The purpose of this study was to investigate the vasorelaxing effect and mechanism of idoxifene (a new estrogen receptor modulator) on human internal mammary artery (HIMA). HIMA segments were harvested from men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, or smoking habit were excluded. The vasorelaxing effect of idoxifene on artery rings from HIMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to idoxifene in the range of 0.01-10 micromol/L was observed in the presence and absence of NO synthase inhibitor L-NAME. It was also studied whether the vasodilation effect of idoxifene on HIMA was blocked by methylene blue (MB), an inhibitor of guanylate cyclase (GC). The results obtained from idoxifene were compared with those from 17beta-estradiol (E(2)). It was found that idoxifene caused a concentration-dependent relaxation on HIMA. The dose range was from 0.03 micromol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E(2) (0.1-100 micromol/L) also resulted in an endothelium-dependent vasorelaxation, but the vessels were 15-fold less sensitive to E(2) than to idoxifene in their vasorelaxation responses. The EC(50) for E(2) was 4.65+/-0.34 micromol/L, compared with 0.32+/-0.02 micromol/L for idoxifene. The mean maximal vasodilatory value of E(2) was 88.3+/-5.7%, compared with 88.6+/-7.2% for idoxifene. Pretreatment with L-NAME (100micromol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presence of MB (10 micromol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.
Estrogen Antagonists ; pharmacology ; Humans ; Mammary Arteries ; drug effects ; physiology ; Tamoxifen ; analogs & derivatives ; pharmacology ; Vasodilation ; drug effects

AIMTo compare the differences of pharmacological characteristics of the endothelial target for acetylcholine (ETA) between rat aorta and tail artery.

METHODSDifferences in the endothelium-dependent relaxation induced by acetylcholine (ACh: 10(-8) - 10(-4) mol/L) were studied using isolated rat tail artery helical strips and aortic rings, so that the pharmacological characteristics of ETA in small artery can be observed.

RESULTSACh-induced endothelium-dependent relaxation was observed both in rat tail artery strips and in aortic rings precontracted with potassium chloride (60 mmol/L) in a concentration-dependent manner. In tail artery this effect was partially blocked by L-N(omega)-Nitro-arginine methyl ester (L-NAME: 10(-4) mol/L) or methylene blue (MB: 10(-5) mol/L), together with indomethacin (Indo: 10(-4) mol/L), but in aorta it was completely blocked by L-NAME or MB.

CONCLUSIONIt is different of the pharmacological characteristics of ETA between big artery and small artery. A non-NO and non-PGI2 relaxing factor, together with nitric oxide (NO) and prostacyclin (PGI2), mediates endothelium-dependent vasorelaxation induced by ACh in small artery, but NO may be the principal endothelial vasodilator substance in big artery.

Acetylcholine ; pharmacology ; Animals ; Aorta ; drug effects ; Arteries ; drug effects ; Endothelium, Vascular ; drug effects ; physiology ; In Vitro Techniques ; Male ; Rats ; Rats, Wistar ; Vasodilation ; drug effects

Rhizoma Polygoni Cuspidati, a Chinese herbal drug, has actions of dispelling dampness, alleviating jaundice, clearing heat, subsiding toxin, activating blood, and removing stasis. Polydatin (PD), one of its chief active ingredients, has been proved by modern pharmacological studies to possess extensive cardiovascular pharmacological activity, showing marked effects on protecting cardio-myocyte, dilating blood vessel, antagonizing platelet aggregation, thrombosis, and atherosclerosis. The progress of the research on cardiovascular pharmacological actions and the acting mechanism of PD was reviewed in this paper.
Biomedical Research ; trends ; Cardiovascular System ; drug effects ; Glucosides ; pharmacology ; Humans ; Lipid Peroxidation ; drug effects ; Myocytes, Cardiac ; drug effects ; Stilbenes ; pharmacology ; Vasodilation ; drug effects

People complain about nasal stuffiness after SO2 exposure. This study was to investigate the acute effects of SO2 on nasal vascular and airway resistances in anaesthetized pigs for elucidating the underlying vascular and control mechanisms. Controlled ventilation was passed to the lungs or retrogradely through each nasal cavity. Nasal airway and lower airway pressures were measured to reflect airflow resistance changes. Systemic arterial pressure and nasal arterial flow were measured to calculate nasal vascular resistance. Nasal and pulmonary SO2 challenges were given. At 2 ppm, SO2 decreased systemic blood pressure and nasal vascular resistance but increased nasal airway and lower airway resistances. With increasing level to 8 ppm, SO2 increased systemic arterial pressure, nasal vascular and lower airway resistances but decreased nasal airway resistance. Nasal and pulmonary challenges induced similar responses. Ipsilateral nasal challenge elicited bilateral responses. Ruthenium red abolished the responses to nasal challenges. Bilateral vagosympathectomy eliminated the responses to lung challenges. Hence, SO2 at 2 ppm causes nasal congestion through sensory reflex vasodilatation but at higher levels nasal decongestion through sensory reflex vasoconstriction. Nasal congestion coupled with bronchoconstriction at levels of SO2 below short-term exposure limit (STEL) (≤ 2 ppm) would limit SO2 entering the lungs. Nasal decongestion at levels of SO2 beyond STEL (> 2 ppm) can effectively decrease total airway resistance as concurrent strong bronchoconstriction may impair ventilation.
Administration, Inhalation ; Airway Resistance ; drug effects ; Animals ; Lung ; drug effects ; Nasal Cavity ; drug effects ; Respiration ; Sulfur Dioxide ; pharmacology ; Swine ; Vascular Resistance ; drug effects ; Vasodilation

