PubMed Health⌕ Search

Biomedical subjects

S Adnot

Publications and source records attributed to S Adnot.

118 records · Page 7Linked to original sources
PubMed1987

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. We investigated and compared the short-term effects of Urapidil and hydralazine in 10 patients suffering varying degrees of pulmonary hypertension. Each patient received either 0.35 mg/kg hydralazine or 0.75 mg/kg Urapidil intravenously on 2 sequential days in a randomized order. The main effect of Urapidil was to decrease the mean pulmonary artery pressure in all 10 patients from 44 +/- 4 to 37 +/- 3.5 mm Hg (p less than 0.001). After Urapidil infusion, the mean decrease of resistance in the pulmonary vascular bed (32%) exceeded that in the systemic circulation (25%). In contrast, pulmonary artery pressure remained unchanged with hydralazine, and predominant systemic vasodilation occurred: systemic vascular resistance decreased by 45%, whereas pulmonary vascular resistance decreased by 25%. Hydralazine markedly increased the cardiac index and induced tachycardia. Urapidil maintained the heart rate nearly constant and only slightly increased the cardiac index, thereby fostering the diastolic emptying of the pulmonary circulation. No significant change in arterial oxygenation occurred with either drug, although arterial oxygen partial pressure tended to increase with hydralazine. Urapidil may be a promising drug in the treatment of patients with pulmonary hypertension.

Aged↗
PubMed1986

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.v. endotoxin (300 micrograms/kg) in control animals, with a rapid drop of blood pressure (maximal decrease within 10 min), partial recovery at 20 min and a second gradual decrease after 30 min. Treatment with BN 52021 injected 15 min prior to endotoxin reduced the initial rapid drop of blood pressure from 38.5 +/- 5 mmHg in vehicle-treated controls (n = 15) to 17 +/- 3 mmHg (p less than 0.01) in animals treated with 1 mg/kg BN 52021(n = 10) and to 9.5 +/- 8 mmHg (p less than 0.01) in guinea-pigs treated with 6 mg/kg BN 52021 (n = 5). The early hypotensive phase was associated with severe thrombocytopenia-leukopenia; only the thrombocytopenia was reduced by BN 52021. The prolonged secondary phase of hypotension was reduced by BN 52021 pretreatment whereas a small increase of hematocrit persisted. The two phases of the arterial pressure profile during endotoxic shock were not observed in animals previously made thrombopenic by rabbit and anti-platelet serum and only the late hypotensive phase persisted. This late hypotension induced by endotoxin in thrombopenic animals was suppressed by BN 52021 pretreatment suggesting that BN 52021 may act via a platelet-independent mechanism. The intravenous injection of BN 52021 during the prolonged secondary phase of shock was followed by an immediate increase of the depressed blood pressure. This increase of blood pressure was dose-dependent, maximum at 6 mg/kg BN 52021, and observed in normal and thrombopenic animals. The interference of BN 52021 with endotoxin shock may be related to its PAF-acether antagonist properties and suggests that PAF-acether is an important participant in endotoxic shock.

Animals↗
PubMed1983

[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. In the second part, are reviewed the hormonal and non hormonal regulators of the adenylate cyclase system. The role of the platelet adenylate cyclase system is discussed in relation to pathology and the action of certain drugs on platelet activity.

Adenosine↗
PubMed1982

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. Furthermore, a kinetic study of soluble cGMP-PDE in platelets demonstrated that the apparent Km was lower while the Vmax was higher in SDR. Increases were also observed in the activities of particulate cAMP-PDE and cGMP-PDE at low and high substrate concentrations in liver and heart of SDR. These anomalies of platelet aggregation and cNCL-PDE in SDR were partially correctable by insulin. For comparison, a similar study was performed in streptozotocin-induced diabetic rats (STZ). In contrast to SDR, the rate of platelet aggregation induced by ADP was increased in STZ, and the activity of soluble cGMP-PDE in platelets was decreased in STZ. A similar decrease in the activities of cAMP-PDE in liver was also observed in STZ. This study confirms observations concerning the decrease of cGMP-PDE in tissues of STZ diabetic rats. However, since opposite anomalies in PDE activity as well as a platelet function were observed in another model of diabetes (SDR), the significance of these anomalies in the pathophysiology of diabetes requires further investigation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

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. On the other hand, calcium had a slight stimulatory effect on the particulate preparation but this activation was greatly enhanced by the addition of supernatant. Only the combined addition of calcium, supernatant and calmodulin to washed particulate preparations reconstituted the activation seen in homogenates. The activation was significantly inhibited by leupeptin and thiol reagents. It is concluded that platelets contain a calcium-dependent protease-like activity that is able to increase adenylate cyclase activity in membrane fractions. This phenomenon may be involved in the regulation of adenylate cyclase activity in platelets.

Adenylyl Cyclases↗