Characterization of endothelin receptors in isolated, perfused human spleen.

At present, there is no information on endothelin-1 (ET-1)-mediated vascular effects in the human spleen. The objectives of this study were to investigate the in vitro vascular responses to ET-1 using pharmacologic probes (selective ET receptor agonists/antagonists) and to characterize the ET receptor population in the human spleen. Spleens (n = 6) were removed from patients for treatment of underlying disease.

Ethanol reduces the endothelin-B receptor-mediated increase in portal inflow resistance in the isolated, perfused canine liver.

Ethanol can affect the regulation of liver hemodynamics through the release of vasoactive mediators such as nitric oxide and endothelins (ETs). The purpose of this study was to investigate the effects of ethanol on the changes in arterial and portal perfusion pressure induced by ET receptor activation. Ethanol significantly reduced portal, but not arterial perfusion pressure.

Involvement of nitric oxide in the smooth muscle tone of the isolated canine spleen and the responses to acetylcholine and substance P.

1. The canine isolated spleen was perfused at constant flow with warmed (37 degrees C) Krebs solution while the splenic arterial perfusion pressure (SAPP) and spleen weight were recorded continuously. An augmented smooth muscle tone was maintained by a continuous intra-arterial infusion of noradrenaline (0.

Characterisation of functional endothelin receptors in the canine isolated perfused spleen.

The endothelin receptor subtypes involved in the vasoconstriction, capsular smooth muscle contraction, prostaglandin E2 and prostacyclin release induced by endothelin-1 have been investigated in the canine isolated perfused spleen using both the endothelin ETA receptor antagonist FR 139317 and the endothelin ETB receptor agonist IRL 1620. THe isolated canine spleen was perfused with warmed (37 degrees C) and oxygenated (95% O2/5% CO2) Krebs solution at constant flow with continuous recording of splenic arterial perfusion pressure and spleen weight. Samples of splenic venous effluent were collected to determine the amounts of prostaglandin E2 and prostacyclin, measured by radioimmunoassay.

Role of endothelin ETA and ETB receptors in the arterial vasculature of the isolated canine liver.

The vascular effects of endothelin-1 (ET-1; ETA/ETB agonist), sarafotoxin 6b (S6b; ETA agonist), and IRL 1620 (ETB agonist) were investigated in the isolated canine liver arterial circuit before and after infusions of indomethacin (cyclo-oxygenase inhibitor) and N omega L-nitro arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor). Norepinephrine (NE) was used as vasconstrictor control agent. The portal vein, hepatic artery, and vena cava were cannulated in vitro and the liver was perfused via the hepatic artery and portal vein with oxygenated (95%) O2/5% CO2) Krebs solution at 37 degrees C.

The effects and molar potency of iloprost, U46619 and sodium nitroprusside on capsular and vascular smooth muscle of the isolated perfused canine spleen.

The isolated canine spleen was perfused at constant flow with continuous recording of splenic arterial perfusion pressure (SAPP) and spleen weight. Intra-arterial injections of the thromboxane A2 (TXA2) mimetic U46619 caused dose-related increases in splenic arterial perfusion pressure (SAPP) of short duration (ED50 0.31 nmol).

Modulation by endogenous prostanoids of the vasoconstrictor activity of endothelin-1 in the canine isolated, perfused spleen.

1. Endothelin-1 (ET-1, 0.4-200 pmol) was injected into the arterial circuit of the isolated perfused spleen of the dog in which splenic arterial perfusion pressure and spleen weight were recorded continuously.

The actions of two sensory neuropeptides, substance P and calcitonin gene-related peptide, on the canine hepatic arterial and portal vascular beds.

1. The two peptides, calcitonin gene-related peptide (CGRP) and substance P (SP) were administered individually as bolus injections into the separately perfused hepatic arterial and portal vascular beds of the anaesthetized dog to assess their actions and relative molar potencies at these sites. 2.

The actions of endothelins-1 and -3 on the vascular and capsular smooth muscle of the isolated blood perfused spleen of the dog.

