Biomedical subjects

A Carayon

Publications and source records attributed to A Carayon.

At least 37 records · Page 2Linked to original sources

PubMed1998

Acute effects of an endothelin-1 receptor antagonist bosentan at different stages of heart failure in conscious dogs.

OBJECTIVE: Inhibition by endothelin antagonist is a potential therapy in heart failure. However, the effect of endothelin inhibition during the development of heart failure has not been evaluated. The goal of our study was to examine the acute hemodynamic effects of the mixed endothelin receptor antagonist bosentan in the control state and at different stages of heart failure induced by right ventricular pacing (250 bpm) in conscious dogs. METHODS: Nine dogs were chronically instrumented for the measurements of left ventricular pressure and its first derivative (dP/dt), cardiac output, left ventricular regional wall thickness and aortic pressure. Bosentan (3 mg/kg, i.v. bolus) and placebo were given at control, at 1 week of pacing (stage of left ventricular dysfunction with perserved cardiac output) and at 3 weeks of pacing (phase of heart failure with low cardiac output). RESULTS: With the development of heart failure, baseline plasma endothelin level increased progressively. Placebo did not induce hemodynamic and plasma endothelin changes during the 30 min recording at any stage. At control, bosentan did not change hemodynamics. At 1 and 3 weeks of pacing, bosentan did not modify left ventricular myocardial function indices but reduced mean arterial pressure (by 7 +/- 2 and 8 +/- 1 mm Hg respectively, p < 0.005). Bosentan increased stroke volume at 3 weeks of pacing only. CONCLUSIONS: Endothelin inhibition by endothelin antagonist bosentan, decreases aortic pressure in both early left ventricular dysfunction and in heart failure in contrast with the control state. In the phase of heart failure with low cardiac output, bosentan increases stroke volume. In the early left ventricular dysfunction, bosentan, by reducing arterial pressure, may limit the deterioration of cardiac function through a reduction of the workload imposed on the heart.

Animals↗

PubMed1998

Effects of ANF infusion on the renal responses to lower-body negative pressure in humans.

To investigate the role of atrial natriuretic factor (ANF) in renal responses to a decrease in central blood volume, we examined the effects of ANF infusion on renal function and hormones during prolonged lower-body negative pressure (LBNP). Ten healthy volunteers participated in two experimental sequences, each comprising a 120-min baseline period followed by the application of -20 mm Hg LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p-aminohippuric acid clearance techniques. LBNP induced a significant decrease in ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5 ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p < 0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05), and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from 20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP with saline vehicle infusion, values obtained during LBNP with ANF infusion were similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112 +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p = 0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/- 0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87 +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the antinatriuretic effect of low-level LBNP and its PRA-increasing effects without altering renal hemodynamic responses to LBNP, although there is a decrease in the LBNP-induced forearm vasoconstriction. These results were obtained with plasma ANF levels slightly higher than those in baseline. They support the hypothesis that a decrease in ANF secretion might contribute to the antinatriuretic effect of LBNP.

Adult↗

PubMed1997

Endothelin-1 in the lungs of patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by an increase in vascular tone and an abnormal proliferation of muscle cells in the walls of pulmonary arteries. Recent studies have found high plasma endothelin-1 (ET-1) concentrations in patients with PH. This study was conducted to assess whether elevated circulating ET-1 levels in PH really reflect excessive local pulmonary production. METHODS: We prospectively studied ET-1 concentration in lung specimens from 6 control subjects and 13 patients with severe PH referred for lung or heart-lung transplantation (6 patients had primary PH and 7 PH secondary to congenital heart defect). Endothelin-like immunoreactivity (ET-LI) was measured in plasma and lung tissue, using a radioimmunoassay, after ET-1 extraction. Reverse-phase high-performance liquid chromatography was also performed. RESULTS: Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in controls (10.7 +/- 0.8 vs 5.3 +/- 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI was significantly higher in patients with PH, irrespective of its cause, than in controls (25.2 +/- 5.1 vs 8.1 +/- 1.1 pg/mg, P < 0.03). ET-LI pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 +/- 8.6 vs 22.8 +/- 5.4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-LI pulmonary concentrations and pulmonary vascular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immuno-reactivity was detected in the same fraction as ET-1. CONCLUSIONS: The striking increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascular abnormalities of pulmonary hypertension.

