Animals ; Aorta, Thoracic ; physiology ; Dopamine ; pharmacology ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Rats ; Vasoconstriction ; drug effects

Animals ; Aorta ; drug effects ; physiology ; Blood Pressure ; drug effects ; Cadmium ; toxicity ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Rabbits ; Vasoconstriction ; 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

AIMTo examine the effect of HO-1 inducer hemin on hydrogen peroxide (H2O2) caused decrease in contraction of isolated rat aortic rings, and to elucidate the underlying mechanism.

METHODSThe thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured.

RESULTS(1) After intraperitoneal injection of HO-1 inducer hemin, HO-1 activity of thoracic aorta and COHb concentration in rat blood enhanced. And it also prevented the decrease in contraction responses to PE which pretreatment of arteries with 300 micromol/L H2O2. (2) Pretreatment of ATP-sensitive potassium channel inhibitor glibenclamide, but not GC inhibitor methylene blue, could partly abolish the protection of hemin in arteries with H2O2 exposure. (3) Hemin could not influence the shift of concentration-response curve to [Ca2+]o in arteries with H2O2 exposure. (4) In Ca(2+) -free K-H solution, exposure of H2O2 reduced caffeine and PE-induced constriction in the rat aortic rings. After pretreatment of hemin, could prevent the decrease in contraction responses to caffeine and PE.

CONCLUSIONIncrease in HO-1 activity could prevent the H2O2 induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be involved in activation of ATP-sensitive potassium channel and mobilization of intracellular calcium stores, but had no relationship with the GC pathway.

Animals ; Aorta, Thoracic ; drug effects ; physiology ; Endothelium, Vascular ; Heme Oxygenase-1 ; pharmacology ; Hydrogen Peroxide ; adverse effects ; KATP Channels ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects

The aim of the present study was to investigate whether protein kinase C (PKC) was involved in the effect of mesenteric lymph duct ligation or mesenteric lymph drainage on vascular calcium sensitivity in hemorrhagic shock rats. Male Wistar rats were randomly divided into Sham, Shock (hemorrhagic shock), Shock+Ligation (mesenteric lymph duct ligation plus shock) and Shock+Drainage (mesenteric lymph drainage plus shock) groups. After being in shock (hypotension 40 mmHg) for 3 h, the tissue of superior mesenteric artery (SMA) was taken out for detecting the PKC expression and phospho-PKC (p-PKC) activity, and the vascular rings of SMA were prepared and used to measure the response to gradient calcium concentration for assaying the calcium sensitivity, the parameters of which including tension, maximum tension (E(max)) and negative logarithm of EC(50), called the pD(2). Other vascular rings from Shock+Ligation and Shock+Drainage groups were incubated with PKC regulator PMA or Staurosporine before the measurement of calcium sensitivity. The results showed that, PKC expression, p-PKC activity and calcium sensitivity of SMA in Shock group was significantly lower than that of Sham group, whereas the above-mentioned indexes were significantly elevated in Shock+Ligation and Shock+Drainage groups compared with those in Shock group. PKC agonist PMA enhanced the contractile activity of vascular rings to gradient calcium ions, and increased E(max) of SMA in Shock+Ligation and Shock+Drainage groups. On the contrary, PKC inhibitor Staurosporine significantly decreased the response to gradient calcium ions and E(max) of SMA in Shock+Ligation and Shock+Drainage groups. These results suggest that PKC plays a role in the improvement of vascular calcium sensitivity by blockade of mesenteric lymph return in hemorrhagic shock rats.
Animals ; Calcium ; pharmacology ; Drainage ; Ligation ; Lymph ; physiology ; Lymphatic Vessels ; physiology ; Male ; Mesenteric Artery, Superior ; drug effects ; physiology ; Mesentery ; Muscle, Smooth, Vascular ; drug effects ; metabolism ; Protein Kinase C ; metabolism ; physiology ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; physiopathology ; Vasoconstriction ; drug effects ; physiology

