Pharmacological differentiation of epithelium-derived relaxing factor from nitric oxide

1990 ◽  
Vol 69 (2) ◽  
pp. 665-670 ◽  
Author(s):  
M. Munakata ◽  
Y. Masaki ◽  
I. Sakuma ◽  
H. Ukita ◽  
Y. Otsuka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Vascular System ◽  
Serosal Side ◽  
Epithelial Surface ◽  
Relaxing Factor ◽  
Complete Relaxation ◽  
Osmotic Stimulus ◽  
Endothelium Dependent Relaxation

We examined the possibility that nitric oxide is one of the epithelium-derived relaxing factors in guinea pig airways. First we studied whether nitric oxide could relax isolated tracheal strips, and then we examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system [hemoglobin, methylene blue, and NG-monomethyl-L-arginine (L-NMMA)] on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations. Mannitol (160 mM in Krebs-Henseleit solution) applied to the epithelial surface was used as an osmotic stimulus to induce EpDR after carbachol-induced contraction (2 microM, serosal side). Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR (P less than 0.05), but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that, although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR.

Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

1989 ◽  
Vol 257 (6) ◽  
pp. H1910-H1916 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Sodium Nitroprusside ◽  
Femoral Vein ◽  
Pulmonary Veins ◽  
Chemical Properties ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries

2001 ◽  
Vol 280 (1) ◽  
pp. H76-H82 ◽  
Author(s):  
Qiong Yang ◽  
Elizabeth Scalbert ◽  
Philippe Delagrange ◽  
Paul M. Vanhoutte ◽  
Stephen T. O'Rourke
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Coronary Arteries ◽  
Isometric Tension ◽  
Maximal Response ◽  
Melatonin Receptor ◽  
Vasomotor Tone ◽  
Vasoconstrictor Response ◽  
Coronary Vasomotor Tone

The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10−10-10−5 M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10−9-10−5 M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10−7 M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A2 analog U-46619 (10−10-10−7 M). The melatonin-receptor antagonist S-20928 (10−6 M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M), methylene blue (10−5 M), or NG -nitro-l-arginine (3 × 10−5 M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10−7 M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10−9-10−5 M) but not by isoproterenol (10−9-10−5 M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium.

Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations

1998 ◽  
Vol 7 (2) ◽  
pp. 131-140 ◽  
Author(s):  
J McHugh ◽  
DJ Cheek
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular System ◽  
Biological Activities ◽  
Vascular Diseases ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Physical Stimuli ◽  
Artery Disease

The endothelial cells of the vascular system are responsible for many biological activities that maintain vascular homeostasis. Responding to a variety of chemical and physical stimuli, the endothelium elaborates a host of vasoactive agents. One of these agents, endothelium-derived relaxing factor, now accepted as nitric oxide, influences both cellular constituents of the blood and vascular smooth muscle. A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G. Acting by this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation. Derangements in endothelial production of nitric oxide are implicated as both cause and consequence of vascular diseases, including hypertension, atherosclerosis, and coronary artery disease.

Hyperkalemia alters EDHF-mediated hyperpolarization and relaxation in coronary arteries

1996 ◽  
Vol 271 (2) ◽  
pp. H760-H767 ◽  
Author(s):  
G. W. He ◽  
C. Q. Yang ◽  
W. F. Graier ◽  
J. A. Yang
Keyword(s):  
Nitric Oxide ◽  
Cardiac Surgery ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Organ Preservation ◽  
Maximal Response ◽  
K Channels ◽  
Porcine Coronary Artery ◽  
Preservation Solutions ◽  
Endothelium Dependent Relaxation

Hyperkalemic solutions are widely used to preserve organs for transplantation and for cardiac surgery. The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through a non-nitric oxide (NO) pathway, since preliminary studies have shown that the NO pathway may not be affected. Porcine coronary artery rings were studied in organ chambers. After incubation with 20 or 50 mM K+ for 1 h, the indomethacin- and NG-nitro-L-arginine+ (L-NNA)-resistant relaxation induced by A23187 or bradykinin, which could be further inhibited by tetraethylammonium but not glibenclamide, was significantly reduced. Incubation with hyperkalemia also significantly increased the concentration eliciting 50% of the maximal response to A23187 and bradykinin. A23187-induced hyperpolarization of the membrane potential was significantly reduced by hyperkalemic incubation. However, 1-h incubation with hyperkalemia does not affect the endothelial Ca2+ concentration. We conclude that exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant endothelium-dependent relaxation and endothelium-dependent hyperpolarization. This reduction in the relaxation and hyperpolarization is related to the endothelium-derived hyperpolarizing factor by affecting its effect on the smooth muscle cell, probably through partially depolarizing the membrane, and the Ca2(+)- activated K+ channels rather than by affecting its biosynthesis and/or release in the endothelial cell. Our study may suggest a new mechanism for coronary dysfunction after exposure to hyperkalemic cardioplegia and organ preservation solutions.