Adult↗

PubMed1997

Prognostic value of plasma endothelin-1 in patients with chronic heart failure.

AIMS: Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. METHODS AND RESULTS: Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001). CONCLUSION: Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Atrial Natriuretic Factor↗

PubMed1997

Angiotensin II-induced phosphoinositide production and atrial natriuretic peptide release in rat atrial tissue.

The effect of angiotensin II (Ang II) on inositol phosphate (IP) production and atrial natriuretic peptide (ANP) release was studied in sliced rat atrial tissue. The ability of Ang II (10(-7) M) to stimulate IP accumulation was detected after 1 min of incubation, and the maximal increase was observed at 5 min. In (2-3H) inositol-labeled atrial tissue, Ang II induced the formation of (2-3H) inositol monophosphate (IP1) in a dose-dependent manner. The effect of Ang II (10(-7) M) on IP1 was prevented by losartan (10(-7) M) but was not affected by PD123319 (10(-7) M). Similar effects were observed on Ang II-induced ANP release in the presence of these antagonists. The mechanism of ANP liberation induced by this peptide was independent of cyclic adenosine monophosphate (cAMP) and regulated by nitric oxide (NO). The role of Ca2+ in the effect of Ang II was tested by 1,2-bis (o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM; 10(-5) M), a chelator of intracellular Ca2+ that prevented the release of ANP by Ang II stimulation. We concluded that Ang II induced IP production and ANP release through AT1 receptors. Stimulation of ANP release by Ang II was dependent on intracellular Ca2+.

Angiotensin II↗

PubMed1997

Hemodynamic and neurohormonal effects of flosequinan in patients with heart failure.

In a double-blind, placebo-controlled study, the central and peripheral hemodynamic effects of 100 mg oral flosequinan and the impact of this drug on neurohormonal activation were noninvasively evaluated in 18 patients with congestive heart failure, after the first administration and after 10 days of treatment. No significant hemodynamic and neurohormonal changes were observed after acute administration. After 10 days, flosequinan produced central and peripheral hemodynamic improvement characterized by an increase in left ventricular circumferential fiber shortening velocity (+12%), a decrease in total systemic resistance (-36%), and an increase in leg blood flow (+37%). No significant changes were observed in heart rate and arterial pressure in patients receiving flosequinan, though a slight increase in heart rate (+17%) was recorded. Despite these favorable hemodynamic effects, flosequinan significantly increased plasma norepinephrine (+38%) and plasma renin activity (+13%) after 10 days of treatment. Thus, the beneficial central and peripheral hemodynamic effects of flosequinan are accompanied by activation of the sympathetic and reninangiotensin systems. This might be related to the unfavorable effects of the drug on survival in patients with heart failure.

Adult↗

PubMed1997

Renal and vascular effects of C-type and atrial natriuretic peptides in humans.

C-type natriuretic peptide (CNP) may affect renal and vascular functions differently from atrial natriuretic peptide (ANP). The objective of this study was to compare the renal and vascular actions of CNP to those of ANP in normal men. CNP or ANP (0.005, 0.01, and 0.05 microg x kg(-1) x min(-1)) were given by infusion to eight healthy volunteers. CNP caused dose-dependent increases in natriuresis (U(Na)) and in the fractional excretion of sodium (FE(Na)) with no effect on diuresis (UV), renal plasma flow, and glomerular filtration rate (GFR). Fraction of filtration (FF) increased only with the 0.05 microg x kg(-1) x min(-1) CNP dose. ANP caused larger increases in U(Na), FE(Na), and FF than CNP and also increased UV at 0.01 and 0.05 microg x kg(-1) x min(-1) and GFR at 0.05 microg x kg(-1) x min(-1). Although the ANP and CNP infusions produced similar elevation in the respective peptides plasma levels, urinary and nephrogenous guanosine 3',5'-cyclic monophosphate increased less in response to CNP than to ANP. Blood pressure, forearm blood flow, plasma renin activity, and aldosterone remained unaffected during the peptides infusion. Plasma ANP increased slightly during CNP infusion. Our data indicate a higher threshold of renal response to CNP than to ANP. In contrast to ANP, CNP probably may not act as an endocrine factor in humans.

