Mechanism of thrombin-induced vasodilation in human coronary arterioles

2003 ◽  
Vol 284 (4) ◽  
pp. H1080-H1086 ◽  
Author(s):  
John J. Bosnjak ◽  
Ken Terata ◽  
Hiroto Miura ◽  
Atsushi Sato ◽  
Alfred C. Nicolosi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Right Atrial ◽  
Tetraethylammonium Chloride ◽  
Protein Activation ◽  
Protein Receptor ◽  
No Release ◽  
Before And After ◽  
Clotting Cascade ◽  
Tetrabutylammonium Chloride ◽  
Coronary Arterioles

Thrombin (Thromb), activated as part of the clotting cascade, dilates conduit arteries through an endothelial pertussis toxin (PTX)-sensitive G-protein receptor and releases nitric oxide (NO). Thromb also acts on downstream microvessels. Therefore, we examined whether Thromb dilates human coronary arterioles (HCA). HCA from right atrial appendages were constricted by 30–50% with endothelin-1. Dilation to Thromb (10−4–1 U/ml) was assessed before and after inhibitors with videomicroscopy. There was no tachyphylaxis to Thromb dilation (maximum dilation = 87.0%, ED50 = 1.49 × 10−2). Dilation to Thromb was abolished with either hirudin or denudation but was not affected by PTX. Neither N ω-nitro-l-arginine methyl ester ( n = 7), indomethacin ( n = 9),1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one ( n = 6), tetraethylammonium chloride ( n = 5), nor iberiotoxin ( n = 4) reduced dilation to Thromb. However, KCl (maximum dilation = 89 ± 5 vs. 20 ± 10%; P < 0.05; n = 7), tetrabutylammonium chloride (maximum dilation = 79 ± 7 vs. 21 ± 4%; P < 0.05; n = 5), and charybdotoxin (maximum dilation = 89 ± 4 vs. 10 ± 2%; P < 0.05; n = 4) attenuated dilation to Thromb. In contrast to animal models, Thromb-induced dilation in human arterioles is independent of Gi-protein activation and NO release. However, Thromb dilation is endothelium dependent, is maintained on consecutive applications, and involves activation of K+ channels. We speculate that an endothelium-derived hyperpolarizing factor contributes to Thromb-induced dilation in HCA.

Effect of inhibition of nitric oxide synthesis on the diaphragmatic microvascular response to hypoxia

1996 ◽  
Vol 81 (4) ◽  
pp. 1633-1641 ◽  
Author(s):  
Michael E. Ward
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Ex Vivo ◽  
Severe Hypoxia ◽  
Nitric Oxide Synthesis ◽  
Moderate Hypoxia ◽  
Vessel Size ◽  
Microvascular Response ◽  
No Release ◽  
Before And After

Ward, Michael E. Effect of inhibition of nitric oxide synthesis on the diaphragmatic microvascular response to hypoxia. J. Appl. Physiol. 81(4): 1633–1641, 1996.—The purpose of this study was to determine the effect of inhibition of nitric oxide (NO) release on the diaphragmatic microvascular responses to hypoxia. In α-chloralose-anesthetized mongrel dogs, the microcirculation of the vascularly isolated ex vivo left hemidiaphragm was studied by intravital microscopy. The diaphragm was pump perfused with blood diverted from the femoral artery through a series of membrane oxygenators. The responses to supramaximal concentrations of sodium nitroprusside, moderate hypoxia (phrenic venous [Formula: see text] 27 Torr), and severe hypoxia (phrenic venous [Formula: see text] 15 Torr) were recorded before and after an infusion of N G-nitro-l-arginine (l-NNA; 6 × 10−4 M) into the phrenic circulation for 20 min. Under control conditions, diaphragmatic blood flow was 12.4 ± 1.1 ml ⋅ min−1 ⋅ 100 g−1. Diaphragmatic blood flows recorded during moderate and severe hypoxia were 15.6 ± 1.2 and 24.3 ± 1.5 ml ⋅ min−1 ⋅ 100 g−1, respectively ( P < 0.05 for both compared with control values). Treatment withl-NNA reduced diaphragmatic blood flow to 9.6 ± 0.8 ml ⋅ min−1 ⋅ 100 g−1 under control conditions ( P < 0.05) and caused arteriolar vasoconstriction to a degree that was dependent on vessel size (i.e., larger vessels constricted more than smaller vessels).l-NNA eliminated the increase in blood flow during moderate hypoxia and inhibited arteriolar dilation by an amount that was related to vessel size (i.e., dilation of larger vessels was inhibited more than that of smaller vessels). Inhibition of NO synthesis had no effect on the increase in diaphragmatic blood flow (23.6 ± 1.9 ml ⋅ min−1 ⋅ 100 g−1; P > 0.05 compared with that during severe hypoxia before treatment withl-NNA) or arteriolar diameters during severe hypoxia. NO release plays a role in the diaphragmatic vascular response to hypoxia, but this role is limited to dilation of larger arterioles during hypoxia of moderate severity.

