Effects of estrogen in vivo on coronary vascular resistance in perfused rabbit hearts

1995 ◽  
Vol 269 (6) ◽  
pp. R1333-R1338 ◽  
Author(s):  
G. I. Gorodeski ◽  
T. Yang ◽  
M. N. Levy ◽  
J. Goldfarb ◽  
W. H. Utian
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Coronary Vascular Resistance ◽  
Intravenous Injections ◽  
Oxide Synthase ◽  
Perfused Hearts

Estrogen or its vehicle was given daily to three groups of ovariectomized rabbits for various lengths of time, after which coronary flow was measured in their isolated perfused hearts. In one group, intramuscular injections of estrogen (40 micrograms/kg) for 7 or 14 days increased coronary flow by 40-50% (P < 0.05). In rabbits given estrogen intramuscularly for 7 days, the coronary flow returned to the basal level within 7 days after the estrogen injections were discontinued. In a second group of animals, intravenous injections of estrogen (10 micrograms/kg) for 4 days increased the coronary flow by 45% (P < 0.01). In a third group, we administered the estrogen transdermally for 4 days, and we measured the plasma estrogen levels at the end of this period. The coronary flow in this group was increased by 52% (P < 0.001), and the plasma estrogen levels ranged from 39 to 800 pg/ml. In all groups of experiments, the increments in coronary flow evoked by estrogen were virtually abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase. We conclude that estrogen regulates coronary blood flow, in part by upregulating nitric oxide synthase in the coronary vasculature.

scholarly journals The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

2017 ◽  
Vol 313 (3) ◽  
pp. H578-H583 ◽  
Author(s):  
Sitara G. Khan ◽  
Narbeh Melikian ◽  
Husain Shabeeh ◽  
Ana R. Cabaco ◽  
Katherine Martin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Mental Stress ◽  
Coronary Flow ◽  
Neuronal Nitric Oxide Synthase ◽  
Coronary Artery Diameter ◽  
Oxide Synthase

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/ .

Abstract 1138: Endogenous Adipocyte-Derived Factors Diminish Coronary Endothelial-Dependent Vasodilation Via Inhibition Of Nitric Oxide Synthase

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gregory A Payne ◽  
Lena Borbouse ◽  
Gregory M Dick ◽  
Johnathan D Tune
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Dependent Manner ◽  
Pericardial Adipose Tissue ◽  
Oxide Synthase

Adipocytokines may be the molecular link between obesity and vascular disease; however, effects of these factors on coronary vascular function have not been delineated. Accordingly, this study was designed to examine mechanisms by which endogenous adipocyte-derived factors impair coronary endothelial-dependent vasodilation in vivo . Experiments were conducted in open-chest anesthetized dogs (n = 16) before and during treatment with endogenous adipocyte-derived factors. Phosphate buffered saline was conditioned in a shaking water bath with parietal pericardial adipose tissue (3 g/ml) for 30 min at 37°C. The conditioned buffer was then filtered (0.2 μm) and infused directly into the coronary circulation (0.3 ml/min). Conditioned buffer did not significantly affect baseline coronary blood flow (0.50 ± 0.01 vs. 0.61 ± 0.05 ml/min/g, p = 0.68), mean arterial pressure (103 ± 6 vs. 96 ± 9 mmHg, p = 0.74), or heart rate (87 ± 13 vs. 110 ± 24 beats/min, p = 0.44). Conditioned buffer had no effect on responses to intracoronary angiotensin II (2.5 – 750 ng; 74 vs. 70% vasoconstriction). Under control conditions, bradykinin (0.03 – 3 μg/min) increased coronary blood flow (303 ± 65%) to 2.02 ± 0.31 ml/min/g in a dose-dependent manner. Conditioned buffer attenuated maximum bradykinin vasodilation to 1.64 ± 0.26 ml/min/g (167 ± 33% increase; p < 0.05). This decrease in endothelial-dependent dilation was not due to increases in superoxide production, as administration of the superoxide dismutase mimetic Tempol (10 mg/min, ic) did not improve bradykinin vasodilation (120 ± 27% increase; p < 0.05). Inhibition of nitric oxide synthase with L-NAME (150 μg/min, ic) reduced maximum bradykinin vasodilation to 0.93 ± 0.04 ml/min/g (p < 0.05) and endogenous adipocyte-derived factors had no further inhibitory effect (0.82 ± 0.09 ml/min/g, p = 0.24). These data indicate that endogenous adipocyte-derived factors diminish endothelial-dependent coronary vasodilation via inhibition of nitric oxide synthase rather than a reduction in nitric oxide bioavailability by superoxide. Our findings importantly link endogenous adipocyte-derived factors with pro-atherogenic coronary vascular dysfunction in vivo .