Adult↗

PubMed1996

Captopril does not acutely modulate plasma endothelin-1 concentration in human congestive heart failure.

Congestive heart failure (CHF) is a syndrome characterized by increased levels of angiotensin II (Ang II) and endothelin-1 (ET-1). In vitro, Ang II stimulates ET-1 release. The purpose of the study was to assess the effect of a single dose of an angiotensin-converting enzyme inhibitor (ACEI) captopril versus placebo on plasma endothelin concentration in human congestive heart failure. Captopril (25 mg, given orally) was compared with placebo in a group of 20 patients with systolic dysfunction in a double-blind randomized study. Plasma irET concentration was significantly increased in CHF patients compared with normal subjects (5.59 pg/ml +/- 0.35 vs. 3.58 pg/ml +/- 0.99, p < 0.0002). Despite the decrease in systolic blood pressure and the increase in plasma renin activity, suggesting a significant blockade of the renin-angiotensin system, no difference in plasma irET-1 was observed between captopril and placebo. Our results suggest that captopril does not acutely influence irET-1 plasma concentration in human CHF. These data do not support the hypothesis that the acute vasodilator effect of a single dose of 25 mg of captopril given daily orally involves modulation of the increased plasma concentration of endothelin observed in CHF.

Adult↗

PubMed1996

Decrease in internal jugular endothelin levels after carotid cross-clamping during human carotid revascularization procedures.

Endothelin-1 (ETL-1), a peptide recently isolated from vascular endothelial cells, acts in cerebral arteries in vitro as a potent and long-lasting vasoconstrictor and has been implicated in the development of cerebral vasospasm. To ascertain whether this new vasoconstrictor has any effect on regulation of the cerebral circulation, we measured plasma ETL-1 concentrations in patients undergoing carotid revascularization and attempted to correlate the variations of venous and arterial plasma ETL-1 with the characteristics of the procedure, including cerebral vasospasm. We prospectively studied 11 patients undergoing a total of 14 carotid surgical revascularization procedures (12 endarterectomies, 2 polytetrafluoroethylene bypass grafts from the common to the internal carotid arteries). Before carotid cross-clamping, blood samples were drawn from the internal jugular vein and the healthy common carotid artery proximal to the occlusive lesion to be treated. After endarterectomy, blood samples were withdrawn from the internal, external, and common carotid arteries. After the release of the last clamp, a final aliquot of blood was withdrawn from the internal jugular vein. After plasma extraction on a C2-ethyl microcolumn, plasma endothelin-like immunoreactivity was measured by means of radioimmunoassay with a polyclonal antibody. In 9 of the 11 patients, internal jugular vein ETL-1 concentration decreased statistically significantly after carotid artery cross-clamping (4.2 +/- 1.4 pg/ml vs. 3.9 +/- 1.1 pg/ml; p < 0.05). In the 2 patients in whom ETL-1 levels failed to drop, a shunt was used during the procedure in 1, and the other was the only patient who had an ipsilateral ischemic postoperative stroke. The decrease in internal jugular vein ETL-1 concentration failed to correlate with any of the cross-clamping times. The level of arterial blood ETL-1 remained steady in the common carotid artery before and after cross-clamping (4.5 +/- 1.5 pg/ml vs. 4.6 +/- 0.9 pg/ml). A small, nonsignificant decrease in ETL-1 level was noted in the external and internal carotid arteries after cross-clamping. The decrease in internal jugular vein ETL-1 levels may in part reflect a compensatory response to carotid artery cross-clamping, which could limit the reduction of local cerebral blood flow.

Blood Vessel Prosthesis↗

PubMed1996

Cellular mechanism of angiotensin II-induced atrial natriuretic peptide release in rat right atrial tissue.