OBJECTIVETo investigate the vasorelaxant effect of taurine (Tau) in rat aortic rings and the mechanism.

METHODThe isolated thoracic aortic rings of male Wistar rats were mounted on the organ bath. The effect of Tau 10, 20, 40, 80 mmol x L(-1) on the rings with endothelium intact or endothelium denuded precontracted by the phenylephrine (1 micromol x L(-1)) or KCl (60 mmol x L(-1)), and the effect of Tau on the vessel reaction induced by various drugs were recorded with biological signal analytical system.

RESULTTaurine completely relaxed the contractions induced by KCl and phenylephrine in a concentration-dependent manner in endothelium-intact and endothelium-denuded rat aorta. Taurine attenuated the contraction to PE both in the absence and presence of calcium, but had no significant effect on the contraction induced by caffeine. The relaxant effect of taurine was significantly inhibited by pretreatment of endothelium-denuded aorta with potassium channel antagonists glibenclamide and tetraethylamine but not by BaCl2 or 4-aminopyridine.

CONCLUSIONTaurine induces an endothelium-independent relaxation in rat aortic rings. The mechanisms may involve the reduction in Ca2+-influx and Ca2+-release and the participation of the potassium channels (KATP and KCa, but not Kir or KV).

Animals ; Aorta ; drug effects ; physiology ; Endothelium, Vascular ; drug effects ; physiology ; Male ; Models, Animal ; Muscle Relaxation ; drug effects ; Rats ; Rats, Wistar ; Taurine ; pharmacology ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

OBJECTIVETo observe the effect of the main constituents and its combination from Chuanxiong Fangfeng Baizhi prescription on isolated rabbit basilar artery.

METHODThe isolated rabbit basilar artery rings were treated with 5 mmol x L(-1) KCl and 5-HT 2.4 x 10(-8) mol x L(-1), and by measuring the tension of basilar artery rings, the effect of the main constituents and its combination from Chunxiong Fangfeng Baizhi Prescription on vascular activity was observed.

RESULTUnder pre-contractions of KCl 45 mmol x L(-1), ligustilide, ferulic acid, imperatorin and two constituent's combination have the vasodilatation effect on rabbit basilar artery rings white prim-o-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-o-methylvisamminol have no same action. The EC50 sequence is P2 < imperatorin < ligustilide < P1 (P < 0.05). And the same vasodilatation effect on rabbit isolated basilar artery rings evoked by 5-HT 2.4 x 10(-8) mol x L(-1) was found for two constituents' combination.

CONCLUSIONExcept prim-o-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-o-methylvisamminol, all samples have the vasodilatation effect on rabbit isolated basilar artery rings evoked by KCl and 5-HT, the vasodilatation effect of constituent's combination were better than any single constituent.

Animals ; Apiaceae ; chemistry ; Basilar Artery ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; In Vitro Techniques ; Male ; Prescriptions ; Rabbits ; Vasodilation ; drug effects

Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium-Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF.
Animal ; Aorta/drug effects/physiology ; In Vitro ; Membrane Potentials/drug effects ; Potassium/pharmacology ; Potassium Channels/physiology ; Rabbits ; Support, Non-U.S. Gov't ; Tetraethylammonium Compounds/pharmacology ; Vanadates/*pharmacology ; Vasodilation/*drug effects

AIMTo investigate the mechanisms of vasodilatation of plant-derived estrogen biochanin A.

METHODSIsolated aortic ring preparations from Sprague-Dawley rats were suspended in individual organ baths. The tension was measured isometrically.

RESULTSBiochanin A at the range of 10(-9)-10(-4) mol/L provoked concentration-dependent and endothelium-independent relaxation of the rings constricted by phenylephrine (10(-5) mol/L). Biochanin A caused concentration-dependent relaxation of denuded rings precontracted with KCl (6 x 10(-2) mol/L). Glibenclamide (3 x 10(-6) mol/L), a selective inhibitor of ATP-sensitive potassium channels, and tetraethylammonium (5 x 10(-3) mol/L), a Ca2+ -activated K+ channel inhibitor, significantly attenuated the relaxation induced by biochanin A. The vasoconstriction induced by phenylephrine was decreased by biochanin A in Ca2+ -free medium.