scholarly journals 106 Role of neuronal vs endothelial nitric oxide synthase in the coronary blood flow response to pacing

Heart ◽  
2012 ◽  
Vol 98 (Suppl 1) ◽  
pp. A60.2-A61
Author(s):  
H Shabeeh ◽  
N Melikian ◽  
R Dworakowski ◽  
B Casadei ◽  
P Chowienczyk ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Endothelial Nitric Oxide Synthase ◽  
Blood Flow Response ◽  
Flow Response ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Endothelial nitric oxide synthase genotype modulates the improvement of coronary blood flow by pravastatin: a placebo-controlled PET study

2002 ◽  
Vol 80 (12) ◽  
pp. 802-807 ◽  
Author(s):  
Tarja A. Kunnas ◽  
Terho Lehtimäki ◽  
Reijo Laaksonen ◽  
Erkki Ilveskoski ◽  
Tuula Janatuinen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

2380Mechanisms of myocardial ischemia during exercise in microvascular angina

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Rahman ◽  
M Ryan ◽  
M Lumley ◽  
H McConkey ◽  
F Khan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Myocardial Perfusion ◽  
Coronary Blood Flow ◽  
Coronary Perfusion ◽  
Fractional Flow ◽  
Microvascular Angina ◽  
Flow Reserve ◽  
Oxide Synthase

Abstract Background Coronary microvascular dysfunction (MVD) is defined by impaired flow augmentation in response to a vasodilator, the pathophysiological basis of which is unclear. This study sought to address two major gaps in our understanding of MVD: firstly, whether diminished flow reserve is due to structural changes within the microvasculature or potentially reversible dysfunction and secondly to unravel the mechanism of exercise-induced ischemia in the absence of obstructive disease. Methods Simultaneous intracoronary pressure and flow velocity recordings were made in the left anterior descending artery of patients with angina and no obstructive epicardial disease (Fractional Flow Reserve >0.80). Measurements were made at rest, during adenosine-mediated hyperaemia and supine bicycle exercise. Wave intensity analysis was used to quantify waves that accelerate and decelerate coronary blood flow, coronary perfusion efficiency being defined as the proportion of total wave energy that accelerates blood flow. Patients were prospectively classified into MVD (coronary flow reserve <2.5) and controls with researchers blinded to the classification throughout the protocol. Myocardial perfusion and vascular function were assessed by 3T cardiac MRI and venous occlusion plethysmography with forearm blood flow (FBF) assessment during serial infusions of acetylcholine, adenosine and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Results 78 patients were enrolled (42 patients had MVD and 36 were controls), with no differences in cardiovascular risk factors between groups. The MVD group had elevated coronary blood flow (21.3±6.4 vs. 15.1±4.5cm s–1; p<0.001) and global myocardial perfusion (1.36±0.37 vs. 1.13±0.22ml/min/g; p=0.01) at rest. Maximum coronary and myocardial blood flow during hyperaemia was similar in both groups. During exercise, MVD patients achieved similar peak flow (30.5±10.0 vs. 26.3±7.7cm s–1; p=0.07) despite a higher rate-pressure product (20777±5205 vs. 17450±4710bpm.mmHg; p=0.01). Coronary perfusion efficiency, decreased with exercise in the MVD group (61±11% vs. 44±10% p<0.001) but was unchanged in controls. On MRI, MVD had lower hyperaemic endo-epicardial perfusion ratio than controls (0.94±0.08 vs. 1.04±0.13; p=0.001). Augmentation of FBF with acetylcholine was attenuated in MVD patients compared to controls (p=0.02) but the response to adenosine was similar (p=0.13). Infusion of L-NMMA caused a significantly greater reduction in FBF in MVD patients compared to controls (p<0.001). Exercise Physiology in MVD Conclusion Impaired flow reserve in MVD represents a dysfunctional state, characterised by inappropriately elevated resting flow due to increased nitric-oxide synthase mediated vasodilatation. There is abnormal flow distribution in the myocardium predisposing to subendocardial ischaemia, associated with and exacerbated by impaired cardiac-coronary coupling during exercise. These novel findings may represent distinct therapeutic targets. Acknowledgement/Funding British Heart Foundation