This study presents an investigation of the mechanism of angiotensin II (Ang II)-induced atrial natriuretic peptide (ANP) release in superfused sliced right atria of rats. Ang II (0.1 microM) enhanced ANP release by 49%. This phenomenon was significantly blocked by (Sara1-Ileu 8) Ang II (1 microM) and losartan (0.1 microM). The use of neomycin (100 microM), a phospholipase-C inhibitor completely suppressed the effect of Ang II on ANP increase. To elucidate the intracellular mechanism of ANP released by Ang II, the role of protein kinase C (PKC) was determined by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and phorbol ester : 4-beta-phorbol 12-myristate-13-acetate (PMA). We observed that PMA (0.1 microM) stimulated ANP release whereas H-7 (10 microM), an inhibitor of PKC in the presence of Ang II, prevented ANP increase. The role of calcium was also evaluated with 8-(N-N-diethylamino)-ocytyl-3,4,5, trimethoxy-benzoate (TMB-8) (10 microM) and N-(6-aminohexyl)-5-chloro-1-naphtalene sulfonamide (W-7) (10 microM), which completely inhibited ANP release by Ang II. Pre-treatment with diltiazem (10 microM), an antagonist of the Ca++ channel, did not prevent ANP increase due to Ang II, but A23187 (5 microM) enhanced ANP release by Ang II. These results suggest that PKC and intracellular calcium play an important role in ANP release under the influence of Ang II in rat atrial tissue.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1996

Acute and long-term dose-response study of quinapril on hormonal profile and tissue angiotensin-converting enzyme in Wistar rats.

Therapeutic response to angiotensin-converting enzyme (ACE) inhibitors was reported to be better related to tissular than to circulating levels of ACE inhibition, especially during chronic therapy. We studied the relations between plasma concentrations of angiotensin I (AI), plasma renin activity (PRA), angiotensin II (AII), and aldosterone (by radioimmunoassay, RIA) and levels of serum and tissue ACE activities during acute and chronic quinapril administration in rats. Forty-eight male Wistar rats received quinapril by gavage for either 1 day (n = 24) or 15 days (n = 24) at different doses (control, 0.1, 1, and 10 mg/kg/day; 6 rats at each dose). Plasma hormonal parameters, serum, and tissue (lung, heart, and aorta) ACE activities were measured 3 h after the last gavage. Significant dose-dependent inhibitions of serum and lung ACE during acute and chronic treatments were observed (p < 0.05). Degrees of serum and heart ACE inhibition (at 0.1 mg/kg/day) were significantly lower with chronic than with acute treatment (p < 0.05). Degree of inhibition in lung, which represents the main source of total ACE, was similar during acute and chronic treatments. Among plasma hormonal parameters, plasma AI was correlated to PRA and showed the best correlation with ACE inhibition. After logarithmic transformation, log AI was significantly correlated to ACE activity in lung during chronic treatment (r = -0.85, p < 0.05). This parameter may provide a useful index for ACE inhibitor dosage adjustment during chronic therapy.

Aldosterone↗

PubMed1996

Plasma levels and molecular forms of proatrial natriuretic peptides in healthy subjects and in patients with congestive heart failure.

A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1-30). Plasma concentrations of proANP(1-30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1-30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1-30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1-30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1-30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP.

Adult↗

PubMed1995

Blood and peritoneal levels of endothelin in continuous ambulatory peritoneal dialysis patients.

We have determined the plasma levels of endothelin-1 (ET-1) in patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis (CAPD). In 10 CAPD patients mean plasma ET levels (7.01 +/- 0.5 pg/ml) were found higher than in normal subjects (3.6 +/- 0.6 pg/ml). Peritoneal clearance of ET-1 was 1.58 +/- 0.12 ml/min and 2.3 +/- 0.2 ml/min during an isotonic peritoneal exchange and a hypertonic exchange, respectively. Plasma ET-1 levels decreased slightly but significantly during a hypertonic 4-hour exchange (from 7.01 +/- 0.5 to 6.14 +/- 0.4 pg/ml) (p < 0.05) and were not modified by an isotonic 4-hour exchange (from 5.7 +/- 0.5 to 6.4 +/- 0.4 pg/ml). ET-1 is known to be an important vascular stimulant and thus elevated ET-1 levels may play a role in the genesis of cardiovascular complications which are the leading cause of mortality in these patients.