CONCLUSIONThe endothelium-independent relaxation of thoracic aorta induced by biochanin A might be mediated by ATP-sensitive K+ channels, Ca2+ -activated K+ channels and intracellular Ca2+ release from sarcoplasmic reticulum.

Animals ; Aorta, Thoracic ; drug effects ; physiology ; Genistein ; pharmacology ; In Vitro Techniques ; KATP Channels ; metabolism ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects

The purpose of the present study was to investigate the effect of 17beta-estradiol (17beta-E(2)) on the structure and relaxation and contraction activity of thoracic aortas in ovariectomized rats with insulin resistance induced by fructose. Ovariectomized mature female Sprague-Dawley rats were fed with high fructose diet for 8 weeks to induce insulin resistance. Physiological dose of 17beta-E(2) (30 mug/kg) was injected subcutaneously every day for 8 weeks. Systolic blood pressure (SBP) was measured by use of tail-cuff. Serum nitric oxide (NO), estradiol (E(2)), fasting blood sugar (FBS) and fasting serum insulin (FSI) were measured respectively in each group. The insulin sensitive index (ISI) was calculated. The thoracic aortas were fixed in formalin, sliced and HE dyed. The structure of thoracic aortas, lumen breadth, media thickness, media thickness/lumen breadth ratio and media cross-section area were measured. The contraction response of thoracic aorta rings induced by L-phenylephrine (PE) and the relaxation response of thoracic aorta rings induced by ACh and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) was used. The results obtained are as follows: (1) 17beta-E(2) protected against the effect of high fructose diet, which caused an increase in SBP, hyperinsulinemia and a decrease in ISI in ovariectomized rats. (2) The structure of thoracic aortas had no significant difference among the groups. (3) Compared with the ovariectomized group (OVX) or fructose fed group (F), serum nitric oxide was significantly reduced, the contraction response of thoracic aorta rings to PE was enhanced and the relaxation response to ACh was depressed significantly in ovariectomized+fructose fed group (OVX+F). The effect of high fructose was reversed by 17beta-E(2). After pretreatment with L-NAME, the effect of 17beta-E(2), which enhanced the relaxation response of thoracic aorta rings to ACh in ovariectomized+fructose+17beta-E(2) group (OVX+F+E(2)), was partly blocked. (4) The relaxation response of thoracic aorta rings to SNP had no significant difference among the groups. (5) The contraction response of thoracic aorta rings without endothelium to PE had no significant difference among the groups. These findings suggest that 17beta-E(2) may provide protection against the effect of high fructose diet, which causes hypertension, dysfunction of endothelial cells and insulin resistance. The mechanism of this effect of 17beta-E(2) could be partly associated with the increase of NO by NOS pathway, or associated with the decrease in the level of systolic blood pressure and serum insulin, and the improvement of insulin resistance.
Animals ; Aorta ; physiology ; Estradiol ; pharmacology ; Female ; Fructose ; Insulin Resistance ; physiology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects ; Vasomotor System ; drug effects

To investigate the effect of peroxynitrite (ONOO(-)) on the reactivity of rabbit pulmonary artery, the responses of rabbit pulmonary artery rings (PARs) pre-incubated with ONOO(-) to endothelium-dependent and receptor-dependent relaxants ACh and ADP, endothelium-dependent and receptor-independent relaxant calcium ionophore A23187, endothelium-independent relaxant sodium nitroprusside (SNP) and alpha(1)-adrenoceptor agonist phenylephrine (PE) were observed in vitro in an accumulative manner. (1) Relaxations of PARs to ACh, calcium ionophore A23187 and ADP were markedly impaired with shift of accumulative dose-response curve of each agonist to the right. Inhibition of endothelium-dependent and receptor-dependent or independent relaxation by ONOO(-) was dose-dependent. (2) ONOO(-) incubation inhibited SNP-induced relaxation in a dose-dependent manner. (3) Contractile response of PARs to PE varied with the different doses of ONOO(-). In PARs pre-incubated with 0.5 mmol/L ONOO(-), contractile response was significantly enhanced with shift of PE accumulative dose-response curve to the left, whereas in PARs pre-incubated with 1.0 mmol/L or 2.0 mmol/L ONOO(-), it was markedly reduced with right shift of PE accumulative dose-response curve. (4) Vehicle of ONOO(-) had no effect on responses to each agonist.Decomposed ONOO(-) had minimal effect on the response to PE and ADP, in contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results indicate that ONOO(-) may contribute to regulatory disorder of pulmonary artery reactivity.
Animals ; Dose-Response Relationship, Drug ; In Vitro Techniques ; Peroxynitrous Acid ; physiology ; Pulmonary Artery ; physiology ; Rabbits ; Vasodilation ; drug effects