scholarly journals Effects of Electroacupuncture Stimulation at “Zusanli” Acupoint on Hepatic NO Release and Blood Perfusion in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shu-you Wang ◽  
Dong Zhang ◽  
Li-mei Tang ◽  
Shun-yue Li ◽  
Mei Wen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Acid ◽  
Liver Tissue ◽  
Blood Perfusion ◽  
Laser Speckle ◽  
Control Group ◽  
No Release ◽  
Before And After ◽  
Zusanli Acupoint ◽  
Oxide Synthase

The study is to observe the influence of electroacupuncture (EA) stimulation at “Zusanli” (ST36) on the release of nitric oxide (NO) and blood perfusion (BP) in the liver and further explore whether the hepatic blood perfusion (HBP) changes were regulated by EA ST36 induced NO in nitric oxide synthase inhibited mice. The HBP change of the mice was detected by laser speckle perfusion imaging (LSPI) before and after being given interventions, and the NO in liver tissue was detected by nitric acid reductase in each group. The NO levels and HBP in the L-NAME group were significantly lower than those in the control group (P<0.01). The NO level and HBP increase in EA group were significantly higher than those in control group (P<0.05). The NO level in the L-NAME EA group was slightly higher than that in the L-NAME group. The HBP increase in the L-NAME EA group was not statistically significant. These results showed that EA could accelerate the synthesis of NO and thereby increase HBP via vasodilation in liver tissue.

Abstract 1141: Adaptation of Coronary Arteriolar Dilations to The Simultaneous Presence of Obesity and Hypertension: Role of Increased Nitric Oxide Sensitivity

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Zsolt Bagi ◽  
Tibor Fulop ◽  
Eva Jebelovszki ◽  
Nora Erdei ◽  
Tamas Szerafin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Right Atrial ◽  
Simultaneous Presence ◽  
No Donor ◽  
Hypertensive Patients ◽  
Increased Sensitivity ◽  
Peripheral Arterial ◽  
The Right ◽  
Coronary Arterioles

Increased body weight and elevated blood pressure could lead to the development of hyperdynamic circulation requiring increased coronary blood flow. Thus, we aimed to characterize the effects of simultaneous presence of obesity and hypertension on the dilator function of human coronary arterioles. Agonist-induced dilations were assessed in pressurized coronary arterioles isolated from the right atrial appendages of patients (N=38), that underwent cardiac surgery. There were no significant differences in bradykinin (BK)-induced and the nitric oxide (NO)-donor, sodium-nitroprusside (SNP)-evoked dilations of coronary arterioles between normotensive and hypertensive lean patients. In contrast, in the obese, normotensive patients BK- and SNP-induced dilations were reduced (BK, 10 −7 M, lean:90±4%, obese:64±7%; SNP, 10 −6 M, lean:89±7%, obese:76±5%), whereas in the obese, hypertensive patients BK- and SNP-induced dilations were significantly enhanced, when compared to lean subjects (BK, 10 −7 M, lean:71±7%, obese:85±3%; SNP, 10 −6 M, lean:60±6%, obese:83±2%). Correspondingly, in hypertensive individuals, but not in those of normotensives, a positive correlation was found between body mass index (BMI) and bradykinin-induced ( P =0.03, r=0.46), and also SNP-evoked ( P< 0.03, r=0.44) coronary dilations. To correlate coronary responses to those of peripheral vessels, in an additional 55 hypertensive patients flow-mediated (FMD) and nitroglycerin (NTG)-induced dilations were assessed by high-resolution ultrasound. In obese, hypertensive individuals both FMD and NTG-induced dilations were significantly greater (FMD:6.2±0.7%, NTG:17.2±0.9%), than in lean hypertensive patients (FMD:3.7±0.6%, NTG:13.6±1.1%). Correspondingly, both FMD and NTG-induced dilations were positively correlated with BMI, ( P =0.02, r=0.31, P =0.03, r=0.29, respectively). These findings are the first to show that in humans obesity may lead to activation of an adaptive vascular mechanisms in hypertension, such as an increased sensitivity to NO, enhancing the dilator function of coronary and peripheral arterial vessels.

scholarly journals Electroacupuncture Zusanli (ST36) on Release of Nitric Oxide in the Gracile Nucleus and Improvement of Sensory Neuropathies in Zucker Diabetic Fatty Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Pei-Jing Rong ◽  
Sheng-Xing Ma
Keyword(s):  
Nitric Oxide ◽  
Microdialysis Probe ◽  
Thermal Nociception ◽  
Gracile Nucleus ◽  
Zucker Diabetic Fatty Rats ◽  
No Release ◽  
Before And After ◽  
Zdf Rats ◽  
Nitrate And Nitrite ◽  
Thermal Stimuli

