Role of Endothelium-Derived Relaxing Factor as a Cardioprotective Agent in Myocardial Ischemia

2015 ◽  
pp. 190-197 ◽  
Author(s):  
Allan M. Lefer ◽  
Phillip S. Tsao ◽  
Gerald Johnson
Keyword(s):  
Myocardial Ischemia ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Why is a new journal dedicated to vascular biology required?

2018 ◽  
Author(s):  
Paolo Madeddu
Keyword(s):  
Myocardial Ischemia ◽  
Tumor Growth ◽  
Vascular Tone ◽  
50Th Anniversary ◽  
Vascular Biology ◽  
Active Process ◽  
Master Regulators ◽  
Relaxing Factor ◽  
Tissue Healing ◽  
Endothelium Derived Relaxing Factor

The year 2018 marked the 110th anniversary of Goldmann’s discovery that vascularization is an active process in tissues1 and the 50th anniversary of the concomitant reports from Greenblatt and Shubik2 and Ehrmann and Knoth3 that soluble morphogenic factors are required for cancer angiogenesis. Many other radically transformative paradigms have been introduced in the last decades. To name a few, the molecular search for the identity of master regulators of vascular tone led to the discovery of the Endothelium-Derived Relaxing Factor (EDRF; i.e., NO4), while clinically inspired investigations led to the recognition of the pathophysiological relevance of neoangiogenesis in cancer and tissue healing. This brought about the proposal of blocking angiogenesis to halt tumor growth and stimulating angiogenesis to treat myocardial ischemia and heart failure5-7.

Endothelium-derived relaxing factor in regulation of basal cardiopulmonary and renal function

1991 ◽  
Vol 261 (2) ◽  
pp. R323-R328 ◽  
Author(s):  
M. A. Perrella ◽  
F. L. Hildebrand ◽  
K. B. Margulies ◽  
J. C. Burnett
Keyword(s):  
Renal Function ◽  
Competitive Inhibitor ◽  
Vehicle Group ◽  
Relaxing Factor ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Renal Vascular ◽  
Renal Responses

The endothelium has emerged as an important modulator of vascular tone by producing both vasodilating and vasoconstricting substances. In vitro studies have demonstrated that endothelial cells produce endothelium-derived relaxing factor (EDRF), which promotes vasodilation via the stimulation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). However, the role of EDRF in the basal regulation of cardiopulmonary and renal function is not well defined. The present study was therefore designed to assess the function of EDRF by studying two groups of normal anesthetized dogs, of which one received a competitive inhibitor to EDRF generation, NG-monomethyl-L-arginine (L-NMMA; 50 micrograms.kg-1.min-1 iv), and the other received a vehicle. The L-NMMA infusion produced no significant increase in mean arterial pressure but marked increases in systemic, pulmonary, and renal vascular resistances compared with the vehicle group. Although renal blood flow decreased with L-NMMA, no changes were observed in glomerular filtration rate or sodium excretion. Associated with the cardiopulmonary and renal responses with L-NMMA was a modest increase in plasma endothelin (7.9 +/- 1.3 to 10.2 +/- 1.8 pg/ml, P less than 0.05), an endothelium-derived vasoconstrictor. No alteration was observed in plasma or urinary cGMP with EDRF inhibition. These cardiopulmonary and renal responses with L-NMMA may be attributed not only to EDRF inhibition but to an imbalance between endothelium-derived relaxing and contracting factors.

Role of Endothelium -Derived Relaxing Factor in the Pathogenesis of Coronary Artery Spasm and Its Relationship with Ethanol

1992 ◽  
Vol 22 (5) ◽  
pp. 768
Author(s):  
Jung Don Seo ◽  
Jae Kwan Song ◽  
Cheol Ho Kim ◽  
Dae-Won Sohn ◽  
Byung Hee Oh ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Spasm ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling

1993 ◽  
Vol 74 (3) ◽  
pp. 1061-1065 ◽  
Author(s):  
L. Zhao ◽  
D. E. Crawley ◽  
J. M. Hughes ◽  
T. W. Evans ◽  
R. J. Winter
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Pulmonary Vascular Remodeling ◽  
Relaxing Factor ◽  
Pulmonary Vasoconstriction ◽  
O2 Concentration ◽  
Pulmonary Arterial ◽  
Endothelium Derived Relaxing Factor

We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood-perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2–5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of prostaglandins and endothelium-derived relaxing factor on the renal response to acetylcholine

1991 ◽  
Vol 260 (1) ◽  
pp. F145-F149 ◽  
Author(s):  
M. G. Salom ◽  
V. Lahera ◽  
J. C. Romero
Keyword(s):  
Urine Volume ◽  
Urinary Sodium Excretion ◽  
Diuretic Effect ◽  
Simultaneous Administration ◽  
Relaxing Factor ◽  
Blocking Effects ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Renal Responses

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.

