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TRANSLATIONAL PHYSIOLOGY

Endogenous estrogen attenuates pulmonary artery vasoreactivity and acute hypoxic pulmonary vasoconstriction: the effects of sex and menstrual cycle

Departments of ¹Surgery, ²Cellular and Integrative Physiology, ³Center for Immunobiology, and ⁴Division of Pulmonary, Allergy, Critical Care and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 5 March 2007 ; accepted in final form 3 June 2007

Sex differences exist in a variety of cardiovascular disorders. Sex hormones have been shown to mediate pulmonary artery (PA) vasodilation. However, the effects of fluctuations in physiological sex hormone levels due to sex and menstrual cycle on PA vasoreactivity have not been clearly established yet. We hypothesized that sex and menstrual cycle affect PA vasoconstriction under both normoxic and hypoxic conditions. Isometric force displacement was measured in isolated PA rings from proestrus females (PF), estrus and diestrus females (E/DF), and male (M) Sprague-Dawley rats. The vasoconstrictor response under normoxic conditions (organ bath bubbled with 95% O₂-5% CO₂) was measured after stimulation with 80 mmol/l KCl and 1 µmol/l phenylephrine. Hypoxia was generated by changing the gas to 95% N₂-5% CO₂. PA rings from PF demonstrated an attenuated vasoconstrictor response to KCl compared with rings from E/DF (75.58 ± 3.2% vs. 92.43 ± 4.24%, P < 0.01). Rings from M also exhibited attenuated KCl-induced vasoconstriction compared with E/DF (79.34 ± 3.2% vs. 92.43 ± 4.24%, P < 0.05). PA rings from PF exhibited an attenuated vasoconstrictor response to phenylephrine compared with E/DF (59.61 ± 2.98% vs. 70.03 ± 4.61%, P < 0.05). While the maximum PA vasodilation during hypoxia did not differ between PF, E/DF, and M, phase II of hypoxic pulmonary vasoconstriction was markedly diminished in the PA from PF (64.10 ± 7.10% vs. 83.91 ± 5.97% in M, P < 0.05). We conclude that sex and menstrual cycle affect PA vasoconstriction in isolated PA rings. Even physiological increases in circulating estrogen levels attenuate PA vasoconstriction under both normoxic and hypoxic conditions.

sex hormones; genomic and nongenomic effects; phenylephrine; potassium chloride

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