[Ureter drugs].

Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access.

Mixing rules for multicomponent mixture mass diffusion coefficients and thermal diffusion factors.

Mixing rules are derived for mass diffusion coefficient and thermal diffusion factor matrices by developing compatibility conditions between the fluid mixture equations obtained from nonequilibrium thermodynamics and Grad's 13-moment kinetic theory. The mixing rules are shown to be in terms of the species mole fractions and binary processes. In particular, the thermal diffusion factors for binary mixtures obtained by the Chapman-Enskog expansion procedure are suitably generalized for many-component mixtures.

[Synthesis of functionalized cyanines. Fluorescence properties following complexation of cations].

The ionophoric properties of podands containing dioxazaphosphocane moieties linked by inactive spacers were studied. To increase the detection sensibility of these compounds we introduced a cyanine as spacer. Fluorescence analysis demonstrated the interest of cyanines as active spacers since the complexation by cations as Ca2+ and Mg2+ gives an enhancement of the emission intensity.

Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion-induced necrosis and apoptosis in vivo.

Reperfusion of ischemic tissue results in the generation of reactive oxygen species that contribute to tissue injury. The sources of reactive oxygen species in reperfused tissue are not fully characterized. We hypothesized that the small GTPase Rac1 mediates the oxidative burst in reperfused tissue and thereby contributes to reperfusion injury.

Structure-activity analysis of the effects of lysophosphatidic acid on platelet aggregation.

Lysophosphatidic acid (1-acyl-sn-glycero-3-phosphate or LPA) is a phospholipid mediator displaying numerous and widespread biological activities and thought to act via G-protein-coupled receptors. Here we have studied the effects on human platelets of a number of LPA analogues, including two enantiomers of both N-palmitoyl-(L)-serine-3-phosphate ((L) and (D)NAPS for N-acyl-phosphoserine) and 2-(R)-N-palmitoyl-norleucinol-1-phosphate ((R) and (S)PNPA), cyclic analogues of 1-acyl-sn-glycero-3-phosphate (cPA) and of 1-O-hexadecyl-sn-glycero-3-phosphate (cAGP), sphingosine-1-phosphate (SPP), as well as two palmitoyl derivatives of dioxazaphosphocanes bearing either a P-H or a P-OH bond (DOXP-H and DOXP-OH, respectively). Nine of these compounds induced platelet aggregation with the following order of potency: SPP < cAGP < DOXP-OH < (L)NAPS = (D)NAPS < (R)PNPA = (S)PNPA < LPA < AGP, EC50 varying between 9.

Vasodilator responses to desmopressin and its diluent, chlorobutanol, in the hindquarters vascular bed of the cat.

Desmopressin is a synthetic analog of vasopressin used to promote hemostasis and reduce postoperative blood loss. Recent studies have shown that desmopressin decreases arterial blood pressure in the anesthetized rat and relaxes isolated segments of aorta and pulmonary artery. Responses to a clinical preparation of desmopressin were investigated in the hindquarters vascular bed of the cat under constant flow conditions so that changes in perfusion pressure directly reflect changes in vascular resistance.

Heparin treatment enhances the recovery of neoendothelial acetylcholine-induced vascular relaxation after balloon catheter injury in the rabbit aorta.

Background: After catheter injury, the neoendothelium that grows is abnormal in morphology and in acetylcholine-induced generation of endothelium-derived relaxing factor (EDRF). Heparin has been shown to have stimulatory effects on vascular endothelial growth in vitro. Its effect in vivo on neoendothelial cell morphology and metabolism after injury has not been described.

Angiopeptin enhances acetylcholine-induced relaxation and inhibits intimal hyperplasia after vascular injury.

The effects of the somatostatin analogue, angiopeptin (BIM-23014), on neoendothelial function, as evidenced by formation of prostaglandin (PG) I2 and by acetylcholine-induced relaxation (formation of endothelial-derived relaxing factor), were investigated in the rabbit aorta. A balloon catheter injury of the thoracic and abdominal aorta was induced in New Zealand White rabbits. Animals treated with angiopeptin for 2 or 4 wk were compared with untreated rabbits at 2 or 4 wk after the induction of injury, as well as to sham-operated controls.