Aged↗

PubMed1995

Myocardial production of prostaglandins: its role in atrial natriuretic peptide release.

In recent years, considerable evidence has been accumulated on prostaglandins (PG) in modulating atrial natriuretic peptide (ANP) release. In the current study we investigated whether eicosanoids promote isoproterenol-induced ANP secretion from superfused rabbit sliced atria. Inclusion of the cyclooxygenase inhibitor indomethacin (10 mumol) to the superfusing medium abolished isoproterenol-induced ANP release. Next, PGE2, but not PGF2 alpha or PGI2 (10 mumol), increased ANP release. Furthermore, isoproterenol-induced PGE2 formation was fully attenuated by indomethacin. Dibutyl-cAMP (0.5 mmol) had no effect on PGE2 formation, and the protein kinase A (PKA) inhibitor H89 (20 mumol) did not alter isoproterenol-induced PGE2 formation. On the other hand, indomethacin led to a significant decrease in isoproterenol-induced cAMP production. In addition, PGE2 enhanced basal cAMP concentration in superfusates. Superfusion of sliced atria by forskolin (10 mumol) or by dibutyl-cAMP (0.5 mmol) produced a significant rise in ANP release. Finally, H89 was ineffective on basal ANP release but abolished the increase of ANP release in response to isoproterenol or to PGE2. We conclude that: the effect of isoproterenol on ANP release is sensitive to indomethacin and H89; PGE2, but not PGE2 alpha or PGI2, increases ANP release; isoproterenol promotes myocardial PGE2 formation independently of adenylate cyclase and PKA activation pathways; and PGE2-induced ANP release is mediated by cAMP production and subsequent PKA activation. These results suggest that isoproterenol-induced ANP release appears to be mediated at least partly by PGE2 with underlying cAMP formation and PKA activation.

Animals↗

PubMed1995

Alterations in atrial natriuretic peptide gene expression during endurance training in rats.

Spontaneous and experimental rises of intracardiac pressure and/or volume increase the level of atrial natriuretic (ANP) mRNA in rat atrial tissue. There is expanding evidence that ANP synthesis is increased in the ventricle under such conditions. However, little is known with regard to the myocardial ANP synthesis response to physical training. In this study, plasma and atrial immunoreactive ANP concentrations were measured in Sprague-Dawley rats trained on a treadmill and compared to sedentary controls. Atrial natriuretic peptide mRNA was detected in the heart cavities of each group by dot-blot hybridization analysis. Physical training reduced the mean immunoreactive ANP plasma levels from 405 +/- 99 to 303 +/- 45 ng/l (p < 0.05). Immunoreactive ANP in the left atrium was depleted after endurance training, while immunoreactive ANP concentration in the right atrium was unaffected. Physical training resulted in a 70% (p < 0.01) rise in ANP mRNA of the right atrium, while no changes in the other compartments were found. These data indicate that during physical training: ANP mRNA does not increase in ventricles; despite depletion of immunoreactive ANP in the left atrium, no corresponding changes of ANP mRNA are detected; and ANP mRNA increases in the right atrium while its immunoreactive ANP does not. These findings suggest that during chronic exercise the ratio between immunoreactive ANP and ANP gene expression in the atria may be altered.

Animals↗

PubMed1995

Normal human polyspecific immunoglobulin G (intravenous immunoglobulin) modulates endothelial cell function in vitro.

We have analysed the in-vitro effect of pooled normal polyspecific immunoglobulin G (IVIg) and F(ab')2 fragments of IVIg on the secretion of prostacyclin (PGI2), thromboxane A2 (TxA2), and endothelin from cultured human umbilical vein endothelial cells. The stable metabolites, 6-keto-PGF1 alpha and TxB2, as well as endothelin, were measured by radioimmunoassay after extraction from the culture supernatants. IVIg inhibited TxB2 and endothelin secretion in a dose-dependent manner, but not that of 6-keto-PGF1 alpha. Therefore the ratio of 6-keto-PGF1 alpha/TxB2 increased (+600%). The effect of F(ab')2 fragments prepared from IVIg was similar to that observed with IVIg, indicating that the effect of IVIg was mediated by the variable region of immunoglobulin. The results suggest that part of the effects of IVIg in inflammatory vasculitis may be due to a modification of the PGI2/TxA2 ratio and inhibition of endothelin secretion, and that natural IgG antibodies may participate in the homeostatic process of endothelium under physiological conditions.