Dirofilaria immitis: heartworm infection alters pulmonary artery endothelial cell behavior

1997 ◽  
Vol 82 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Maria Mupanomunda ◽  
Jeffrey F. Williams ◽  
Charles D. Mackenzie ◽  
Lana Kaiser
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Dirofilaria Immitis ◽  
Cell Behavior ◽  
A 23187 ◽  
Heartworm Infection ◽  
Endothelium Dependent Relaxation ◽  
Pulmonary Artery Endothelial Cell

Mupanomunda, Maria, Jeffrey F. Williams, Charles D. Mackenzie, and Lana Kaiser. Dirofilaria immitis:heartworm infection alters pulmonary artery endothelial cell behavior. J. Appl. Physiol. 82(2): 389–398, 1997.—The pathogenesis of filariasis has generally been attributed to either physical presence of the adult parasites or the host’s immune response to the parasites. However, the spectrum of filariasis cannot be entirely explained by these causes, and other mechanisms must be operative. It is now evident that factors released by filarial parasites likely contribute to the pathogenesis of filarial diseases. Adult heartworms ( Dirofilaria immitis) reside in the right heart and pulmonary artery, so the pulmonary artery should be exposed to the highest concentration of filarial factors. We tested the hypothesis that endothelium-dependent relaxation is altered in the in vitro pulmonary artery from heartworm-infected dogs. Relaxation responses to endothelium-dependent vasodilators (methacholine, bradykinin, substance P, and A-23187) and the non-endothelium-dependent vasodilator nitroglycerin and contractile responses were measured in rings of pulmonary artery from control and heartworm-infected dogs. Endothelium-dependent relaxation was assessed in the presence and absence of inhibitors of nitric oxide synthase, cyclooxygenase, and guanylate cyclase. Responses to methacholine, substance P, and A-23187, but not to bradykinin, nitroglycerin, norepinephrine, or KCl, were depressed in pulmonary artery from heartworm-infected dogs when compared with control, suggesting that changes in endothelial cell and not vascular smooth muscle behavior are involved in altered relaxation. The mechanism of endothelium-dependent relaxation in control pulmonary artery appears to involve nitric oxide in the case of methacholine and both nitric oxide and a cyclooxygenase product in the case of bradykinin and A-23187. The mechanism of endothelium-dependent relaxation in pulmonary artery from heartworm-infected dogs was not clearly elucidated. These data provide no evidence that heartworm infection globally influences either endothelial cell receptor function or the vascular smooth muscle guanylate cyclase guanosine 3′,5′-cyclic monophosphate system, making it likely that changes in intracellular signaling are primarily responsible for the observed alteration of endothelium-mediated relaxation. Alteration of endothelial cell function by filarial parasites may be an important component in the pathology associated with filariasis.

Two mechanisms mediate relaxation by bradykinin of pig coronary artery: NO-dependent and -independent responses

1991 ◽  
Vol 261 (3) ◽  
pp. H830-H835 ◽  
Author(s):  
C. L. Cowan ◽  
R. A. Cohen
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Coronary Artery ◽  
Thromboxane A2 ◽  
Porcine Coronary Artery ◽  
Cyclic Monophosphate ◽  
Pig Coronary Artery ◽  
Endothelium Dependent Relaxation

