Role of endothelium-derived relaxing factor in active hyperemia of the canine diaphragm

1992 ◽  
Vol 72 (6) ◽  
pp. 2393-2401 ◽  
Author(s):  
S. N. Hussain ◽  
D. J. Stewart ◽  
J. P. Ludemann ◽  
S. Magder
Keyword(s):  
Vascular Resistance ◽  
Systemic Circulation ◽  
Mechanically Ventilated ◽  
Relaxing Factor ◽  
Arterial Blood ◽  
Left Diaphragm ◽  
Phrenic Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Dose Dependent

To assess the effect of endothelium-derived relaxing factor (EDRF) on diaphragmatic vascular resistance at rest and during contractions, we studied an in situ isolated diaphragm preparation in anesthetized and mechanically ventilated dogs. The arterial supply of the left diaphragm (phrenic artery) was catheterized and perfused with arterial blood at a fixed flow rate. Drugs were infused through a side port of the arterial catheter at 1/100th of the phrenic arterial flow. The inferior phrenic vein was catheterized to complete the isolation from the systemic circulation. Three sets of experiments were performed. In set 1 (n = 3), we infused endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) dilators at increasing concentrations. ACh and SNP infusion elicited a dose-dependent decline in phrenic vascular resistance (Rphr) at concentrations greater than 10(-8) M and 0.50 micrograms/ml, respectively. In set 2 (n = 15), we infused an inhibitor of EDRF synthesis and release, L-argininosuccinic acid (ArgSA), at increasing concentrations (10(-4), 3 x 10(-4), and 6 x 10(-4) M). ArgSA produced a dose-dependent increase in Rphr. Infusion of another EDRF inhibitor (NG-nitro-L-arginine, LNA, 6 x 10(-4) M) elicited increase in Rphr similar to that induced by ArgSA. In set 3 (n = 25), we infused ArgSA or LNA (6 x 10(-4) M) simultaneously with ACh and SNP and during sustained (2-Hz) contractions of the diaphragm. Both ArgSA and LNA completely reversed ACh vasodilation, whereas SNP vasodilation was reversed by 26 and 11%, respectively. ArgSA or LNA infusion during contractions reversed vasodilation by 48 and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of diaphragmatic oxygen uptake by endothelium-derived relaxing factor

1993 ◽  
Vol 265 (1) ◽  
pp. H123-H130 ◽  
Author(s):  
H. Y. Chang ◽  
M. E. Ward ◽  
S. N. Hussain
Keyword(s):  
Blood Flow ◽  
Saline Group ◽  
Mechanically Ventilated ◽  
O2 Extraction ◽  
Endogenous Nitric Oxide ◽  
Phrenic Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Stimulation Of

The role of endogenous nitric oxide (NO) in the regulation of phrenic blood flow (Qphr) and O2 consumption (VO2) of the in situ isolated left hemidiaphragms was assessed in two groups of anesthetized, mechanically ventilated dogs. Saline was infused into the phrenic artery for 20 min in one group, whereas N omega-nitro-L-arginine (L-NNA, 6 x 10(-4) M) was infused in the other (L-NNA) group. Qphr and diaphragmatic VO2 were measured at rest and during 2 min of continuous 3-Hz stimulation of the left phrenic nerve. The animals were progressively hemorrhaged, and the measurements were repeated at various arterial pressures (Pa). For the resting diaphragm, Qphr at a mean Pa of 145 mmHg was lower in the L-NNA group than in the saline group; however, diaphragmatic VO2 values were similar in both groups. Qphr decreased with the decline in Pa in both groups, but O2 extraction ratios obtained at mean Pa of 25–45 mmHg were similar in both groups (71 vs. 73%). For the contracting diaphragm, Qphr and diaphragmatic VO2 values at a given Pa were lower in the L-NNA group than in the saline group (except at mean Pa < 75 mmHg). O2 extraction ratios obtained at a given Pa were similar in both groups. We concluded that 1) EDRF inhibition limits diaphragmatic blood flow both at rest and during 3-Hz stimulation; 2) diaphragmatic O2 extraction is unaffected by EDRF inhibition; and 3) the effect of EDRF release on diaphragmatic VO2 is dependent on the level of metabolic demands.

Sodium hyperosmolarity of intestinal lymph causes arteriolar vasodilation in part mediated by EDRF

1993 ◽  
Vol 265 (1) ◽  
pp. H323-H328 ◽  
Author(s):  
J. M. Steenbergen ◽  
H. G. Bohlen
Keyword(s):  
Oleic Acid ◽  
Second Order ◽  
First Order ◽  
Acid Absorption ◽  
Intestinal Lymph ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Arteriolar Vasodilation ◽  
Dose Dependent

This study evaluated 1) the effect of increased submucosal lymph osmolarity on the regulation of first-order (1A) and second-order (2A) intestinal arterioles and 2) the role of endothelium-derived relaxing factor (EDRF) in hypertonic-induced vasodilation. Increasing the submucosal lymph osmolarity from 280 to 400 mosM, in increments of 30 mosM, resulted in a dose-dependent dilation of 1A and 2A. A submucosal lymph tonicity of 340 mosM, as occurs during glucose and oleic acid absorption, caused dilation of 1A (118%) and 2A (124%) equivalent to that during absorptive hyperemia. The dilation caused by 400 mosM mannitol (137%) was similar to that with 340 mosM NaCl (131%) and approximately 70% of that with 400 mosM NaCl (152%). After EDRF blockade, the responses to sodium hypertonicity decreased by about one-half; blockade reduced mannitol-induced dilation by 22%. These results indicate that sodium hypertonicity, as occurs during absorption, can play a major role in absorptive hyperemia, and about one-half of the dilation is related to a sodium-coupled release of EDRF.

scholarly journals N-hydroxylamine is not an intermediate in the conversion of l-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells

1991 ◽  
Vol 273 (3) ◽  
pp. 547-552 ◽  
Author(s):  
S Pou ◽  
W S Pou ◽  
G M Rosen ◽  
E E el-Fakahany
Keyword(s):  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Soluble Guanylate Cyclase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Intact Cells ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Dose Dependent

This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase.

Flow-induced release of EDRF in the pulmonary vasculature: site of release and action

1994 ◽  
Vol 267 (1) ◽  
pp. H363-H369 ◽  
Author(s):  
T. S. Hakim
Keyword(s):  
Vascular Resistance ◽  
Pulsatile Flow ◽  
Pressor Response ◽  
Autologous Blood ◽  
Pulmonary Vasculature ◽  
Small Arteries ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Pulsatile flow is thought to lower pulmonary vascular resistance by passive recruitment of capillaries and by active vasodilation. This study was undertaken to investigate the role of endothelium-derived relaxing factor (EDRF) during pulsatile flow in isolated canine left lower lobes pretreated with indomethacin. The lobes were perfused in situ with autologous blood (approximately 500 ml/min) using a nonpulsatile pump (Masterflex) or a pulsatile pump (Harvard). With the occlusion techniques, vascular resistance was partitioned into four segments: arterial (Ra), small arterial (R'a), small venous, and venous (Rv). Pulsatile flow (frequency = 70 min-1) did not lower total vascular resistance during baseline or during vasoconstriction. Distribution of vascular resistance among the four segments was not altered significantly by pulsatile flow during normoxia and angiotensin. In contrast, switching to pulsatile flow during hypoxia was associated with an increase in Ra and a decrease in R'a and Rv. N omega-nitro-L-arginine (L-NNA) had no effect on total or segmental resistance during baseline conditions but potentiated the hypoxic pressor response and prevented its recovery by 50%. In addition, the reduction in R'a by pulsatile flow was attenuated by L-NNA, suggesting that EDRF is released by pulsatile flow in this segment. We conclude that a shear stress-induced EDRF release from the small arteries is present in canine lungs and is experimentally demonstrable during pulsatile flow and hypoxia.

Modulation of cerebral arterial tone by endothelium-derived relaxing factor

1993 ◽  
Vol 264 (4) ◽  
pp. H1245-H1250 ◽  
Author(s):  
J. E. Brian ◽  
R. H. Kennedy
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Maximum Tension ◽  
Relaxing Factor ◽  
Middle Cerebral Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Vascular Smooth Muscle Tone ◽  
Dose Dependent ◽  
Arterial Tone

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

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)

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