1. Endothelin-1 (ET-1), endothelin-3 (ET-3) and noradrenaline (NA) were administered as intra-arterial bolus injections into the isolated, blood-perfused spleen of the dog to assess agonist properties and relative molar potencies on the vascular and capsular smooth muscle. 2.

The actions of human atrial natriuretic factor on hepatic arterial and portal vascular beds of the anaesthetized dog.

1. The vascular actions of atrial natriuretic factor (ANF) have been assessed with other vasoactive agents on the hepatic arterial and portal vascular beds of the anaesthetized dog. 2.

The relaxant properties of human calcitonin gene-related peptide on vascular and extravascular capsular) smooth muscle of the isolated blood-perfused spleen of the anaesthetized dog.

1. The 37 amino acid human calcitonin gene-related peptide (CGRP), was injected intra-arterially into the isolated, blood perfused spleen of the dog. 2.

Endothelin-1 causes vasoconstriction and vasodilation in the blood perfused liver of the dog.

Endothelin-1 (ET-1; 1 pmol-1 nmol) was injected intra-arterially into the canine hepatic artery perfused, in situ, with arterial blood. The characteristic arterial vascular response to ET-1 was biphasic consisting of an initial increase in flow (vasodilatation) of short duration followed by a prolonged reduction in flow (vasoconstriction). The hepatic portal circuit was perfused at a constant flow with blood derived from the mesenteric circuit.

A comparison of the differential effects of vasoactive intestinal peptide and peptide histidine isoleucine on the vascular and capsular smooth muscle of the dog spleen.

1. The actions of the two peptides, vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) have been compared to that of isoprenaline on the smooth muscle systems of the isolated blood-perfused dog spleen. 2.

The actions of neuropeptide Y and peptide YY on the hepatic arterial and portal vascular beds of the anaesthetized dog.

1. The vascular actions of the two peptides, neuropeptide Y (NPY) and peptide YY (PYY) were compared with the transmitter noradrenaline (NA) on the arterial and portal vascular beds of the in situ liver of the anaesthetized dog. 2.

The actions of the peptides, neuropeptide Y and peptide YY, on the vascular and capsular smooth muscle of the isolated, blood-perfused spleen of the dog.

The two peptides, neuropeptide Y (NPY) and peptide YY (PYY) were compared for potency on the vascular and extravascular smooth muscle of the isolated, blood-perfused spleen of the dog. The only vascular response to both NPY and PYY was vasoconstriction; the maximum effect was to arrest splenic arterial blood flow completely. On a molar basis both NPY and PYY were significantly more potent (P less than 0.

Erythrocyte uptake by the dog's spleen during splenic venous pressure elevation.

The spleens of chloralose-urethane anaesthetized dogs were isolated, placed in a plethysmograph and perfused at constant arterial pressure from a cannulated femoral artery. Splenic venous pressure (PV) was elevated by between 2.5 and 20 cm H2O: it caused pressure-dependent increases in spleen volume of up to 98 +/- 12 ml/100 g spleen weight.

The effects of intraportal infusions of glucagon on the hepatic arterial and portal venous vascular beds of the dog: inhibition of hepatic arterial vasoconstrictor reponses to noradrenaline.

The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. Glucagon was infused into the hepatic portal vein (1--10 microgram/min); it caused increases in hepatic portal vascular resistance and tended to reduce the hepatic arterial vascular resistance. Extrahepatic effects of intraportal infusions of glucagon included increases in superior mesenteric blood flow and heart rate and falls in systemic arterial pressure.

Responses of the simultaneously-perfused hepatic arterial and portal venous vascular beds of the dog to histamine and 5-hydroxytryptamine.

1 The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. 2 Histamine and 5-hydroxytryptamine (5-HT) were injected intra-arterially and intraportally in graded, increasing doses. 3 Intra-arterial histamine evoked decreases in hepatic arterial vascular resistance (HAVR) and increases in hepatic portal vascular resistance (HPVR).