Pulmonary vascular reactivity is blunted in pregnant rats

Abstract

Pulmonary arterial pressure is decreased in pregnant women despite increased cardiac output, suggesting that pulmonary vascular resistance is decreased in pregnancy. To determine if pulmonary vascular reactivity is decreased in pregnant rats, lungs isolated from pregnant rats were perfused with blood from other pregnant rats at constant flow rate, and pressor responses to airway hypoxia and to angiotensin II were measured. Compared with responses obtained in lungs from nonpregnant female rats, hypoxic and angiotensin II pressor responses were blunted in pregnancy. To separate possible effects of pregnancy on the lung from those of substance(s) circulating in the blood in pregnancy, we perfused lungs from nonpregnant rats with blood from pregnant rats. Both the hypoxic and angiotensin II pressor responses were blunted by blood from pregnant rats. The angiotensin II pressor response was blunted also in lungs from pregnant rats perfused with blood from nonpregnant rats. These results suggest that a circulating substance is responsible for blunting of pulmonary vascular reactivity in pregnancy and that changes in the lung induced by pregnancy also depress angiotensin II responses. It is unlikely that estrogen and progesterone were responsible for these effects, since lungs and blood obtained from animals treated with these hormones did not have blunted pulmonary vascular reactivity.

Evidence against the hypothesis that prostaglandins are the vasodepressor agents of pregnancy. Serial studies in chronically instrumented, conscious rats.

“…This finding is consonant with studies ofpulmonary vascular reactivity in pregnant rats (67) and dogs (68), in which the response to hypoxia and to infusions of All or PGF2. was depressed.…”

The estrogen paradox in pulmonary arterial hypertension

“…IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION (PAH) is a disabling condition characterized by PA vasoconstriction and remodeling as well as in situ thrombosis and eventually right heart failure (9,30,40). Idiopathic PAH occurs more frequently in females than in males.…”

Evidence for attenuation of myo-inositol uptake, phosphoinositide turnover and inositol phosphate production in aortic vasculature of rats during pregnancy.

“…Thus, the pregnant rat may be a useful animal model in which to investigate mechanism(s) responsible for maternal vasodilation and attenuated vascular reactivity to vasoconstrictor hormones. Since blood vessels of gravid rats (14)(15)(16)(17)(18)(19)(20), rabbits (21), cats (21), and guinea pigs (22) demonstrate decreased vascular reactivity in vitro or in situ, it seems likely that alterations within the vasculature itself are important. Vasoconstrictor receptor desensitization during pregnancy does not appear to account for the refactory vascular response, at least to angiotensin II and arginine vasopressin (23)(24)(25)(26).…”

“…The following day, after removal of a residual aqueous layer, the organic phase was dried (Savant Speedvac Concentrator, Savant Instruments, Inc., Farmingdale, NY or N-Evap; Organomation, South Berlin, MA). Unlabeled phospholipid standards were added to the residue: 25 MAg phosphatidylinositol-4,5-bisphosphate, 15 Mg lysophosphatidylinositol, 10 Mg phosphatidylinositol4-phosphate, and 10 MAg phosphatidylinositol (Sigma Chemical Co., St. Louis, MO). The sides of the vials were washed with an additional 0.5 ml of the acidified extraction mixture, and after drying, the residue was resuspended in 100 MI CHC13:CH3OH:H20-37.5:12.5:1, and sonicated for 5 min (Branson Co., Shelton, CT).…”

“…Aortic segments were preincubated for Plasma concentration ofmyoinositol, enzymatic-fluorometric assay (adapted and modifiedfrom references 36 and 37). 500 MA ofplasma was chilled on ice and treated with 500 MI of ice-cold 0.6 N HC104 for 15 min. The mixture was vortexed every 5 min and the precipitated proteins were pelleted by centrifugation.…”