Selective and complete blockade of acetylcholine-induced relaxation in rabbit aortic rings by N omega-nitro-L-arginine but not by glybenclamide.

This study addressed the possibility that acetylcholine-induced relaxation in the rabbit aorta is mediated by dual mechanisms: one N omega-nitro-L-arginine (NLA)-sensitive, the other glybenclamide-sensitive. Acetylcholine, nitroglycerin and BRL38227 (lemakalim), an activator of glybenclamide-sensitive potassium channels, were added to an organ bath containing rabbit aortic rings in a cumulative manner in the absence or presence of NLA and/or glybenclamide. NLA inhibited acetylcholine-induced relaxation and potentiated the relaxant response to nitroglycerin.

Analysis of the inhibitory effects of DuP 753 and EXP 3174 on responses to angiotensin II in the feline hindquarters vascular bed.

The effects of DuP 753 and EXP 3174, nonpeptide angiotensin II type 1 antagonists, on responses to angiotensin II were investigated in the hindquarters vascular bed of the cat. Under constant flow conditions, injections of angiotensin II into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Responses to the peptide were stable with respect to time, did not exhibit tachyphylaxis, and 2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)biph eny l-4-yl]methyl]methyl]imidazole (DuP 753) in doses of 1 and 2.

Penile erections induced by vasoactive intestinal peptide and sodium nitroprusside.

The use of vasoactive intestinal peptide (VIP), sodium nitroprusside (SNP), and the reference combination of papaverine, prostaglandin E1, and phentolamine was studied in 22 adult cats. The maximal erectile response (intracavernous pressure, penile length, and rigidity) was produced by intracavernous injection of a combination of 1.65 mg papaverine, 0.

Differential effects of nitric oxide synthesis inhibitors on vascular resistance and responses to acetylcholine in cats.

The effects of dose and the duration of treatment with N omega-nitro-L-arginine (L-NNA) and N omega-nitro-L-arginine methyl ester (L-NAME) on vascular resistance and the vasodilator response to acetylcholine (ACh) were investigated in the hindquarters vascular bed of the cat under constant flow conditions. L-NNA and L-NAME increase perfusion pressure and reduce vasodilator responses to ACh in the hindquarters vascular bed; however, the dose and time of exposure required to produce these effects are different. When L-NNA (2.

Analysis of responses to big endothelin in the hindquarters vascular bed of the cat.

Objective: To investigate vascular responses to the endothelin-1 (ET-1) precursor, human big endothelin 1-38 (big ET), in the peripheral vascular bed of the cat.

Design: These studies were designed to investigate the hypothesis that bit ET is converted to an active peptide with properties similar to ET-1.

Setting: Hindquarters vascular bed of the cat under conditions of controlled bloodflow; changes in perfusion pressure reflect changes in vascular resistance.

Analysis of pulmonary and systemic vascular responses to platelet-activating factor in the cat.

Pulmonary and systemic vascular responses to platelet-activating factor (PAF) were investigated in the anesthetized cat. Intravenous injections of PAF decreased arterial pressure, increased pulmonary arterial pressure, and caused small but significant decreases in right and left atrial pressures. A transient increase in cardiac output was followed by a secondary decrease, and heart rate was increased.

Comparison of responses to sarafotoxins 6a and 6c in pulmonary and systemic vascular beds.

Cardiovascular and pulmonary responses to sarafotoxin (S) 6a and S6c were investigated in the anesthetized cat. Intravenous injections of the peptides in doses of 0.1-1.

N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was elevated with U-46619, intralobar injections of acetylcholine, bradykinin, sodium nitroprusside, isoproterenol, prostaglandin E1 (PGE1), lemakalim, and 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intravenous administration of L-NAME elevated lobar arterial and systemic arterial pressures without altering left atrial pressure.