Cells, Cultured↗

PubMed1994

Effects of the calcium channel blockers, diltiazem and Ro 40-5967, on systemic haemodynamics and plasma noradrenaline levels in conscious dogs with pacing-induced heart failure.

1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in conscious dogs, the acute haemodynamic and sympathetic effects of diltiazem and Ro 40-5967 (a novel calcium channel blocker) in the control state and in heart failure. 3. Thirteen dogs were instrumented with a micromanometer and an aortic catheter. After completion of experiments in the control state, heart failure was induced by right ventricular pacing (250 beats min-1, 3 weeks). Diltiazem and Ro 40-5967 were given intravenously (0.8 mg kg-1 and 1.0 mg kg-1 respectively). Cardiac output was measured by a thermodilution technique. 4. In the control state, both agents decreased similarly mean aortic pressure with significant increases in heart rate, cardiac output (both +1.0 l min-1 and P < 0.001) and plasma noradrenaline (both +55%) without changes in left ventricular dP/dtmax. In heart failure, for matched decreases in mean aortic pressure, neither diltiazem nor Ro 40-5967 changed heart rate significantly; diltiazem decreased cardiac output (-0.3 l min-1, P < 0.02) and dP/dtmax (-14%, P < 0.001) while Ro 40-5967 still increased cardiac output (+0.3 l min-1, P < 0.02) although the increased amount was smaller than in the control state. Plasma noradrenaline level was increased more during diltiazem infusion (+120%) than during Ro 40-5967 infusion (+38%, P < 0.001). 5. Diltiazem and Ro 40-5967 have similar haemodynamic and sympathetic effects in the control state.Heart failure alters haemodynamic and sympathetic responses to both calcium channel blockers but the magnitude of the alteration appears to be different. Diltiazem exerts a depressant effect on cardiac function which cannot be overcome by its vasodilator effect and sympathetic stimulation, while Ro 40-5967 has little effect on cardiac function. These data suggest that novel calcium channel blockers with less depressant effect may not be detrimental in heart failure.

Animals↗

PubMed1994

Rapid development of nitrate tolerance in healthy volunteers: assessment using spectral analysis of short-term blood pressure and heart rate variability.

Nitrate tolerance is characterized by a loss of nitroglycerin (NTG) vasodilating and hypotensive effects during continuous administration, but is difficult to detect clinically. We hypothesized that the decrease in arterial blood pressure (BP) and the reflex sympathetic activation and tachycardia due to baroreflex deactivation associated with rapid intravenous (i.v.) infusion of NTG would be decreased during continuous NTG patch therapy as a result of tolerance to transdermal NTG. Sympathetic activation was measured as the change in amplitude of low-frequency (66-129 mHz) oscillations in BP and heart rate (HR) recorded by a noninvasive method. Eleven healthy male volunteers received rapid i.v. infusion of 0.45 mg NTG in 1 min on 3 consecutive days: before NTG patch, after 22.5 h of patch therapy, and 22.5 h after patch removal. The maximum decrease in systolic BP (SBP) and maximum reflex tachycardia as well as the sympathetic activation produced by i.v. NTG were compared during each of the three study periods. The maximum decrease in SBP was 38 +/- 8 mm Hg before NTG patch and 27 +/- 15 mm Hg during NTG patch (p < 0.05), with return to baseline values (37 +/- 13 mm Hg) after patch removal. There was no significant change in amplitude of reflex tachycardia among study periods. However, low-frequency oscillations in SBP increased by 40 +/- 31% in the absence of NTG patch and by only 9 +/- 35% after 22.5 h of patch therapy (p < 0.05). Patch removal resulted in a significant rebound increase in these oscillations (70 +/- 51%; p < 0.05 vs. baseline).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