Upregulation of neuronal nitric oxide synthase in skeletal muscle by swim training

2000 ◽  
Vol 279 (4) ◽  
pp. H1757-H1766 ◽  
Author(s):  
Rabelais Tatchum-Talom ◽  
Richard Schulz ◽  
J. Robert McNeill ◽  
Fadi H. Khadour
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Similar Degree ◽  
Mesenteric Arterial Bed ◽  
Neuronal Nos ◽  
Oxide Synthase

Exercise enhances cardiac output and blood flow to working skeletal muscles but decreases visceral perfusion. The alterations in nitric oxide synthase (NOS) activity and/or expression of the cardiopulmonary, skeletal muscle, and visceral organs induced by swim training are unknown. In sedentary and swim-trained rats (60 min twice/day for 3–4 wk), we studied the alterations in NOS in different tissues along with hindquarter vasoreactivity in vivo during rest and mesenteric vascular bed reactivity in vitro. Hindquarter blood flow and conductance were reduced by norepinephrine in both groups to a similar degree, whereas N G-nitro-l-arginine methyl ester reduced both indexes to a greater extent in swim-trained rats. Vasodilator responses to ACh, but not bradykinin or S-nitroso- N-acetyl-penicillamine, were increased in swim-trained rats. Ca2+-dependent NOS activity was enhanced in the hindquarter skeletal muscle, lung, aorta, and atria of swim-trained rats together with increased expression of neuronal NOS in the hindquarter skeletal muscle and endothelial NOS in the cardiopulmonary organs. Mesenteric arterial bed vasoreactivity was unaltered by swim training. Physiological adaptations to swim training are characterized by enhanced hindquarter ACh-induced vasodilation with upregulation of neuronal NOS in skeletal muscle and endothelial NOS in the lung, atria, and aorta.

scholarly journals Effects of Neuronal Nitric Oxide Synthase on Human Coronary Artery Diameter and Blood Flow In Vivo

Circulation ◽  
2009 ◽  
Vol 119 (20) ◽  
pp. 2656-2662 ◽  
Author(s):  
Michael Seddon ◽  
Narbeh Melikian ◽  
Rafal Dworakowski ◽  
Husain Shabeeh ◽  
Benyu Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Human Coronary Artery ◽  
Coronary Artery Diameter ◽  
Oxide Synthase

scholarly journals Intracoronary Genistein Acutely Increases Coronary Blood Flow in Anesthetized Pigs through β-Adrenergic Mediated Nitric Oxide Release and Estrogenic Receptors

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2678-2687 ◽  
Author(s):  
Elena Grossini ◽  
Claudio Molinari ◽  
David A. S. G. Mary ◽  
Francesca Uberti ◽  
Philippe Primo Caimmi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Adrenergic Receptors ◽  
Primary Effect ◽  
No Production ◽  
Concomitant Treatment ◽  
Vascular Effects ◽  
Oxide Synthase

Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system, and nitric oxide (NO). The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intracoronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs, blockade of cholinergic receptors (iv atropine; five pigs) and α-adrenergic receptors (iv phentolamine; five pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of β2-adrenergic receptors (iv butoxamine; five pigs), nitric oxide synthase (intracoronary Nω-nitro-l-arginine methyl ester; five pigs) and estrogenic receptors (ERs; ERα/ERβ; intracoronary fulvestrant; five pigs). In porcine aortic endothelial cells, genistein induced the phosphorylation of endothelial nitric oxide synthase and NO production through ERK 1/2, Akt, and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ERα/ERβ and the release of NO through vasodilatory β2-adrenoreceptor effects.

Sign in / Sign up

Export Citation Format

Share Document