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Intimal hyperplasia in human uterine arteries accompanied by impaired synergism between prostaglandin I 2 and nitric oxide
Author(s) -
Obayashi Satoshi,
Aso Takeshi,
Sato Jun,
Hamasaki Hidehisa,
Azuma Hiroshi
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15779.x
Subject(s) - nitric oxide , prostaglandin , medicine , endocrinology , intimal hyperplasia , chemistry , smooth muscle
1 The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I 2 (PGI 2 ) and nitric oxide (NO) in human uterine arteries (UAs). 2 In order to assess the magnitude of intimal hyperplasia, the intimaimedia ratio (%) was estimated with the aid of an image analyser. Human UAs were classified into two groups, I and II on the basis of the ratio and the degree of elastin deposition of histologically normal specimens. The intimaimedia ratio in group II was determined to be 38.9 ± 7.7% ( n = 6), which was significantly ( P < 0.01) higher than that in group I (16.5 ± 1.5%, n = 7). Less deposition of elastin was found in group I than in group II. 3 The relaxation activities of iloprost (IP) as a stable analogue of PGI 2 and sodium nitroprusside (SNP) as a NO donor were not different between the two groups. When the minimum concentrations (C min ) of IP and SNP in producing relaxation were applied together to the UA strips, these compounds interacted synergistically in group I. The observed relaxation (48.7 ± 8.8%, n = 7) in this group was significantly ( P < 0.01) greater than the predicted value of 18.8 ± 3.1% ( n = 7) (the mathematical sum of the relaxations caused by IP and SNP alone). By contrast, these agents interacted in an additive manner in group II. The observed relaxation (20.8 ± 9.5%, n = 6) was not significantly different from the predicted value (18.6 ± 2.4%, n = 6) in this group. 4 During the relaxation produced by the addition of IP and SNP alone or in combination, the changes in cyclic nucleotides (cyclic AMP and cyclic GMP) contents (pmol mg −1 protein) were assayed. When IP and SNP at C min were applied together to the UA strips, these compounds interacted synergistically in increasing cyclic nucleotides in group I. The observed net increase in the content was determined to be 1.46 ± 0.30 ( P < 0.05 vs . the predicted value of 0.67 ± 0.12) in this group ( n = 7). By contrast, the observed net increase (0.40 ± 0.07, n = 6) did not exceed the predicted value (0.65 ± 0.07, n = 6) in group II. 5 These results suggest that the formation of intimal hyperplasia in group II may be closely related to the impaired synergism between PGI 2 and NO in the human UAs.