OBJECTIVETo identify and elucidate the vasorelaxant activity of homoisoflavonoids, the main chemical components from Lignum Sappan (the stems of Caesalpinia sappan), in isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 micromol x L(-1)) and KCl (60 mmol x L(-1)).

METHODThe tension of rat thoracic aorta rings was used to evaluated the vasorelaxant activities of four homoisoflavonoids, brazlin (1), (E)-3-(3,4-dihydroxybenzylidene)-7-hydroxychroman-4-one (2), sappanone B (3), 3-deoxysappanone B (4).

RESULTCumulative addition of homoisoflavonoids (2, 3 and 4) (50-1000 micromol x L(-1)) exhibited an acute relaxation either in endothelium-intact or endothelium-denuded rings in a concentration-dependent manner. However, this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of endothelial nitric oxide synthase (eNOS) inhibitor, N(W)-nitro-L-arginine methyl ester (L-NNA, 100 micromol x L(-1)), and a soluble guanylate cylcase (sGC) inhibitor, methylene blue (MB, 10 micromol x L(-1)) when addition of variation homoisoflavonoids brazlin (1) (50-1000 micromol x L(-1)).

CONCLUSIONThese results indicate that normo-homoisoflavonoids (2, 3 and 4) from Caesalpinia sappan mediates endothelium-independent vasodilator action in rat thoracic aortic rings, while the variation homoisoflavonoids brazlin elicits endothelium-dependent relaxation might via nitric oxide (NO)-cGMP pathway. This research could explain the pharmacological activities of homoisoflavonoids to a certain degree.

Animals ; Aorta, Thoracic ; drug effects ; physiology ; Caesalpinia ; chemistry ; Endothelium ; metabolism ; Enzyme Inhibitors ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Guanylate Cyclase ; antagonists & inhibitors ; Male ; Muscle Contraction ; drug effects ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase Type III ; antagonists & inhibitors ; Phenylephrine ; pharmacology ; Potassium Chloride ; pharmacology ; Rats ; Receptors, Cytoplasmic and Nuclear ; antagonists & inhibitors ; Soluble Guanylyl Cyclase ; Vasodilation ; drug effects ; Vasodilator Agents ; chemistry ; pharmacology

OBJECTIVETo investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

METHODSThe ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

RESULTSPreconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

CONCLUSIONBAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.

Animals ; Area Under Curve ; Berberis ; chemistry ; Blood Pressure ; drug effects ; Cyclic GMP ; metabolism ; Epoprostenol ; pharmacology ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Models, Biological ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Penile Erection ; drug effects ; Phenylephrine ; pharmacology ; Plant Extracts ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Pressure ; Rabbits

The purpose of this study was to determine if mild hypoxia alters the responsiveness to vasoactive agents in the renal and the femoral arteries in the fetal sheep. Ten pregnant sheep were operated under halothane anesthesia at 116 to 124 days' gestation. A maternal tracheal catheter was placed for infusing compressed air (control group, n=5) or nitrogen (hypoxia group, n=5) starting on post operative day 6 and maintained for 5 days. Femoral and renal arteries were harvested from the fetus to study the constriction response to phenylephrine (PE 10(-9) to 10(-5) mol/L). To determine the involvement of nitric oxide as a modulator of vessel constriction, N-nitro-Larginine methyl ester (L-NAME) was used at a concentration of 10(-4) mol/L in parallel chambers. In the hypoxia group, maternal Pao2 significantly decreased from a base-line of 110.4 +/-1.4 to 80.5 +/-1.6 (mmHg, p <0.01), fetal Pao2 significantly decreased from a baseline of 20.9 +/-0.3 to 15.5 +/-0.1 (mmHg, p <0.01). Hypoxia was associated with a significant increase in PE maximal response in the absence (184.5 +/-6.6 vs. 146.2 +/-4.3) and presence (166.9 +/-6.3 vs. 145.0 +/-4.5) of L-NAME, and a decrease in EC50 in the absence (6.0 +/-1.1 vs. 27.0 +/-4.1) of L-NAME of femoral arteries. However, there were no significant differences in PE maximal response and EC50 in the absence and presence of L-NAME of renal arteries. We concluded that mild chronic hypoxia seems to increase the fetal femoral artery response to PE, but not in the fetal renal artery. This observation is consistent with a redistribution of cardiac output away from the carcass.
Animals ; *Anoxia ; Blood Glucose/metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Femoral Artery/*embryology/*pathology ; Hematocrit ; Hydrogen-Ion Concentration ; Kidney/blood supply ; Lactates/blood/metabolism ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/metabolism ; Nitric-Oxide Synthase/antagonists & inhibitors ; Phenylephrine/chemistry/metabolism/pharmacology ; Renal Artery/pathology ; Sheep/*embryology ; Time Factors ; Vasoconstrictor Agents/*pharmacology

AIMTo investigate the inhibitory effects and mechanism of action of isoliensinine (IL) on the proliferation of porcine coronary arterial smooth muscle cells (CASMCs) induced by phenylephrine (Phen) and its mechanisms of action.

METHODSMTT assay, immunohistochemical method and Western blotting were adopted.

RESULTSIL (0.03 - 3 micromol x L(-1)) could inhibit the CASMCs proliferation induced by Phen (0.1 micromol x L(-1)) in a concentration-dependent manner. IL (0.1 micromol x L(-1)) antagonized Phen-induced overexpression of PDGF-beta and bFGF from 0.545 +/- 0.026 and 0.47 +/- 0.03 to 0.458 +/- 0.019 and 0.376 +/- 0.017 (P < 0.01 , P < 0.01). IL (0.1 micromol x L(-1)) also decreased c-fos, c-myc and hsp70 overexpression induced by Phen from 0.57 +/- 0.04, 0.44 +/- 0.04 and (173 +/- 36)% to 0.46 +/- 0.05, 0.372 +/- 0.021 and (115 +/- 35)% respectively (P < 0.01, P < 0.01, P < 0.01).

CONCLUSIONIL exerted antiproliferative effect on CASMCs induced by phenylephrine, and its mechanisms were related to decrease the overexpression of growth factors (PDGF-beta, bFGF), protooncogene (c-fos, c-myc) and hsp70.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Coronary Vessels ; cytology ; Dose-Response Relationship, Drug ; Fibroblast Growth Factor 2 ; metabolism ; HSP70 Heat-Shock Proteins ; metabolism ; Isoquinolines ; administration & dosage ; isolation & purification ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Nelumbo ; chemistry ; Phenylephrine ; antagonists & inhibitors ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; Proto-Oncogene Proteins c-sis ; metabolism ; Swine