Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.

Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia.

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.

Involvement of ANF in the acute antidiuresis during PEEP ventilation.

To investigate the potential role of natriuretic factor (ANF) on changes on renal excretory function in response to increased intrathoracic pressure, seven patients were studied during three successive 60-min periods of 1) mechanical ventilation (MV) and zero end-expiratory pressure (ZEEP), 2) MV with 12 cmH2O positive end-expiratory pressure (PEEP), and 3) MV with the same level of PEEP while lower-body positive pressure (LBPP) was applied to restore venous return and increase central blood volume without fluid loading. Hemodynamics, renal excretory function parameters, and plasma immunoreactive atrial natriuretic factor (irANF) levels were recorded at the end of each period. Compared with ZEEP, PEEP induced a significant reduction of diuresis (from 134 +/- 17 to 59 +/- 13 ml/h, P less than 0.

The effects of urapidil therapy on hemodynamics and gas exchange in exercising patients with chronic obstructive pulmonary disease and pulmonary hypertension.

To examine the hemodynamic changes induced by vasodilator therapy with urapidil during exercise in patients with chronic obstructive pulmonary disease (COPD) and their potential impact on symptom-limited maximal oxygen consumption, we studied 12 clinically stable patients using a randomized, crossover design. Placebo or urapidil (60 mg orally thrice a day) was given during 48 h preceding each incremental maximal exercise testing. Urapidil compared to placebo consistently lowered the pulmonary artery pressure either at rest from 29 +/- 2.

Effects of indomethacin on pulmonary hemodynamics and gas exchange in patients with pulmonary artery hypertension, interference with hydralazine.

To assess the ability of indomethacin (Indo) to influence pulmonary vascular tone in patients with chronic lung disease, we studied the hemodynamic and gas exchange alterations induced by a 50-mg indomethacin infusion in 10 patients suffering from varying degrees of pulmonary artery hypertension and hypoxemia. The most pronounced effects were observed 3 h after Indo administration. Mean systemic arterial pressure (Psa) increased from 76 +/- 4 to 86 +/- 4 mm Hg (p less than 0.

Atrial natriuretic peptide concentrations and pulmonary hemodynamics in patients with pulmonary artery hypertension.

To define the relationship between plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) and hemodynamic parameters in patients with chronic pulmonary artery hypertension, we measured plasma concentrations of the peptide in 15 patients during right heart catheterization. Eleven patients had chronic obstructive pulmonary disease and 4 had pulmonary vascular disease of diverse etiology. At rest, plasma concentrations of IR-ANP positively correlated with mean pulmonary artery pressure (r = 0.

Antagonists of PAF-acether do not suppress thrombin-induced aggregation of ADP-deprived and aspirin-treated human platelets.

Four chemically distinct PAF-acether antagonists were used to test the hypothesis that the cyclooxygenase and ADP-independent thrombin-induced aggregation of human platelets is due to PAF-acether. The compounds 48740 RP, CV-3988, BN 52021 and Ro 19-3704 inhibited aggregation by PAF-acether whereas 48740 RP also interfered with aggregation by arachidonic acid, U 46619, collagen and thrombin. Aspirin-treated platelets aggregated in response to PAF-acether and to 0.

Plasmin: a possible physiological modulator of the human platelet adenylate cyclase system.

Plasmin was recently reported to inhibit platelet aggregation. We report here on the interaction of plasmin with the adenylate cyclase system of human platelets. Human plasmin caused a dose- and time-dependent increase in adenylate cyclase activity when added to a crude platelet membrane preparation.

Hemodynamic effects of urapidil in patients with pulmonary hypertension. A comparative study with hydralazine.

Vasodilator therapy for pulmonary hypertension ideally should cause a proportionately greater reduction of resistance in the pulmonary vascular bed than in the systemic circulation. This should limit the occurrence of systemic hypotension, which can complicate the use of most vasodilator drugs. Urapidil is a new vasodilator that acts by postsynaptic alpha 1-blockade while inhibiting the aortic pressure baroreceptor reflex and reducing central sympathetic tone.

Low molecular weight heparin fractions as an alternative therapy in heparin-induced thrombocytopenia.

Eight patients with a delayed-onset heparin-induced thrombocytopenia, with thrombotic complications requiring immediate anticoagulation in 7 of them, were given low molecular weight heparin (LMWH) fractions as alternative therapy. This treatment led to normalization of platelet count within 3-5 days in 6 patients with clinical recovery in 5. In 2 patients, thrombocytopenia persisted despite LMWH therapy.

Interference of the PAF-acether antagonist BN 52021 with endotoxin-induced hypotension in the guinea-pig.

Because of the potential role of PAF-acether in the pathogenesis of endotoxin shock, we examined the preventive and curative effects of BN 52021, a new PAF-acether antagonist in guinea-pig challenged with S. Typhimurium endotoxin. A biphasic reduction of mean arterial pressure was elicited by i.

[The adenylate cyclase system of human platelets].

This review summarizes current knowledge on the adenylate cyclase system of human platelets. In the first part, the main molecular entities of this system are described, emphasis being layed on coupling proteins (Ns, Ni) which transduce the hormonal message from receptors to the catalytic unit. The mechanisms by which regulation of adenylate cyclase occurs is discussed and a comprehensive model is proposed.

Cyclic nucleotide phosphodiesterase and aggregation in platelets from diabetic rats.

Platelet aggregation and cyclic nucleotide (cNCL) phosphodiesterase (PDE) have been studied in a new strain of insulin-dependent spontaneously diabetic rat (SDR). The rate of aggregation of washed platelets induced by ADP or ionophore A23187 was decreased in SDR as compared to asymptomatic littermates. The activity of soluble cGMP-PDE was increased in SDR, while no significant difference was observed between SDR and control in soluble and particulate cAMP-PDE activities nor in particulates cGMP-PDE activity.

Stimulation of rat platelet adenylate cyclase by an endogenous calcium-dependent protease-like activity.

The stimulation of adenylate cyclase by various exogenous proteases has been described in several tissues. In this study, we describe a 2 to 7-fold increase of adenylate cyclase activity in a particulate preparation from rat platelets following prior exposure of the homogenate to calcium. Calmodulin alone was unable to increase the adenylate cyclase activity and trifluoperazine only partially inhibited the calcium-dependent activation.