This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of rabbits and mean arterial blood pressure (MAP) and renal nerve discharges (FRND) were synchronously recorded. The results indicated that (1) microinjection of norepinephine into the CNTS of rabbit could significantly attenuate the frequency of renal nerve discharge, and at the same time decrease markedly the mean arterial pressure. (2) Microinjection of 0.3 nmol yohimbin into CNTS had no significant influence on FRND and MAP, but could attenuate and even reverse the effects of NE on FRND and MAP. These results suggest that microinjection of NE into CNTS may activate the alpha-adrenorecptor located in CNTS and secondarily produce a depressor effect by attenuating the activity of periphenal sympathetic nervous system.
Blood Pressure/drug effects ; Depression, Chemical ; Kidney/*innervation ; Microinjections ; Norepinephrine/*pharmacology ; Solitary Nucleus/*physiology ; Sympathetic Nervous System/drug effects ; Sympathetic Nervous System/*physiopathology ; Vasomotor System/physiopathology

The engineering of a functional blood vessel substitute has for a quarter of a century been a "holy grail" within the cardiovascular research community. Such a substitute must exhibit long term patency, and the critical issues in this area in many ways are influenced by biomechanics. One of the requirements is that it must be non-thrombogenic, which requires an "endothelial-like" inner lining. It also must have mechanical strength, i.e. a burst pressure, sufficient to operate at arterial pressures. Ideally, however, it must be more than this. It also must have viscoelastic properties that match those of the native vessel being replaced. Finally, if it is to be able to adapt to changing blood flow conditions, it must exhibit vasoactivity, a function which in and of itself can be viewed as biomechanical in nature. To achieve this requires having, as part of the construct, vascular smooth muscle cells, which are contractile in nature and oriented in a circumferential direction. Only if an engineered blood vessel substitute possesses all of these functional characteristics, can one say that the functionality exhibited by a native vessel is being mimicked.
Artificial Organs* ; Biomechanics ; Biomedical Engineering* ; Blood Vessels* ; Endothelium, Vascular/physiology ; Human ; Muscle, Smooth, Vascular/physiology ; Support, U.S. Gov't, Non-P.H.S. ; Thrombosis/etiology ; Vasomotor System/physiology

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

OBJECTIVETo explore the alterations in pulmonary arterial reactivity during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.

METHODSSixty-six male Sprague-Dawley rats were randomly divided into 2 groups: bleomycin (BLM) group and sham group. The rats in BLM group were received single intratracheal instillation of BLM (5 mg/kg), and the rats in sham group received equal volume of 0.9% normal saline (NS). The alterations in pulmonary arterial reactivity were measured by vascular tension detected technique, the pathomorphological changes in the wall of pulmonary arteries were displayed with Hematoxylin-Eosin (HE) staining, the degree of fibrosis in lung was revealed with Masson staining, and the mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery.

RESULTS(1) The contractile response to a- adrenoceptor agonist phenylephrine (PE), of pulmonary arteries both with remaining endothelium and with removing endothelium, from BLM-treated rats , was reduced significantly, compared with sham rats (P both < 0.05). (2) The relaxant response to the endothelially dependent vasodilator acetylcholine (Ach), of pulmonary arteries with remaining endothelium, from BLM-treated rats, was also reduced, compared with sham rats (P < 0.01). (3) In sham rats, the contractile response to (omega) -nitro-L-arginine methyl ester (L-NAME) plus PE, of pulmonary arteries with remaining endothelium, was enhanced, compared with that to PE alone (P < 0.01), while in BLM group, the contractile responses to L-NAME plus PE, of pulmonary arteries with remaining endothelium, was not different from that to PE alone (P > 0.05). (4) In BLM group, vascular endothelial cells lost. (5) In BLM group, the initial stage of fibrogenesis was observed in lungs, and the mean pulmonary arterial pressure increased, compared with that in sham group (P < 0.05).

CONCLUSIONThe abnormal responsibility of pulmonary arteries occurred during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.

