76 research outputs found
Semicarbazide-sensitive amine oxidase (SSAO): from cell to circulation
Semicarbazide-sensitive amine oxidase (SSAO) is a multi-functional enzyme
widely present in nature. It converts primary amines into their
corresponding aldehydes, while generating H(2)O(2) and NH(3). In mammals,
SSAO circulates in plasma, while a membrane-bound form (often referred to
as vascular adhesion protein-1, VAP-1) is found in many tissues and
organs, especially in adipocytes and vascular endothelial and smooth
muscle cells. In recent years, evidence has been accumulating that SSAO
has a role in protein cross-linking, formation of advanced glycation
end-products, atherogenesis, glucose regulation and leukocyte
extravasation at inflammation sites. Plasma SSAO is quite stable in
healthy adults, but is elevated in diabetes mellitus (both type 1 and type
2), congestive heart failure and liver cirrhosis. The origin of
circulating SSAO remains unclear, but recent evidence from clinical
studies and from (transgenic) animal studies suggests that adipocytes and
vascular endothelial cells may be the most important source. Studies with
cell cultures show evidence that the membrane-bound SSAO can be split off
from the cells, thus giving rise to the (truncated) circulating form of
SSAO. In some pathological conditions the diseased organ may be the main
source of the elevated plasma SSAO. Little is known as yet about the
regulation of plasma SSAO. Thyroid hormone appears to play a (modest) role
in this respect. Further evidence from clinical, animal and cell-culture
studies, helped by the new availability of selective SSAO inhibitors, is
needed to shed more light on the question of the regulation of SSAO
Sleep patterns in congenital dopamine beta-hydroxylase deficiency
Sleep patterns of two young female patients with congenital dopamine beta-hydroxylase deficiency are described. In this orthostatic syndrome central and peripheral noradrenergic failure occurs as a result of impaired beta-hydroxylation of dopamine. Consequently, the levels of dopamine and its metabolites are elevated. The relative importance of noradrenaline deficit in the face of dopamine excess for sleep-regulatory mechanisms can be inferred from the sleep pattern of these patients. No subjective sleep complaints were reported. The sleep patterns showed a high percentage of slow-wave sleep in both patients (29% and 34% of sleep period time) and a relatively low to normal percentage of REM sleep (18% and 21%). A normal cyclic REM sleep pattern was observed. Alpha-delta sleep occurred during light sleep (15% and 8%); consequently, the amount of stage 2 sleep was reduced. These results indicate that functional insufficiency of the noradrenergic system in two patients with dopamine beta-hydroxylase deficiency is not associated with profound changes in the (REM) sleep pattern. This supports a modulatory or permissive role for noradrenaline in REM sleep mechanisms
Comparison of N-terminal pro-atrial natriuretic peptide and atrial natriuretic peptide in human plasma as measured with commercially available radioimmunoassay kits
Atrial natriuretic peptide (ANP) has become an important parameter for assessing the condition of patients with cardia disease. Recently, attention has also focused on N-terminal pro-atrial natriuretic peptide (NtproANP) in this context. NtproANP circulates in plasma in higher concentration, is more stable ex vivo, and may be a better parameter for cardiac function over time. We have evaluated a new commercially available radioimmunoassay kit for NtproANP and compared results and method withthose of ANP measurements. The NtproANP kit was found to be reliable and easy to use (no plasma extraction step is necessary), with good reproducibility (coefficients of variation 7-15%). Normal values in 15 healthy laboratory workers, 25 healthy elderly subjects and 25 patients with heart failure were 207 ± 70, 368 ± 134 and 1206 ± 860 pmol/l, respectively, 8.3, 11.8 and 13.0 times higher, respectively, than corresponding ANP concentrations. NtproANP correlated well with ANP (r 0.64-0.78). We conclude that plasma NtproANP measurement may be a good alternative to plasma ANP measurement: technically, it is easier to perform, and NtproANP is more stable in plasma. Whether NtproANP is a better diagnostic and prognostic parameter than ANP remains to be further established
Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME
Experimental evidence indicates that the renal circulation is more
sensitive to the effects of nitric oxide (NO) synthesis inhibition than
other vascular beds. To explore whether in men the NO-mediated vasodilator
tone is greater in the renal than in the systemic circulation, the effects
of three different intravenous infusions of NG-nitro-L-arginine methyl
ester (L-NAME; 1, 5, and 25 microg. kg-1. min-1 for 30 min) or placebo on
mean arterial pressure (MAP), systemic vascular resistance (SVR), renal
blood flow (RBF), renal vascular resistance (RVR), glomerular filtration
rate (GFR), and fractional sodium and lithium excretion (FENa and FELi)
were studied in 12 healthy subjects, each receiving randomly two of the
four treatments on two different occasions. MAP was measured continuously
by means of the Finapres device, and stroke volume was calculated by a
model flow method. GFR and RBF were estimated from the clearances of
radiolabeled thalamate and hippuran. Systemic and renal hemodynamics were
followed for 2 h after start of infusions. During placebo, renal and
systemic hemodynamics and FENa and FELi remained stable. With the low and
intermediate L-NAME doses, maximal increments in SVR and RVR were similar:
20.4 +/- 19.6 and 23.5 +/- 16.0%, respectively, with the low dose and 31.4
+/- 26.7 and 31.2 +/- 14.4%, respectively, with the intermediate dose
(means +/- SD). With the high L-NAME dose, the increment in RVR was
greater than the increment in SVR. Despite a decrease in RBF, FENa and
FELi did not change with the low L-NAME dose, but they decreased by 31.2
+/- 11.0 and 20.2 +/- 6.3%, respectively, with the intermediate dose and
by 70.8 +/- 8.1 and 31.5 +/- 15.9% with the high L-NAME dose,
respectively. It is concluded that in men the renal circulation is not
more sensitive to the effects of NO synthesis inhibition than the systemic
circulation and that the threshold for NO synthesis inhibition to produce
antinatriuresis is higher than the threshold level to cause renal
vasoconstriction
Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock
BACKGROUND: The systemic hypotension during human sepsis has been ascribed
to increased production of nitric oxide (NO). Therefore, inhibitors of NO
synthesis have been used in the treatment of hypotension in patients with
septic shock. In addition, NO production may inhibit the synthesis and
vasoconstrictor effects of endothelin-1 (ET-1). In this study, we tested
whether ET-1 contributed to the vasopressor action of the NO synthase
inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in patients with
severe septic shock. METHODS AND RESULTS: Compared with healthy
volunteers, patients with septic shock had increased plasma levels of
nitrite/nitrate (37+/-5 [SEM] versus 12+/-5 mmol/L, P<0.01), the stable
end products of NO metabolism, and ET-1 (45+/-7 versus 3+/-2 pg/mL,
P<0.001). Plasma ET-1 concentration was not related to plasma
nitrite/nitrate concentration or blood pressure. Continuous infusion of
L-NAME (1 mg. kg-1. h-1 IV) for 12 hours increased mean arterial pressure
by 43+/-5% and systemic vascular resistance by 64+/-10% (both P<0.01). The
increase in blood pressure and systemic vascular resistance correlated
positively with the level of ET-1 (both P<0. 005) but not with plasma
nitrite/nitrate level. L-NAME infusion did not result in significant
changes in the plasma concentrations of ET-1 or nitrite/nitrate.