Although hypoxic pulmonary vasoconstriction (HPV) has been recognized by many researchers, the precise mechanism remains unknown. As isolated pulmonary arteries will constrict in vitro in the response to hypoxia, the oxygen sensor/transduction mechanism must reside in the pulmonary arterial smooth muscle or in the endothelium, or in both. Unfortunately, much of the current evidence is conflicting, especially as to the dependency of HPV on the endothelium and the role of a K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPV on the endothelium and the role of a K+ channel on HPV in rat pulmonary artery. The effects of hypoxia were investigated in isolated main pulmonary arteries precontracted with norepinephrine. Vascular rings were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and this was maintained for 20 min. Hypoxia elicited a vasoconstriction in arteries with endothelium. Mechanical disruption of the endothelium abolished HPV. There was no difference between the amplitude of the HPV induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on a subsequent response to hypoxia. Inhibition of NO synthesis by treatment with N(omega)-nitro-L-arginine reduced HPV, but inhibition of a cyclooxygenase pathway by treatment with indomethacin had no effect on HPV. Blockades of a tetraetylammonium chloride-sensitive K+ channel abolished HPV. Verapamil, a Ca2+ entry blocker reduced HPV. In conclusion, these results suggest that HPV was dependent on the endothelium and that HPV can be considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation such as the opening of a K+ channels.
Animal ; Anoxia/physiopathology* ; Blood Vessels/physiopathology ; Calcium Channel Blockers/pharmacology ; Cyclooxygenase Inhibitors/pharmacology ; Enzyme Inhibitors/pharmacology ; Indomethacin/pharmacology ; Nitroarginine/pharmacology ; Pulmonary Circulation/physiology* ; Pulmonary Circulation/drug effects ; Rats ; Tetraethylammonium/pharmacology ; Vasoconstriction/physiology* ; Vasoconstriction/drug effects ; Verapamil/pharmacology

OBJECTIVETo investigate the role of voltage-gated potassium channels in the acute hypoxic pulmonary vasoconstriction.

METHODSThirty Wistar rats were divided into two groups, namely the normoxic group and hypoxic group. The single smooth muscle cell was obtained from the pulmonary artery of Wistar rats with acute enzymatic digestion method. The conventional whole-cell patch clamp technique was used to record the resting membrane potential(Em) and the potassium currents of voltage-gated potassium channel (IKv) in rat pulmonary arterial smooth muscle cells(PASMC). Intracellular application of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 antibodiesè1:125éwas conducted through the whole-cell patch clamp system.

RESULTSEm of PASMC was depolarized in hypoxia compared with that of control cells. The mixture of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 antibodiesè1:125é depolarized Em and inhibited Ikv in PASMC from normoxic rat,whereas the mixture of Kv1.2, Kv1.3, Kv1.5, Kv2.1 antibodiesè1:125éhad no effects on Ikv and Em in hypoxic rats.

CONCLUSIONKv1.2, Kv1.3, Kv1.5, Kv2.1 might be oxygen sensitive potassium channels which mediated acute hypoxic pulmonary vasoconstriction.

Animals ; Hypoxia ; physiopathology ; Membrane Potentials ; drug effects ; Muscle, Smooth, Vascular ; physiopathology ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; physiology ; Pulmonary Artery ; pathology ; physiology ; Rats ; Rats, Wistar ; Vasoconstriction ; physiology

AIMTo investigate the effects of atrial natriuretic peptide(ANP) on constriction and relaxation of pulmonary artery and aorta in endotoxemia rat in vitro.

METHODS24 male SD rats were randomly divided into 3 groups, control group, LPS group, ANP therapy group. These groups were injected physiologic salt water, lipopolysaccharide (LPS 2 mg/kg) and LPS + ANP(LPS 2 mg/kg, ANP 2 microg/kg) into vein respectively. After 4 hours, rats were exsanguinated to kill and aorta and pulmonary artery were separated from heart-lung for experiment of blood vessel rings. Constriction effects of aorta and pulmonary artery by norepinephrine (NE), relaxation of aorta and pulmonary artery by acetylcholine (ACh) and sodium nitroprusside SNP) observed by perfusion system in vitro.