Animals ; Familial Primary Pulmonary Hypertension ; Hypertension, Pulmonary ; complications ; physiopathology ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Fibrosis ; complications ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Vasomotor System ; physiology

ATP-sensitive potassium (K(ATP)) channels are widely distributed in vasculatures, and play an important role in the vascular tone regulation. The K(ATP) channels consist of 4 pore-forming inward rectifier K(+) channel (Kir) subunits and 4 regulatory sulfonylurea receptors (SUR). The major vascular isoform of K(ATP) channels is composed of Kir6.1/SUR2B, although low levels of other subunits are also present in vascular beds. The observation from transgenic mice and humans carrying Kir6.1/SUR2B channel mutations strongly supports that normal activity of the Kir6.1/SUR2B channel is critical for cardiovascular function. The Kir6.1/SUR2B channel is regulated by intracellular ATP and ADP. The channel is a common target of several vasodilators and vasoconstrictors. Endogenous vasopressors such as arginine vasopressin and α-adrenoceptor agonists stimulate protein kinase C (PKC) and inhibit the K(ATP) channels, while vasodilators such as β-adrenoceptor agonists and vasoactive intestinal polypeptide increase K(ATP) channel activity by activating the adenylate cyclase-cAMP-protein kinase A (PKA) pathway. PKC phosphorylates a cluster of 4 serine residues at C-terminus of Kir6.1, whereas PKA acts on Ser1387 in the nucleotide binding domain 2 of SUR2B. The Kir6.1/SUR2B channel is also inhibited by oxidants including reactive oxygen species allowing vascular regulation in oxidative stress. The molecular basis underlying such a channel inhibition is likely to be mediated by S-glutathionylation at a few cysteine residues, especially Cys176, in Kir6.1. Furthermore, the channel activity is augmented in endotoxemia or septic shock, as a result of the upregulation of Kir6.1/SUR2B expression. Activation of the nuclear factor-κB dependent transcriptional mechanism contributes to the Kir6.1/SUR2B channel upregulation by lipopolysaccharides and perhaps other toll-like receptor ligands as well. In this review, we summarize the vascular K(ATP) channel regulation under physiological and pathophysiological conditions, and discuss the importance of K(ATP) channel as a potentially useful target in the treatment and prevention of cardiovascular diseases.
ATP-Binding Cassette Transporters ; genetics ; physiology ; Animals ; Endotoxemia ; metabolism ; physiopathology ; Humans ; KATP Channels ; genetics ; physiology ; Mice ; Mice, Transgenic ; Muscle, Smooth, Vascular ; metabolism ; physiology ; Potassium Channels, Inwardly Rectifying ; genetics ; physiology ; Receptors, Drug ; genetics ; physiology ; Shock, Septic ; metabolism ; physiopathology ; Sulfonylurea Receptors ; Vasoconstriction ; physiology ; Vasodilation ; physiology ; Vasomotor System ; physiology

OBJECTIVETo study the relaxant effects of glycyrrhizinate and salvianolic acid B on rat portal vein in vitro.

METHODSHealthy female Wistar rats were canalized from hepatic artery, portal vein and hepatic vein in vitro. Remained blood in liver was eliminated with heparinized Krebs-Henseleit solution through hepatic artery, then the liver was isolated under infusing manner. Being constricted with phenylephrine and relaxed with acetylcholine, and infused with glycyrrhizinate or salvianolic acid B, the portal pressures of infused rat livers were consistently monitored by BL-420S physiological experiment system. The median effective concentration (EC50) of the two agents were analyzed with non-linear various slope regression using Prism-4 software.

RESULTSEC50 of glycyrrhizinate in relaxing the phenylephrine-contracted portal was 1.5556 x 10(-9) mol/L, suggesting one of the mechanism of action of diammonium glycyrhizinate for the treatment of portal hypertension was direct relaxation. Salvianolic acid B showed constrictive action on the phenylephrine-retracted portal vein, the EC50 was 1.4639 x 10(-9) mol/L, indicating that its indirect control action was took part in the portal hypertension therapy synergistically.

CONCLUSIONUnder the mode with both controlled-velocity and monitored pressure, glycyrrhizinate showed relaxation and salvianolic acid B showed constriction on portal pressure in vitro.

Animals ; Benzofurans ; pharmacology ; Blood Pressure ; drug effects ; Female ; Glycyrrhizic Acid ; pharmacology ; Hypertension, Portal ; physiopathology ; Phenylephrine ; pharmacology ; Portal Vein ; physiology ; Rats ; Rats, Wistar ; Vasoconstrictor Agents ; pharmacology ; Vasodilator Agents ; pharmacology ; Vasomotor System ; drug effects