Influence of SQ 29,548 on vasoconstrictor responses in the hindquarters vascular bed of the cat.

The effects of SQ 29,548, a thromboxane (TX) receptor blocking agent, on vasoconstrictor responses were investigated under conditions of controlled blood flow in the hindquarters vascular bed of the cat. Intravenous injection of SQ 29,548 at a dose of 0.1 mg/kg had no significant effect on systemic arterial pressure but caused a significant reduction in hindquarters perfusion pressure.

N omega-nitro-L-arginine selectively inhibits vasodilator responses to acetylcholine and bradykinin in cats.

The effects of N omega-nitro-L-arginine (nitroarginine), an inhibitor of endothelium-dependent relaxing factor (EDRF) production, on vascular tone and responses to vasodilator and vasoconstrictor agents were investigated in the hindquarters vascular bed of the cat. Under constant flow conditions, infusion of nitroarginine into the hindquarters vascular bed caused a significant increase in systemic arterial and hindquarters perfusion pressures. During infusion of nitroarginine, hindquarters vasodilator responses to acetylcholine and bradykinin were reduced significantly whereas vasodilator responses to isoproterenol, PGE1, nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate were not altered.

Influence of SK&F 95587 and BN 50730 on bronchoconstrictor responses in the cat.

The effects of SK&F 95587 (4[2-(benzenesulfonamido)-ethyl] phenoxyacetic acid), a thromboxane (TX) receptor blocking agent, on bronchoconstrictor responses were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of the TXA2 receptor mimics, U-46619 [(15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta5Z,13E-dienoic acid] and U-44069 (9,11-dideoxy-11 alpha,9 alpha-epoxymethano PGF2 alpha), produced dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic compliance. After administration of SK&F 95587, 5 mg/kg i.

Contribution of the diethyl phosphonate group to a first approach of calcium-inhibiting activity: study of a series of various substituted 2-phenylbenzothiazoles.

Eighteen substituted 2-phenyl benzothiazoles, nine of which are new, are described. Pharmacological investigation of these Fostedil analogues did not demonstrate the same calcium inhibitory properties shown by Fostedil. The enhancement induced by the diethyl phosphonate group is confirmed.

Concentration-activity profile of the modulation of cyclooxygenase product formation by reduced glutathione in microsomal fractions from the goat lung.

Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGH2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats.

Analysis of cardiovascular and pulmonary responses to endothelin-1 and endothelin-3 in the anesthetized cat.

Cardiovascular and pulmonary responses to endothelin (ET)-1, ET-3 and neuropeptide Y (NPY) were investigated in the anesthetized cat. ET-1, 0.1 to 1 nmol/kg i.

Nisoldipine inhibits adrenergic responses in the hindquarters vascular bed of the cat.

The effects of the calcium entry blocking agent nisoldipine on adrenergic vasoconstrictor responses were investigated in the hindquarters vascular bed of the cat under conditions of controlled blood flow. Nisoldipine dilated the hindquarters vascular bed and inhibited vasoconstrictor responses to Bay K 8644, a nifedipine analog which promotes calcium entry. During infusion of nisoldipine, vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine, and tyramine were inhibited in a reversible manner.

Nisoldipine inhibits vasoconstrictor responses in the cat pulmonary vascular bed.

The influence of nisoldipine, a dihydropyridine calcium entry antagonist, on vascular resistance and vasoconstrictor responses was investigated in the feline pulmonary vascular bed under conditions of controlled blood flow. The calcium channel blocking agent caused a small reduction in lobar vascular resistance and blocked pulmonary vasoconstrictor responses to BAY K 8644, an agent which promotes calcium entry. The calcium entry blocking agent also reduced pulmonary vasoconstrictor responses to methoxamine and to BHT 933, alpha 1- and alpha 2-adrenoceptor agonists, and to U 46619, an agent which mimics the actions of thromboxane A2.