The purpose of these studies was to examine the effects of electroacupuncture (EA) Zusanli (ST36) on release of nitric oxide (NO) in the gracile nucleus (GN) and determine if functional neuropathic changes were modified by EA ST36-induced NO in the nucleus in Zucker diabetic fatty (ZDF) rats. The foot withdrawal responses to mechanical, thermal and cold stimuli were measured before and after EA stimulation. A microdialysis probe was implanted in the GN and dialysate samples were collected 20 min before, during and after EA ST36. Total nitrate and nitrite () concentrations in the samples were quantified by using chemiluminescence. The baseline dialysate concentrations in the GN were decreased in ZDF rats compared to lean control (LC) rats (). In ZDF rats, dialysate releases in the GN were markedly increased during EA ST36, whereas in LC rats, the releases were moderately enhanced at 20–40 min after EA ST36. The withdrawal latencies to mechanical, cold and thermal stimuli were significantly improved 20 min after EA ST36 both in LC and ZDF rats, but not altered by non-acupoint stimulation. The withdrawal latencies to EA ST36 were further potentiated by 3-morpholinyl-sydnoneimine and inhibited by NG-Propyl-L-arginine infused into the GN in ZDF rats (). These results show that EA ST36 increases NO release in the GN, and NO in the nucleus modifies withdrawal latencies to mechanical, cold, and thermal nociception stimuli. Data suggest that EA ST36 induces NO release in the GN, which contributes to improvement of sensory neuropathies in rats.

The Effect on Health of Some Cardiovascular Risk Factors

2017 ◽  
Vol 68 (10) ◽  
pp. 2237-2242
Author(s):  
Germaine Savoiu Balint ◽  
Mihaiela Andoni ◽  
Ramona Amina Popovici ◽  
Laura Cristina Rusu ◽  
Ioana Citu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Vascular Wall ◽  
Dose Effect ◽  
Organ Bath ◽  
Before And After ◽  
Specific Receptors ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Relaxing Response

Arterial endothelium produces a large ramge of active factors which are indispensable for modulation of vasomotor tone and maintenance of vascular wall integrity. From these factors, nitric oxide (NO), wich is released by the endothelial cells as a response to acetylcholine or adenosine action on specific receptors, plays an important role.NO is the result of oxidation process of L-arginine into L-citrulline, under the action of endothelial nitric oxide synthase (NOSe), wich is activated by intracelluar Ca2+ - calmodulin complex . Our study, performed in isolated organ bath, analyzed vascular reactivity of 12 guinea pigs� thoracic aorta rings. After phenylephrine -PHE 10-5 mol/L precontraction, the dose-effect curves for acetylcoline � ACH, adenosine 5� phosphate - 5�ADP and sodium nitroprusside � SNP were determined, before and after incubation of preparation, for 1 hour, with 5% hydrosoluble cigarettes smoke extract (CSE). Statistic analysis, performed with the use of t pair test and ANOVA parametric test, showed that incubation of vascular preparation with 5% CSE has increased the contractile response to PHE 10-5 mol/L (p[0.05), has reduced the endothelium-dependent relaxing response to ATP 10-5 mol/L (p[0.001) and 5�ADP 10-5 molo/L (p[0.001), but has not significantly modified the endothelium-independent relaxing response to SNP 10-5 mol/L (p=0.05). As a conclusion, vascular rings incubation with 5% CSE induced a decrease of endothelium NO synthesis under the action of AXH and 5�ADP, but did not change the smooth muscle fiber respomse in the presence of NO released by SNP.

Decrease in ambient [Cl-] stimulates nitric oxide release from cultured rat mesangial cells

1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Ionic Composition ◽  
Juxtaglomerular Apparatus ◽  
Cytosolic Calcium ◽  
No Synthase ◽  
Tubuloglomerular Feedback ◽  
No Production ◽  
Rapid Reduction ◽  
No Release

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

scholarly journals Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants

2011 ◽  
Vol 301 (3) ◽  
pp. R763-R768 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
Oxidant Stress ◽  
Microvascular Dysfunction ◽  
Local Skin ◽  
Cutaneous Vasodilation ◽  
Before And After ◽  
Atorvastatin Therapy ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ≪ngname≫ was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVCmax, P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVCmax, P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVCmax, P < 0.001) or combined with arginase inhibition (96 ± 3% CVCmax, P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVCmax, both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVCmax, P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVCmax, P > 0.05) or combined with arginase inhibition (67 ± 4% CVCmax, P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.

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