Role of EDRF/NO in parasympathetic coronary vasodilation following carotid chemoreflex activation in conscious dogs

1994 ◽  
Vol 267 (2) ◽  
pp. H605-H613 ◽  
Author(s):  
W. Shen ◽  
M. Ochoa ◽  
X. Xu ◽  
J. Wang ◽  
T. H. Hintze
Keyword(s):  
Vagus Nerve ◽  
Conscious Dogs ◽  
Coronary Resistance ◽  
Vascular Response ◽  
Coronary Vasodilation ◽  
Relaxing Factor ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Stimulation Of

The role of endothelium-derived relaxing factor (EDRF) in parasympathetic coronary vasodilation following carotid chemoreflex activation induced by nicotine in conscious dogs and stimulation of the vagus nerve in anesthetized dogs was studied. Injection of nicotine (11 +/- 4 micrograms) into the carotid artery increased coronary blood flow (CBF) by 126 +/- 16% from 28 +/- 3 ml/min and reduced late diastolic coronary resistance (LDCR) by 43 +/- 4% from 3.58 +/- 0.52 mmHg.ml-1.min, accompanied by a significant increase in mean arterial pressure and a decrease in heart rate (all P < 0.01). Pacing and propranolol did not change the coronary vascular response to chemoreflex activation. There were still increases in CBF by 113 +/- 17% from 29 +/- 3 ml/min and decreases in LDCR by 41 +/- 5% from 3.13 +/- 0.52 mmHg.ml-1.min (all P < 0.01). After infusion of N omega-nitro-L-arginine (L-NNA) (30 mg/kg), the increase in CBF following chemoreflex activation was only 23 +/- 3% from 37 +/- 3 ml/min, and the fall in LDCR was 19 +/- 3% from 3.09 +/- 0.51 mmHg.ml-1.min. Stimulation of the vagus nerve showed a relationship between stimulation frequency and coronary vasodilation that was significantly inhibited by L-NNA. Thus EDRF plays an important role in mediating parasympathetic coronary vasodilation during chemoreflex activation and perhaps during many reflexes that cause vagal cholinergic vasodilation in the heart.

Role of Endothelium-Derived Relaxing Factor in Endothelin-Induced Renal Vasoconstriction

1991 ◽  
Vol 17 ◽  
pp. S169-171 ◽  
Author(s):  
Yasunobu Hirata ◽  
Hiroaki Matsuoka ◽  
Kenjiro Kimura ◽  
Tokuichiro Sugimoto ◽  
Hiroshi Hayakawa ◽  
...  
Keyword(s):  
Renal Vasoconstriction ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation

1992 ◽  
Vol 262 (5) ◽  
pp. H1579-H1584 ◽  
Author(s):  
T. P. Broten ◽  
J. K. Miyashiro ◽  
S. Moncada ◽  
E. O. Feigl
Keyword(s):  
Vagal Stimulation ◽  
Specific Inhibitor ◽  
Coronary Vasodilation ◽  
Relaxing Factor ◽  
Inhibit Prostaglandin Synthesis ◽  
Constant Rate ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Alpha Chloralose

Vasodilation following the infusion of acetylcholine is due to the release of endothelium-derived relaxing factor (EDRF). However, the role of EDRF in neurogenic coronary vasodilation, when acetylcholine is released outside the vessel at the adventitial-medial junction, has not been established. The action of EDRF in parasympathetic coronary vasodilation was tested in the present study using a specific inhibitor of EDRF synthesis, nitro-L-arginine methyl ester (L-NAME). Experiments were conducted on closed-chest, alpha-chloralose-anesthetized dogs with the heart paced at a constant rate. Phentolamine and propranolol were administered to block alpha- and beta-adrenergic receptors, and ibuprofen was given to inhibit prostaglandin synthesis. Intracoronary infusion of L-NAME decreased the coronary vasodilation in response to intracoronary acetylcholine or vagal stimulation. The coronary response to the endothelium-independent vasodilator nitroglycerin was unaffected by L-NAME. These data demonstrate that L-NAME specifically inhibits coronary vasodilation caused by acetylcholine and vagal stimulation, indicating that parasympathetic coronary vasodilation is dependent on EDRF.

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