INTIMAL HYPERPLASIA IN HUMAN UTERINE ARTERIES ACCOMPANIED BY IMPAIREDSYNERGISM BETWEEN PROSTAGLANDIN I-2 AND NITRIC-OXIDE

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 uter ine arteries (UAs). 2 In order to assess the magnitude of intimal hype rplasia, the intima:media ratio (%) was estimated with the aid of an i mage analyser. Human UAs were classified into two groups, I and II on the basis of the ratio and the degree of elastin deposition of histolo gically normal specimens. The intima:media ratio in group II was deter mined 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 w as found in group I than in group II. 3 The relaxation activities of i loprost (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 syn ergistically in group I. The observed relaxation (48.7+/-8.8%, n=7) in this group was significantly (P<0.01) greater than the predicted valu e of 18.8+/-3.1% (n=7) (the mathematical sum of the relaxations caused by If and SNP alone). By contrast, these agents interacted in an addi tive manner in group II. The observed relaxation (20.8+/-9.5%, n=6) wa s 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 assay ed. When If and SNP at C-min were applied together to the UA strips, t hese compounds interacted synergistically in increasing cyclic nucleot ides in group I. The observed net increase in the content was determin ed to be 1.46+/-0.30 (P<0.05 vs. the predicted value of 0.67+/-0.12) i n this group (n=7). By contrast, the observed net increase (0.40+/-0.0 7, 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.