EFFECT OF PREGNANCY ON VASCULAR CGMP PRODUCTION AND VASORELAXATION INTHE RAT

Objective: To determine whether vascular endothelium-derived relaxing factor (EDRF) activity is enhanced during gestation in the rat. Method s: Because cyclic guanosine 3',5'-monophosphate (cGMP) is a second mes senger which mediates vascular smooth muscle relaxation by EDRF, we me asured basal and stimulated cCMP levels in isolated aortas from virgin and pregnant rats. Endothelium-dependent and -independent relaxation responses were also assessed in isolated aortas. Finally, endothelium- dependent and -independent hypotensive responses were tested in chroni cally instrumented, conscious virgin, and gravid rats. Results: (1) Ba sal levels of aortic cGMP were not significantly different between vir gin and-gravid rats; whether the vessels were incubated in the presenc e or absence of 0.1 mM 3-isobutyl-1-methyl-xanthine and 1.0 mM L-argin ine. Further, reduced hemoglobin or endothelial removal decreased cGMP to the same level in the aortas from the two groups of rats. (2) Meth acholine-stimulated production of cGMP was greater in aortas obtained from gravid rats than from virgin controls (P < 0.001), albeit at dosa ges which exceeded those required to produce half-maximal or even maxi mal in vitro relaxation. (3) Stimulated production of cGMP by histamin e was less in the vessels from pregnant rats (P < 0.004), while that p roduced by ADP, bradykinin, mellitin, A23187, and sodium nitroprusside was not significantly different between the two groups of animals. (4 ) The relaxation responses of isolated aortic rings from gravid and vi rgin rats to both methacholine and sodium nitroprusside were comparabl e. (5) The peak hypotensive responses to methacholine, sodium nitropru sside, and isoproterenol were also similar between conscious pregnant and virgin rats. Conclusions: (1) Basal levels of cGMP in aortae isola ted from virgin and pregnant rats are not significantly different, sug gesting that basal production of nitric oxide by endothelial cell cons titutive nitric oxide synthase is comparable, and that the inducible n itric oxide synthase is not expressed by this vessel during rat gestat ion. (2) The postreceptor pathways for EDRF and cGMP synthesis are com parable in aortas obtained from pregnant and virgin rats, and the diff erences in cGMP production by methacholine and histamine in these vess els from the two groups of rats may be due to gestational alterations of receptor function. (3) The physiological meaning of increased cGMP production observed in aortas of pregnant rats in response to methacho line is uncertain, because the in vitro relaxation and in vivo hypoten sive responses to the agent were not significantly altered by gestatio n.