Endothelium-dependent and independent cGMP mechanisms appear to mediate O2 responses in calf pulmonary resistance arteries

1992 ◽  
Vol 262 (5) ◽  
pp. L560-L565 ◽  
Author(s):  
H. A. Omar ◽  
M. S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Resistance Arteries ◽  
Pulmonary Resistance ◽  
Cyclic Monophosphate ◽  
Relaxing Factor ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation

Our laboratory has previously described in isolated 1- to 4-mm calf pulmonary arteries, an endothelium-independent contraction to hypoxia that appears to involve the removal of a H2O2-elicited guanosine 3',5'-cyclic monophosphate (cGMP)-mediated relaxation. In this study, we examined the effects of changes in O2 tension (PO2) on isolated endothelium-intact and endothelium-denuded calf pulmonary resistance arteries of approximately 200 microns in diameter. Resistance arteries precontracted with U46619 were found to undergo a contraction when exposed to a PO2 of 24–27 Torr (hypoxia) from a Po2 of 150 Torr (O2 atmosphere). This contraction was significantly larger in endothelium-intact than endothelium-removed arteries. In the intact artery, 30 microM nitro-L-arginine (NLA), an inhibitor of the biosynthesis of nitric oxide-like activators of guanylate cyclase, increased tone under O2 atmosphere and reduced the contraction to hypoxia to the level observed in the endothelium-removed artery. Reoxygenation caused a relaxation, which was not dependent on the endothelium or inhibited by NLA. The inhibitor of guanylate cyclase activation, LY83583 (10 microM), increased tone under O2 atmosphere, eliminated the contraction to hypoxia, and inhibited the relaxation to reoxygenation, whereas indomethacin (10 microM) did not alter these responses. Thus modulation of a cGMP mechanism, not involving the endothelium or metabolism of arginine, is a primary mediator of responses to changes in O2 tension, and the endothelium appears to cause an enhancement of the contraction to hypoxia via suppression by hypoxia of the tonic generation of an arginine-derived relaxing factor.

NO and H2O2 mechanisms of guanylate cyclase activation in oxygen-dependent responses of rat pulmonary circulation

1995 ◽  
Vol 268 (4) ◽  
pp. L546-L550 ◽  
Author(s):  
J. A. Monaco ◽  
T. Burke-Wolin
Keyword(s):  
Oxygen Tension ◽  
Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Similar Degree ◽  
Rat Lung ◽  
Regulatory Pathways ◽  
Cyclase Activation ◽  
No Formation ◽  
Hypoxic Vasoconstriction ◽  
Guanylate Cyclase Activation

Pulmonary hypoxic vasoconstriction appears to have both endothelium-dependent and -independent regulatory pathways. We have previously described a mechanism of guanylate cyclase activation in isolated pulmonary arteries that is smooth muscle contained and oxygen tension dependent. In this study we examine this mechanism, involving H2O2 metabolism by catalase, and its relationship to endothelial-derived nitric oxide in the regulation of pulmonary artery pressure (PAP) by oxygen tension. Using probes selective for these two distinct mechanisms of guanylate cyclase activation, we found in the isolated buffer-perfused rat lung that 100 microM nitro-L-arginine (NLA), an inhibitor of NO formation, increased baseline PAP from 4.8 +/- 0.6 to 6.0 +/- 0.6 mmHg and hypoxic PAP from 6.8 +/- 0.8 to 8.56 +/- 0.6 mmHg. Aminotriazole (AT), an inhibitor of H2O2 metabolism by catalase, also increased PAP from 4.5 +/- 0.9 to 6.1 +/- 2.0 mmHg (P < or = 0.05) and hypoxic PAP from 6.0 +/- 1.7 to 8.7 +/- 2.7 mmHg (P < or = 0.05). Additionally, while NLA did not affect the vasodilation that occurs upon reoxygenation, AT inhibited the immediate response to reoxygenation. In the presence of both NLA and AT, baseline PAP increased from 4.25 +/- 0.8 to 9.9 +/- 0.92 mmHg (P < or = 0.05), but hypoxia did not significantly increase PAP and the reoxygenation response was inhibited. These data suggest that both NO and H2O2-catalase mechanisms contribute to a similar degree to maintain low PAP under normoxic conditions. The removal of either mediator may contribute to hypoxic vasoconstriction.