The role of nitric oxide and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the endothelium-dependent relaxation of the porcine coronary artery to bradykinin was investigated by comparing relaxation and cGMP accumulation in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) and methylene blue. Rings were treated with indomethacin to eliminate the effects of prostaglandins. Relaxation to bradykinin of rings contracted with the thromboxane A2 mimetic U-46619 was not affected by L-NMMA and was only minimally inhibited by methylene blue. Rings contracted with elevated potassium (25 mM) also relaxed completely to bradykinin. However, L-NMMA or methylene blue effectively inhibited relaxation to bradykinin in rings contracted with potassium. cGMP accumulation was stimulated by bradykinin and inhibited by L-NMMA or methylene blue in rings contracted with either U-46619 or potassium. These results suggest that in the absence of nitric oxide-induced cGMP accumulation, a nonprostanoid mechanism exists that is capable of completely relaxing U-46619-contracted coronary artery. This mechanism is either inhibited in or unable to relax potassium-contracted rings. These results also demonstrate that nitric oxide mediates the bradykinin-induced cGMP accumulation that is largely responsible for the relaxation during contraction with potassium.

Repeated endothelial removal augments intimal thickening and attenuates EDRF release

1994 ◽  
Vol 266 (4) ◽  
pp. H1348-H1356 ◽  
Author(s):  
Y. Niimi ◽  
H. Azuma ◽  
K. Hirakawa
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Carotid Arteries ◽  
Intimal Thickening ◽  
Endothelial Regeneration ◽  
Relaxing Factor ◽  
Endothelial Denudation ◽  
Endothelium Derived Relaxing Factor ◽  
Relaxation Responses ◽  
Progression Of Atherosclerosis

To evaluate the significance of repeated denudation injury in progression of atherosclerosis, we performed a single and then a second balloon denudation on the rabbit carotid arteries. Morphological examinations and organ chamber experiments were performed, and the results were compared. On morphological examinations, reendothelialization was almost completed in 2 wk after redenudation, whereas it required 6 wk after a single denudation. Intimal thickening progressed after redenudation. Organ chamber experiments showed that contractile responses and endothelium-independent relaxation remained unchanged after redenudation. Endothelium-dependent relaxations to acetylcholine, ADP, and substance P decreased progressively by repeating denudation. These relaxation responses were inhibited by NG-nitro-L-arginine, hemoglobin, and methylene blue and were considered to be associated with the production and/or release of endothelium-derived relaxing factor-nitric oxide (EDRF-NO). The diffusion barrier mechanism for the decreased endothelium-dependent relaxations was ruled out using sandwich experiments. In conclusion, repeated endothelial denudation caused progression of intimal thickening and acceleration of endothelial regeneration, and repeated endothelial regeneration resulted in progressively less production and/or release of EDRF-NO.

Endothelium-derived contracting and relaxing factors contribute to hypoxic responses of pulmonary arteries

1993 ◽  
Vol 265 (4) ◽  
pp. H1139-H1148 ◽  
Author(s):  
K. L. Kovitz ◽  
T. D. Aleskowitch ◽  
J. T. Sylvester ◽  
N. A. Flavahan
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arteries ◽  
Initial Response ◽  
Isometric Tension ◽  
No Synthase ◽  
Moderate Hypoxia ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Increased Activity ◽  
Endothelium Dependent Relaxation

The response of porcine pulmonary arteries to hypoxia depended on their location in the vasculature and the degree and duration of the hypoxic challenge. In rings of pulmonary artery suspended for isometric tension recording (37 degrees C, 16% O2 and 5% CO2), moderate hypoxia (10% and 4% O2) caused endothelium-dependent relaxation in distal arteries but transient endothelium-dependent contraction in proximal arteries. In both proximal and distal arteries, the initial response to anoxia (0% O2) was a transient endothelium-dependent contraction. This was followed by a slowly developing, sustained endothelium-dependent contraction in proximal arteries, or by an endothelium-independent relaxation in distal arteries. The endothelium-dependent relaxation to moderate hypoxia in distal arteries was inhibited only by combined inhibition of endothelium-derived relaxing factor (EDRF)-nitric oxide (NO) synthase [N omega-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (indomethacin), suggesting mediation by EDRF-NO and prostacyclin. Transient endothelium-dependent contractions to moderate hypoxia (proximal arteries) or anoxia (all arteries) were abolished by L-NAME, but the late endothelium-dependent anoxic contraction observed in proximal arteries was not reduced by L-NAME and/or indomethacin. Therefore, hypoxia/anoxia may initiate contraction of pulmonary arteries by decreasing the activity of EDRF-NO, but the contractions appear to be maintained by an increased activity of an endothelium-derived contracting factor.

Sign in / Sign up

Export Citation Format

Share Document