Key Points
- To examine sex differences in protein kinase G (PKG) activity and the modulating roles of the endothelium and oestrogen in rat thoracic aortic rings.
- Measured isometric tension in phenylephrine-preconstricted (0.1 microM) aortic rings from intact male, intact female, and ovariectomized female rats treated with vehicle or oestrogen.
- Evaluated relaxation responses to PKG subtype-selective cGMP analogues (8-Br-PET-cGMP for PKG 1alpha and 8-APT-cGMP for PKG 1beta) in the presence or absence of endothelium, guanylate cyclase inhibitor ODQ (1 microM), and NOS inhibitor L-NMMA (100 microM).
- Phenylephrine constriction was greater in male than female aortas, a difference attenuated by endothelial removal, ODQ, or L-NMMA, reflecting higher basal NO production in females.
- Aortas from male rats showed significantly greater relaxation responses than females to both cGMP analogues, with 8-Br-PET-cGMP demonstrating higher potency than 8-APT-cGMP across both sexes.
- Endothelial removal and ODQ eliminated the sex difference in 8-APT-cGMP relaxation, whereas L-NMMA did not; furthermore, oestrogen replacement in ovariectomized rats failed to alter constriction or PKG-mediated relaxation in the presence of ODQ.
Structured PICO
PPopulationRat thoracic aortic rings from control male and female rats, and ovariectomized female rats
IInterventionOestrogen treatment (in ovariectomized rats) and PKG activation with cGMP analogues (8-Br-PET-cGMP and 8-APT-cGMP)
CComparatorVehicle treatment (in ovariectomized rats) and male vs female aortas
OOutcomeVasorelaxation response and PKG activitysurrogate
Female rat aortas have greater basal NO production, but male aortas show greater relaxant responses to PKG activation, a difference not explained by oestrogen.