Nitric oxide-induced microvascular permeability alterations: a regulatory role for cGMP

1993 ◽  
Vol 265 (6) ◽  
pp. H1909-H1915 ◽  
Author(s):  
P. Kubes
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Guanylate Cyclase ◽  
Microvascular Permeability ◽  
Independent Effect ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Protein Clearance ◽  
Guanylate Cyclase Activation ◽  
Permeability Alterations

This study evaluated the physiological effects of compounds that alter guanosine 3',5'-cyclic monophosphate (cGMP) on the increase in vascular protein clearance induced by nitric oxide (NO) synthesis inhibition in the feline small intestine. A lymphatic vessel draining the small bowel was cannulated; vascular protein clearance and intestinal blood flow were measured. N omega-nitro-L-arginine methyl ester (L-NAME), the NO inhibitor, was infused (0.5 mumol/min) into the superior mesenteric artery. Vascular protein clearance increased approximately 4.6-fold, whereas blood flow decreased to 50% of control. Elevation of cGMP by 1) cytosolic guanylate cyclase activation with a NO donor (SIN 1) or 2) a cGMP analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) completely prevented the rise in microvascular permeability associated with L-NAME. Moreover, these compounds reduced (almost 90%) baseline vascular protein clearance, whereas inhibition of cytosolic guanylate cyclase with methylene blue significantly increased this parameter. Atrial natriuretic factor (ANF) has been reported to increase tissue cGMP levels and microvascular permeability. In this study, ANF did indeed increase intestinal microvascular permeability however this occurred independent of changes in intestinal cGMP levels. These data support a role for cGMP associated with NO-induced microvascular permeability alterations and raise the possibility that ANF has a cGMP-independent effect on microvascular permeability within the intestine.

Role of nitric oxide and phosphodiesterase isoenzyme II for reduction of endothelial hyperpermeability

1996 ◽  
Vol 270 (3) ◽  
pp. C778-C785 ◽  
Author(s):  
N. Suttorp ◽  
S. Hippenstiel ◽  
M. Fuhrmann ◽  
M. Krull ◽  
T. Podzuweit
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Guanylate Cyclase ◽  
Endothelial Permeability ◽  
No Donors ◽  
Cyclase Activation ◽  
Pde Inhibition ◽  
Synthase Inhibitor ◽  
Guanylate Cyclase Activation ◽  
Endothelial Hyperpermeability

Regulation of endothelial permeability is poorly understood. Previous studies have shown that endothelial cells contain phosphodiesterase (PDE) isoenzymes II-IV and that simultaneous adenylate cyclase activation and/or PDE inhibition blocked endothelial hyperpermeability (J.Clin.Invest. 91: 1421-1428, 1993). We now focused on a possible role for guanosine 3',5'-cyclic monophosphate (cGMP)-dependent mechanisms and studied H2O2-exposed porcine pulmonary artery endothelial cell monolayers. Pretreatment of cells with different nitric oxide (NO) donors or atrial natriuretic peptide (ANP) increased endothelial cGMP-content severalfold and blocked H2O2-related effects on permeability; opposite results were obtained with a NO synthase inhibitor. Determination of cGMP degradation in nitroprusside-exposed endothelial cells identified PDE II as the major cGMP metabolizing pathway, whereas PDE III and IV contributed little or nothing. Inhibition of PDE II reduced H2O2-related endothelial hyperpermeability, an effect that could be enhanced synergistically by simultaneous guanylate cyclase activation. In summary, these studies indicate that cGMP-dependent mechanisms (NO donors, ANP, and dibutyryl-cGMP) blocked H2O2-related increases in endothelial permeability. The major cGMP degrading pathway in endothelial cells was PDE II, thereby substituting the missing PDE V in these cells. Simultaneous guanylate cyclase activation and/or PDE II inhibition may be a valuable approach to treat endothelial hyperpermeability.

Inhibition of cGMP-associated pulmonary arterial relaxation to H2O2 and O2 by ethanol

1990 ◽  
Vol 258 (5) ◽  
pp. H1267-H1273 ◽  
Author(s):  
T. M. Burke-Wolin ◽  
M. S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Guanylate Cyclase ◽  
Muscle Tone ◽  
Pulmonary Arteries ◽  
Arterial Relaxation ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Guanylate Cyclase Activation

We have recently suggested that relaxation of isolated precontracted intrapulmonary arteries from calves to H2O2 or O2 may involve the activation of guanylate cyclase by peroxide metabolism via catalase. In this study, ethanol, an agent that modulates peroxide metabolism by catalase and selectively inhibits the activation of guanylate cyclase by H2O2 but not by nitric oxide-related activators, was employed to further investigate the role of catalase in pulmonary arterial relaxation and guanylate cyclase activation by O2 and H2O2. In precontracted pulmonary arteries, ethanol reverses H2O2-elicited relaxation and increases in guanosine 3',5'-cyclic monophosphate (cGMP) tissue levels without affecting similar responses to nitroprusside. The pulmonary arteries employed in this study show a hypoxic contraction that is associated with decreases in cGMP levels, and reoxygenation produces a somewhat phasic relaxation and a marked increase in cGMP levels. Ethanol produces an O2 tension-dependent contraction and reverses relaxation to reoxygenation associated with inhibition of O2-elicited increases in cGMP levels. Thus ethanol appears to function as a mimic of hypoxia by inhibiting relaxations elicited by O2. These findings support a hypothesized role for H2O2-dependent activation of guanylate cyclase in O2-dependent regulation of pulmonary arterial smooth muscle tone.

NO elicits prolonged relaxation of bovine pulmonary arteries via endogenous peroxynitrite generation

1997 ◽  
Vol 273 (2) ◽  
pp. L437-L444 ◽  
Author(s):  
C. A. Davidson ◽  
P. M. Kaminski ◽  
M. S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Guanylate Cyclase ◽  
Superoxide Anion ◽  
Pulmonary Arteries ◽  
Force Generation ◽  
Acute Exposure ◽  
Diethyl Maleate ◽  
Cyclic Monophosphate

We previously reported that acute exposure of endothelium-removed bovine pulmonary arteries (BPA) to high levels (0.1 mM) of peroxynitrite (ONOO-) caused a prolonged guanosine 3',5'-cyclic monophosphate-related relaxation that appeared to be mediated through a thiol-dependent generation of nitric oxide (NO). In this study, we examined the importance of endogenous ONOO- formation in the regulation of BPA force generation by elevated physiological levels of NO. Exposure of BPA precontracted with 30 mM KCl to approximately 50 nM NO for 2 min caused a subsequent prolonged relaxation of KCl-induced force and an increased release of NO (measured in head space gas after a 5-min deoxygenation with 95% N2-5% CO2). This subsequent release of NO was reduced after depletion of tissue glutathione with diethyl maleate (DEM). Also, the NO-elicited prolonged relaxation of BPA was reversed by post-NO treatment with 10 microM methylene blue (MB; which inhibits guanylate cyclase stimulation by NO) or 1 microM oxyhemoglobin (which traps NO). Furthermore, inhibiting the biosynthesis of endogenous superoxide anion (O2-.) with 1 microM diphenyliodonium (DPI) or scavenging O2-. with 10 mM Tiron also promoted reversal of the NO-elicited prolonged relaxation seen in BPA after NO gas exposure. During exposure of BPA smooth muscle to approximately 50 nM NO gas, there appears to be a marked increase in ONOO- formation as detected by a DPI- and Tiron-inhibitable prominent increase in luminol-dependent chemiluminescence and a decrease in O2-. levels as detected by a reduction in lucigenin-dependent chemiluminescence during exposure to NO. Thus, during exposure to elevated physiological levels of NO, BPA appear to produce ONOO-, a species that seems to participate in prolonging the initial relaxation to NO through a thiol-dependent trapping and/or regeneration of NO.

Nitric Oxide (NO)–Dependent but Not NO-Independent Guanylate Cyclase Activation Attenuates Hypoxic Vasoconstriction in Rabbit Lungs

2000 ◽  
Vol 23 (2) ◽  
pp. 222-227 ◽  
Author(s):  
Norbert Weissmann ◽  
Robert Voswinckel ◽  
André Tadić ◽  
Thorsten Hardebusch ◽  
Hossein Ardeschir Ghofrani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Cyclase Activation ◽  
Hypoxic Vasoconstriction ◽  
Guanylate Cyclase Activation

Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite

1981 ◽  
Vol 59 (2) ◽  
pp. 150-156 ◽  
Author(s):  
Carl A. Gruetter ◽  
Philip J. Kadowitz ◽  
Louis J. Ignarro
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Guanylate Cyclase ◽  
Sodium Nitrite ◽  
Soluble Guanylate Cyclase ◽  
Enzyme Activation ◽  
Amyl Nitrite ◽  
Cyclase Activation ◽  
Guanylate Cyclase Activation

Relaxation by nitroglycerin, sodium nitrite, and amyl nitrite of bovine coronary arterial smooth muscle was inhibited by the oxidant methylene blue. Methylene blue also inhibited activation of bovine coronary arterial soluble guanylate cyclase by nitroglycerin, which required addition of cysteine. At concentrations less than 10 mM, sodium nitrite required the addition of one of several thiols or ascorbate to activate guanylate cyclase from bovine coronary artery. Guanylate cyclase activation by large amounts (50 μL) of saturated amyl nitrite gas did not require, but was enhanced by, the addition of thiols or ascorbate. However, similar to sodium nitrite, guanylate cyclase activation by smaller amounts (5 μL) of saturated amyl nitrite gas did require the addition of one of various thiols or ascorbate. Methylene blue markedly inhibited guanylate cyclase activation by sodium nitrite in the presence of cysteine or ascorbate and similarly inhibited enzyme activation by amyl nitrite either in the absence or presence of cysteine or ascorbate. These data support the hypothesis that nitrates and nitrites relax vascular smooth muscle by stimulating cyclic GMP formation. The results further suggest that, similar to relaxation and guanylate cyclase activation by nitroso-containing compounds, relaxation and enzyme activation by nitrates and nitrites may involve the formation of nitric oxide or complexes of nitric oxide as active intermediates.

Sign in / Sign up

Export Citation Format

Share Document