Relaxation of retinal pericyte contractile tone through the nitric oxide- cyclic guanosine monophosphate pathway

F. O. Haefliger, A. Zschauer, Douglas Anderson

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Purpose. Pericytes are contractile cells outside the endothelial lining of capillaries. The study investigated whether nitric oxide, known to cause relaxation of vascular smooth muscle cells, also relaxes pericytes. Methods. Cultured bovine pericytes were exposed to a nitric oxide donor, sodium nitroprusside, and to 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo cGMP) in the presence and in the absence of methylene blue, an inhibitor of guanylate cyclase. Relaxation was assessed by counting the loss of wrinkles induced by pericytes when they are cultured on thin sheets of silicone. Intracellular cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay. Results. Pericytes relaxed to sodium nitroprusside (3 x 10-8 to 10-4 M) in a concentration-dependent manner (ED50: 10-6 M). The maximal response was characterized by the loss of almost all the wrinkles. The half-maximal relaxation was strongly inhibited by methylene blue (3 x 10-7 M). Sodium nitroprusside (3 x 10-6 M) caused a 14-fold increase in the intracellular concentration of cGMP, an effect inhibited by methylene blue (3 x 10-7 M). The cGMP analogue, 8-bromo-cGMP (10-5 and 3 x 10-5 M) strongly relaxed the cells in a concentration-dependent manner, but the relaxation was not reduced by methylene blue (3 x 10-7 M). Conclusions. Sodium nitroprusside, which releases nitric oxide, strongly relaxes pericytes through an increase of cGMP. Therefore, the presence of the endothelium-derived relaxing factor nitric oxide in the microcirculation can modulate the tone of pericytes, and it thus has the potential to influence blood flow in capillaries.

Original languageEnglish
Pages (from-to)991-997
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume35
Issue number3
StatePublished - Jan 1 1994

Fingerprint

Pericytes
Cyclic GMP
Nitric Oxide
Methylene Blue
Nitroprusside
Guanosine Monophosphate
Endothelium-Dependent Relaxing Factors
Nitric Oxide Donors
Guanylate Cyclase
Silicones
Microcirculation
Vascular Smooth Muscle
Smooth Muscle Myocytes
Radioimmunoassay
Endothelial Cells

Keywords

  • 3':5'- cyclic monophosphate
  • 8-bromoguanosine
  • guanylate cyclase
  • methylene blue
  • pericytes
  • sodium nitroprusside

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Relaxation of retinal pericyte contractile tone through the nitric oxide- cyclic guanosine monophosphate pathway. / Haefliger, F. O.; Zschauer, A.; Anderson, Douglas.

In: Investigative Ophthalmology and Visual Science, Vol. 35, No. 3, 01.01.1994, p. 991-997.

Research output: Contribution to journalArticle

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abstract = "Purpose. Pericytes are contractile cells outside the endothelial lining of capillaries. The study investigated whether nitric oxide, known to cause relaxation of vascular smooth muscle cells, also relaxes pericytes. Methods. Cultured bovine pericytes were exposed to a nitric oxide donor, sodium nitroprusside, and to 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo cGMP) in the presence and in the absence of methylene blue, an inhibitor of guanylate cyclase. Relaxation was assessed by counting the loss of wrinkles induced by pericytes when they are cultured on thin sheets of silicone. Intracellular cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay. Results. Pericytes relaxed to sodium nitroprusside (3 x 10-8 to 10-4 M) in a concentration-dependent manner (ED50: 10-6 M). The maximal response was characterized by the loss of almost all the wrinkles. The half-maximal relaxation was strongly inhibited by methylene blue (3 x 10-7 M). Sodium nitroprusside (3 x 10-6 M) caused a 14-fold increase in the intracellular concentration of cGMP, an effect inhibited by methylene blue (3 x 10-7 M). The cGMP analogue, 8-bromo-cGMP (10-5 and 3 x 10-5 M) strongly relaxed the cells in a concentration-dependent manner, but the relaxation was not reduced by methylene blue (3 x 10-7 M). Conclusions. Sodium nitroprusside, which releases nitric oxide, strongly relaxes pericytes through an increase of cGMP. Therefore, the presence of the endothelium-derived relaxing factor nitric oxide in the microcirculation can modulate the tone of pericytes, and it thus has the potential to influence blood flow in capillaries.",
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N2 - Purpose. Pericytes are contractile cells outside the endothelial lining of capillaries. The study investigated whether nitric oxide, known to cause relaxation of vascular smooth muscle cells, also relaxes pericytes. Methods. Cultured bovine pericytes were exposed to a nitric oxide donor, sodium nitroprusside, and to 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo cGMP) in the presence and in the absence of methylene blue, an inhibitor of guanylate cyclase. Relaxation was assessed by counting the loss of wrinkles induced by pericytes when they are cultured on thin sheets of silicone. Intracellular cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay. Results. Pericytes relaxed to sodium nitroprusside (3 x 10-8 to 10-4 M) in a concentration-dependent manner (ED50: 10-6 M). The maximal response was characterized by the loss of almost all the wrinkles. The half-maximal relaxation was strongly inhibited by methylene blue (3 x 10-7 M). Sodium nitroprusside (3 x 10-6 M) caused a 14-fold increase in the intracellular concentration of cGMP, an effect inhibited by methylene blue (3 x 10-7 M). The cGMP analogue, 8-bromo-cGMP (10-5 and 3 x 10-5 M) strongly relaxed the cells in a concentration-dependent manner, but the relaxation was not reduced by methylene blue (3 x 10-7 M). Conclusions. Sodium nitroprusside, which releases nitric oxide, strongly relaxes pericytes through an increase of cGMP. Therefore, the presence of the endothelium-derived relaxing factor nitric oxide in the microcirculation can modulate the tone of pericytes, and it thus has the potential to influence blood flow in capillaries.

AB - Purpose. Pericytes are contractile cells outside the endothelial lining of capillaries. The study investigated whether nitric oxide, known to cause relaxation of vascular smooth muscle cells, also relaxes pericytes. Methods. Cultured bovine pericytes were exposed to a nitric oxide donor, sodium nitroprusside, and to 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo cGMP) in the presence and in the absence of methylene blue, an inhibitor of guanylate cyclase. Relaxation was assessed by counting the loss of wrinkles induced by pericytes when they are cultured on thin sheets of silicone. Intracellular cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay. Results. Pericytes relaxed to sodium nitroprusside (3 x 10-8 to 10-4 M) in a concentration-dependent manner (ED50: 10-6 M). The maximal response was characterized by the loss of almost all the wrinkles. The half-maximal relaxation was strongly inhibited by methylene blue (3 x 10-7 M). Sodium nitroprusside (3 x 10-6 M) caused a 14-fold increase in the intracellular concentration of cGMP, an effect inhibited by methylene blue (3 x 10-7 M). The cGMP analogue, 8-bromo-cGMP (10-5 and 3 x 10-5 M) strongly relaxed the cells in a concentration-dependent manner, but the relaxation was not reduced by methylene blue (3 x 10-7 M). Conclusions. Sodium nitroprusside, which releases nitric oxide, strongly relaxes pericytes through an increase of cGMP. Therefore, the presence of the endothelium-derived relaxing factor nitric oxide in the microcirculation can modulate the tone of pericytes, and it thus has the potential to influence blood flow in capillaries.

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