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Sex differences in pulmonary vascular control: focus on the nitric oxide pathway
Daphne P M de Wijs-Meijler1,2, A H Jan Danser3, Irwin K M Reiss2
1Division of Experimental Cardiology, Department of Cardiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands d.merkus@erasmusmc.nl.
Physiological Reports
|June 10, 2017
Summary
Male and female swine show distinct pulmonary vascular responses to nitric oxide and PDE5 inhibition, suggesting sex differences in pulmonary vascular tone regulation. This finding may explain variations in pulmonary hypertension.
Area of Science:
- Cardiovascular Physiology
- Pulmonary Vascular Disease
- Sex Differences in Medicine
Background:
- Pulmonary hypertension (PH) affects females more in incidence, but males exhibit worse severity and prognosis.
- Existing research on sex differences in PH primarily explores sex hormones, neglecting vascular signaling pathways.
- Understanding sex-specific regulation of pulmonary vascular function is crucial for improving PH treatment and outcomes.
Purpose of the Study:
- To investigate sex differences in pulmonary vascular function in male and female swine.
- To examine the role of the nitric oxide-cyclic guanosine monophosphate-phosphodiesterase type 5 (NO-cGMP-PDE5) pathway in sex-specific pulmonary vascular regulation.
- To compare pulmonary hemodynamics and vasoreactivity at rest and during exercise between sexes.
Main Methods:
- In vivo assessment of pulmonary hemodynamics in male and female swine at rest and during exercise.
- In vitro studies on isolated small pulmonary arteries to evaluate vasodilation.
- Pharmacological interventions using nitric oxide synthase (NOS) and PDE5 inhibitors, alone and in combination with bradykinin.
Main Results:
- Pulmonary hemodynamics were similar between sexes at rest and during exercise.
- NOS inhibition caused comparable pulmonary vasoconstriction in both sexes.
- NOS inhibition more significantly blunted bradykinin-induced vasodilation in males than females.
- PDE5 inhibition showed similar vasodilation at rest, with a trend towards greater effect in males during exercise.
- In the presence of NOS inhibition, PDE5 inhibition produced a significantly greater vasodilator effect in females both in vivo and in vitro.
Conclusions:
- Significant sex differences exist in the regulation of pulmonary vascular tone, particularly involving the NO-cGMP-PDE5 pathway.
- These findings highlight potential mechanisms underlying sex disparities in PH incidence, severity, and treatment response.
- Further research into these sex-specific pathways could lead to more targeted therapies for pulmonary vascular diseases.
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