RESULTSSensitiveness of NE-induced (10(-9)-10(-7) mol/L) constriction of aorta in LPS group was attenuated and EC50 was increased, but its strength (3 x 10(-7)-10(-6) mol/L) was greater comparing with control group (P < 0.01). In ANP group, the NE-induced contractility of aorta was similar to LPS group (P > 0.05). Comparing with control group, NE-induced constriction of pulmonary artery exposure to LPS was reinforced especially in 3 x 10(-7)-10(-6) mol/L of NE (P < 0.01), but its EC50 was obviously higher (P <0.05). There was no significant difference between ANP group and control group in constriction of pulmonary artery (P > 0.05). Relaxation and sensitiveness of aorta and pulmonary artery exposure to LPS were evidently improved in ANP therapy group induced by ACh and SNP respectively (P < 0.01, P < 0.05) and their EC50 markedly decreased comparing with LPS group (P < 0.01, P < 0.05) respectively.

CONCLUSIONANP can suppress the reinforcing of NE-induced constriction of pulmonary artery exposure to LPS and partly or entirely reverse the attenuated relaxation of pulmonary artery and aorta induced by ACh and SNP in endotoxemia rats.

Acetylcholine ; pharmacology ; Animals ; Aorta ; drug effects ; physiology ; Atrial Natriuretic Factor ; pharmacology ; Endotoxemia ; physiopathology ; Male ; Nitroprusside ; pharmacology ; Norepinephrine ; pharmacology ; Pulmonary Artery ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

OBJECTIVECrassostrea gigas oyster extract has been reported to have antioxidant, antihypertensive and lipid-lowering properties that may be useful for treating cardiovascular diseases. This study aimed to evaluate the effect of C. gigas oyster extract on cardiovascular function in tissues from healthy rats.

METHODSSingle-cell microelectrode and isolated thoracic aortic organ bath studies were performed on tissues from 8-week-old healthy Wistar rats, using varying concentrations of C. gigas oyster extract. To elucidate a mechanism of action for the oyster's vasoactive properties, concentration response curves were carried out in the presence of a calcium channel inhibitior (verapamil), a nitric oxide synthase inhibitor (N(G)-nitro-L-arginine methyl ester), a potassium channel inhibitor (4-aminopyridine), in addition to the α-adrenoceptor inhibitor prazosin.

RESULTSOyster solution at 7 500 mg/mL inhibited noradrenaline-induced contraction in isolated aortic rings. Cardiac electrophysiology results showed that neither concentration of oyster solution was able to significantly reduce action potential duration at all phases of repolarisation in left ventricular papillary muscles from healthy animals.

CONCLUSIONWhen administered to healthy vascular tissue, C. gigas oyster extract inhibits contraction induced by noradrenaline. This effect is likely to be mediated through α-adrenoceptor inhibition, and to a lesser extent, calcium modulating activity.

Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Calcium ; metabolism ; Crassostrea ; Heart ; drug effects ; physiology ; Male ; Norepinephrine ; antagonists & inhibitors ; pharmacology ; Rats ; Rats, Wistar ; Vasoconstriction ; drug effects

OBJECTIVETo investigate the acute effects of aldosterone (ALD) on mesenteric resistance vessels in normal or heart failure (HF) rats and its mechanism.

METHODSHF model was adopted by in vivo ligation of left anterior descending coronary artery in SD rats; segments of third-order branches of mesenteric artery were isolated and dissected into about 2 mm rings for isometric force recording.

RESULTSPretreated with ALD for 10 min,phenylephrine (PE)-induced contraction of normal mesenteric artery decreased first and then increased compared to control group along with the increase of the concentration of PE while decreased in HF rats. This effect was attenuated by ALD receptor-special antagonist eplerenone partially. ALD increased Ach-induced endothelial-dependent vascular relaxation significantly compared to control group both in normal and HF rats. Pretreated with ALD and dexamethasone (DEX) for 10 min, the effects of ALD on PE-induced contraction were weakened in mesenteric artery both of normal and HF rats. And this reaction of DEX to ALD-treated mesenteric in normal rats was attenuated by RU486 partially.

CONCLUSIONALD has biphasic effect in PE-induced response on mesenteric artery of normal rats, while reduces the sensitivity of mesenteric artery to PE in HF rats. DEX attenuates the biphasic effect of ALD on artery of normal rat partially but has no significant effect on that of HF rats.

Aldosterone ; pharmacology ; Animals ; Heart Failure ; physiopathology ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Phenylephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects