Abstract
Purpose: This study explores at which level of the guanylate cyclase pathway oxygen modulates retinal pericyte relaxation induced by nitric oxide (NO). Methods: Bovine retinal microvascular pericytes were grown on silicone. On silicone, pericyte contractile tone induces wrinkles. Drug-induced relaxation was quantified as a reduced number of wrinkles after exposure to 3-morpholino-sydnonimine (SIN-I) or atrial natriuretic peptide (ANP) in the absence or in the presence of either 0.3 μM methylene blue (MB), a guanylate cyclase inhibitor, or 10 μM hemoglobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia). Results: Pericytes were relaxed with SIN-I and ANP in a concentration- dependent manner (EC 50:0.1 μM and 0.01 μM, respectively). Relaxations induced by SIN-I or ANP were inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN-I relaxations (P < 0.001). Relaxations induced by SIN-1, but not by ANP were increased (P < 0.001) under hypoxia and decreased (P=0.002) under hyperoxia. Conclusions: SIN-I and ANP relax pericytes through the activation of guanylate cyclase (inhibited by MB), but only SIN-I through an extracellular release of NO (inhibited by hemoglobin). That oxygen only modulates pericyte relaxations induced by SIN-I (NO-mediated) but not those induced by ANP suggests that an interaction between oxygen anti NO might participate in the capillary network's blood-flow modulation according to local tissue oxygen tension.
| Original language | English |
|---|---|
| Pages (from-to) | 1563-1568 |
| Number of pages | 6 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 38 |
| Issue number | 8 |
| State | Published - Aug 12 1997 |
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Keywords
- Eye
- Free radicals
- Glaucoma
- Optic nerve head circulation
- Retina
ASJC Scopus subject areas
- Ophthalmology
Cite this
Oxygen modulation of guanylate cyclase-mediated retinal pericyte relaxations with 3-morpholino-sydnonimine and atrial natriuretic peptide. / Haefligef, Ivan O.; Anderson, Douglas.
In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 8, 12.08.1997, p. 1563-1568.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxygen modulation of guanylate cyclase-mediated retinal pericyte relaxations with 3-morpholino-sydnonimine and atrial natriuretic peptide
AU - Haefligef, Ivan O.
AU - Anderson, Douglas
PY - 1997/8/12
Y1 - 1997/8/12
N2 - Purpose: This study explores at which level of the guanylate cyclase pathway oxygen modulates retinal pericyte relaxation induced by nitric oxide (NO). Methods: Bovine retinal microvascular pericytes were grown on silicone. On silicone, pericyte contractile tone induces wrinkles. Drug-induced relaxation was quantified as a reduced number of wrinkles after exposure to 3-morpholino-sydnonimine (SIN-I) or atrial natriuretic peptide (ANP) in the absence or in the presence of either 0.3 μM methylene blue (MB), a guanylate cyclase inhibitor, or 10 μM hemoglobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia). Results: Pericytes were relaxed with SIN-I and ANP in a concentration- dependent manner (EC 50:0.1 μM and 0.01 μM, respectively). Relaxations induced by SIN-I or ANP were inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN-I relaxations (P < 0.001). Relaxations induced by SIN-1, but not by ANP were increased (P < 0.001) under hypoxia and decreased (P=0.002) under hyperoxia. Conclusions: SIN-I and ANP relax pericytes through the activation of guanylate cyclase (inhibited by MB), but only SIN-I through an extracellular release of NO (inhibited by hemoglobin). That oxygen only modulates pericyte relaxations induced by SIN-I (NO-mediated) but not those induced by ANP suggests that an interaction between oxygen anti NO might participate in the capillary network's blood-flow modulation according to local tissue oxygen tension.
AB - Purpose: This study explores at which level of the guanylate cyclase pathway oxygen modulates retinal pericyte relaxation induced by nitric oxide (NO). Methods: Bovine retinal microvascular pericytes were grown on silicone. On silicone, pericyte contractile tone induces wrinkles. Drug-induced relaxation was quantified as a reduced number of wrinkles after exposure to 3-morpholino-sydnonimine (SIN-I) or atrial natriuretic peptide (ANP) in the absence or in the presence of either 0.3 μM methylene blue (MB), a guanylate cyclase inhibitor, or 10 μM hemoglobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia). Results: Pericytes were relaxed with SIN-I and ANP in a concentration- dependent manner (EC 50:0.1 μM and 0.01 μM, respectively). Relaxations induced by SIN-I or ANP were inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN-I relaxations (P < 0.001). Relaxations induced by SIN-1, but not by ANP were increased (P < 0.001) under hypoxia and decreased (P=0.002) under hyperoxia. Conclusions: SIN-I and ANP relax pericytes through the activation of guanylate cyclase (inhibited by MB), but only SIN-I through an extracellular release of NO (inhibited by hemoglobin). That oxygen only modulates pericyte relaxations induced by SIN-I (NO-mediated) but not those induced by ANP suggests that an interaction between oxygen anti NO might participate in the capillary network's blood-flow modulation according to local tissue oxygen tension.
KW - Eye
KW - Free radicals
KW - Glaucoma
KW - Optic nerve head circulation
KW - Retina
UR - http://www.scopus.com/inward/record.url?scp=0030807620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030807620&partnerID=8YFLogxK
M3 - Article
C2 - 9224284
AN - SCOPUS:0030807620
VL - 38
SP - 1563
EP - 1568
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 8
ER -