CONCLUSIONS: NO and ET-1 may both play a role in the cardiovascular
derangements of human sepsis. Although L-NAME does not increase ET-1
concentration in patients with septic shock, the vasopressor response
induced by L-NAME depends on the plasma level of ET-1. These findings may
indicate that inhibitors of NO synthesis unmask a tonic pressor response
of ET-1 in human septic shock
Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress
Dose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male volunteers participated in a placebo and a lorazepam session, during which the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.06, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). Heart rate showed a dose-dependent decrease during rest with an ED50 of 0.13 mg lorazepam, while lorazepam had no effect on the cardiovascular and plasma catecholamine response magnitudes to the CWT. Subjective fatigue and reaction time increased significantly after 0.94 mg lorazepam, while at the same dose vigor decreased; state anxiety after the CWT was not influenced by lorazepam. These data show differential effects of lorazepam on cardiovascular, biochemical and psychological function. While heart rate was suppressed at low doses during rest and reaction time and subjective fatigue increased at doses which induced sedation, state anxiety and physiological response patterns to the CWT were not influenced by lorazepam
ACE-versus chymase-dependent angiotensin II generation in human coronary arteries: a matter of efficiency?
OBJECTIVE: The objective of this study was to investigate ACE- and
chymase-dependent angiotensin I-to-II conversion in human coronary
arteries (HCAs). METHODS AND RESULTS: HCA rings were mounted in organ
baths, and concentration-response curves to angiotensin II, angiotensin I,
and the chymase-specific substrate Pro(11)-D-Ala(12)-angiotensin I
(PA-angiotensin I) were constructed. All angiotensins displayed similar
efficacy. For a given vasoconstriction, bath (but not interstitial)
angiotensin II during angiotensin I and PA-angiotensin I was lower than
during angiotensin II, indicating that interstitial (and not bath)
angiotensin II determines vasoconstriction. PA-angiotensin I increased
interstitial angiotensin II less efficiently than angiotensin I. Separate
inhibition of ACE (with captopril) and chymase (with C41 or chymostatin)
shifted the angiotensin I concentration-response curve approximately
5-fold to the right, whereas a 10-fold shift occurred during combined ACE
and chymase inhibition. Chymostatin, but not captopril and/or C41, reduced
bath angiotensin II and abolished PA-Ang I-induced vasoconstriction.
Perfused HCA segments, exposed luminally or adventitially to angiotensin
I, released angiotensin II into the luminal and adventitial fluid,
respectively, and this release was blocked by chymostatin. CONCLUSIONS:
Both ACE and chymase contribute to the generation of functionally active
angiotensin II in HCAs. However, because angiotensin II loss in the organ
bath is chymase-dependent, ACE-mediated conversion occurs more efficiently
(ie, closer to AT(1) receptors) than chymase-mediated conversion
Fatigue in primary Sjogren's syndrome
OBJECTIVE: To assess fatigue in relation to depression, blood pressure,
and plasma catecholamines in patients with primary Sjogren's syndrome
(SS), in comparison with healthy controls and patients with rheumatoid
arthritis. METHODS: For the assessment of fatigue the Multidimensional
Fatigue Inventory (MFI) was used, a 20 item questionnaire, covering the
following dimensions: general fatigue, physical fatigue, mental fatigue,
reduced motivation, and reduced activity. Furthermore, the Zung depression
scale was used to quantify aspects of depression. Forty nine female
primary SS patients, 44 female patients with rheumatoid arthritis (RA),
and 32 healthy women filled in both questionnaires. In addition, supine
values of blood pressure and plasma catecholamines were measured in the
patients with primary SS. RESULTS: Primary SS patients were more fatigued
compared with the healthy controls on all the five dimensions of the MFI.
When the analyses were repeated using depression as a covariate, group
differences disappeared for the dimensions of reduced motivation and
mental fatigue. In the primary SS patients, significant positive
correlations between depression and the dimensions of reduced motivation
and mental fatigue were found. Comparing patients with primary SS with
those with RA, using depression as covariate, no statistically significant
differences were found between these groups. No relation between fatigue
and blood pressure was found, but a negative correlation was observed
between the general fatigue subscale of the MFI and plasma noradrenaline.
CONCLUSION: Patients with primary SS report more fatigue than healthy
controls on all the dimensions of the MFI and when controlling for
depression significant differences remain on the dimensions of general
fatigue, physical fatigue, and reduced activity. The negative correlations
between levels of noradrenaline and general fatigue in patients with
primary SS may imply the involvement of the autonomic nervous system in
chronic fatigue
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