TY - JOUR
T1 - Nitric oxide (NO) donor molecules
T2 - Effect of NO release rate on vascular smooth muscle cell proliferation in vitro
AU - Mooradian, Daniel L.
AU - Hutsell, Thomas C.
AU - Keefer, Larry K.
PY - 1995/4
Y1 - 1995/4
N2 - Nitric oxide (NO) inhibits vascular smooth muscle cell (SMC) growth in vitro. To determine the effects of release rate and exposure time on SMC growth inhibition by NO, we compared the activities of five NO donors that generate NO with half-lives of 2 min (DEA/NO, Et2N[N202]Na), 15 min (PAPA/NO, CH3(CH2)2N[N202]-(CH2)3NH3+), 39 min, (SPER/NO, H2N(CH2)3NH2+(CH2)4N[N202]-(CH2)3NH2), 3 h (DPTA/NO, H2N(CH2)4N[N202] (CH2)3NH3+), and 20 h(DETA/NO, H2N(CH2)2N[N202]-(CH2)2NH3+). After 22-h treatment, rat aorta SMC (RA-SMC) DNA synthesis was inhibited with IC50values of 180, 60, and 40 μM for SPER/NO, DPTA/NO, and DETA/NO, respectively. DEA/NO and PAPA/NO did not inhibit DNA synthesis significantly at any concentration tested (20-500 μM). The inhibitory effect of NO on RA-SMC DNA synthesis was thus greatest when a given molar dose of NO was delivered slowly throughout the 22-h period. The antiproliferative effect of DETA/NO was confirmed by measurement of cell numbers for 7 days. When RA-SMC were treated with 500 μM DETA/NO on days 1, 3, and 5, growth was completely suppressed. Cell viability was > 95%, confirming that DETA/NO was not cytotoxic. The results suggest that NO donors may be useful inhibitors of intimal hyperplasia and restenosis after vascular injury such as balloon angioplasty.
AB - Nitric oxide (NO) inhibits vascular smooth muscle cell (SMC) growth in vitro. To determine the effects of release rate and exposure time on SMC growth inhibition by NO, we compared the activities of five NO donors that generate NO with half-lives of 2 min (DEA/NO, Et2N[N202]Na), 15 min (PAPA/NO, CH3(CH2)2N[N202]-(CH2)3NH3+), 39 min, (SPER/NO, H2N(CH2)3NH2+(CH2)4N[N202]-(CH2)3NH2), 3 h (DPTA/NO, H2N(CH2)4N[N202] (CH2)3NH3+), and 20 h(DETA/NO, H2N(CH2)2N[N202]-(CH2)2NH3+). After 22-h treatment, rat aorta SMC (RA-SMC) DNA synthesis was inhibited with IC50values of 180, 60, and 40 μM for SPER/NO, DPTA/NO, and DETA/NO, respectively. DEA/NO and PAPA/NO did not inhibit DNA synthesis significantly at any concentration tested (20-500 μM). The inhibitory effect of NO on RA-SMC DNA synthesis was thus greatest when a given molar dose of NO was delivered slowly throughout the 22-h period. The antiproliferative effect of DETA/NO was confirmed by measurement of cell numbers for 7 days. When RA-SMC were treated with 500 μM DETA/NO on days 1, 3, and 5, growth was completely suppressed. Cell viability was > 95%, confirming that DETA/NO was not cytotoxic. The results suggest that NO donors may be useful inhibitors of intimal hyperplasia and restenosis after vascular injury such as balloon angioplasty.
KW - Angioplasty
KW - Hyperplasia
KW - Nitric oxide
KW - Proliferation
KW - Restenosis
KW - Vascular smooth muscle
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U2 - 10.1097/00005344-199504000-00023
DO - 10.1097/00005344-199504000-00023
M3 - Article
C2 - 7596138
AN - SCOPUS:0028925540
SN - 0160-2446
VL - 25
SP - 674
EP - 678
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 4
ER -