50 microM), burimamide (H2/H3-antagonist; 10 microM) and imp...
Background Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular... more Background Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular disease. Endothelial repair plays a key role in the development of atherosclerosis. The objective was to examine associations between TL and proliferative dynamics of endothelial colony‐forming cells (ECFCs), which behave as progenitor cells displaying endothelial repair activity. Methods and Results To isolate ECFCs, we performed a clonogenic assay on blood samples from 116 participants (aged 24–94 years) in the TELARTA (Telomere in Arterial Aging) cohort study. We detected no ECFC clones in 29 (group 1), clones with no replating capacity in other 29 (group 2), and clones with replating capacity in the additional 58 (group 3). Leukocyte TL was measured by Southern blotting and ECFCs (ECFC‐TL). Age‐ and sex‐adjusted leukocyte TL (mean±SEM) was the shortest in group 1 (6.51±0.13 kb), longer in group 2 (6.69±0.13 kb), and the longest in group 3 (6.78±0.09 kb) ( P <0.05). In group 3, EC...
The prevalence and the prognostic role of orthostatic hypertension (OHyperT) in a very elderly po... more The prevalence and the prognostic role of orthostatic hypertension (OHyperT) in a very elderly population remain unknown. We aimed to investigate the association of OHyperT with cardiovascular morbidity and mortality in a population of elderly institutionalized patients. A longitudinal study with 2-year follow-up was conducted on 972 very elderly individuals (mean age [SD] 88[5]) living in nursing homes (223 men) that were able to maintain standing position, included in the PARTAGE study. Socio-demographic characteristics, medical history, chronic diseases (cardiovascular, central nervous system and respiratory), history of falls, comorbidity and medication use were collected. In addition, clinical examination of functional status, cognitive function, blood pressure (BP) and aortic stiffness was performed. BP measurements were repeated at 1 and 3 minutes after standing position. OHyperT was defined as an increase in SBP &amp;amp;gt;20mmHg during the 3 first minutes of standing up. Orthostatic hypotension (OH) was defined as a decrease in systolic BP (SBP) &amp;amp;gt;20mmHg and/or in diastolic BP (DBP) &amp;amp;gt;10mmHg. Cardiovascular morbid-mortality included nonfatal cardiovascular events leading to hospitalization or a specific long-term new treatment as well as death from cardiac, cerebrovascular, and other vascular causes. The population was divided into 3 groups: orthostatic normotension (ONT)(n = 540), OH(n = 157), and OHyperT(n = 275) groups. Mean age was similar and women were 82% in OHyperT versus 69% in OH group. At inclusion, all comorbidities but peripheral arterial disease (11% in OH versus 5% in OHT) were similarly distributed in the three groups. Sitting SBP was higher in OH compared to ONT and OHyperT groups (146[23],136[21],136[20] mmHg respectively, all P &amp;amp;lt; 0.001). OHyperT was associated with an increased risk of cardiovascular morbi-mortality adjusted (age and gender) risk-ratio [95% CL] (1.53[1.12-2.08]) compared to ONT. Adjusted (age and gender) risk-ratio of OH versus ONT was directionally increased (1.40[0.96-2.05]). Kaplan-Mayer curves (figure) for cardiovascular morbi-mortality show that ONT group presented higher survival than both OH (HR 1.44[0.95-2.17], P = 0.057) and OHyperT (HR 1.51[1.09-2.08], P &amp;amp;lt; 0.01). In a very old frail institutionalized population, increase in SBP by &amp;amp;gt;20mmHg in upright position has a negative prognostic impact on cardiovascular morbi-mortality.(Figure is included in full-text article.).
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