Key Points
- To determine sex differences in cardiac norepinephrine release and presynaptic alpha 2-adrenergic inhibition during normal oxygen levels and early ischemia.
- Evaluated sympathetic nerve stimulation-evoked norepinephrine release and functional responses in isolated perfused innervated rat hearts under normoxic and stop-flow ischemic conditions.
- Assessed presynaptic alpha 2-adrenoceptor function using the selective antagonist rauwolscine, and examined the role of female hormones using ovariectomized and sham-operated female rats.
- Under normoxia, rauwolscine produced a significantly greater increase in norepinephrine overflow (p < 0.05) and heart rate/contractility responses (p < 0.01) in females compared with males.
- During early stop-flow ischemia, neural norepinephrine overflow was significantly lower in females than in males (p < 0.005), a disparity eliminated by rauwolscine administration (p < 0.05).
- Ovariectomy significantly reduced presynaptic alpha 2-adrenergic inhibition compared to sham-operated controls (p < 0.02), while baseline cardiac norepinephrine stores showed no sex differences.
Structured PICO
PPopulationPerfused innervated rat heart model (male and female rats, including ovariectomized and sham-operated females)
IInterventionAlpha 2-adrenoceptor antagonist rauwolscine during normoxic perfusion and early stop-flow ischemia; ovariectomy in females
CComparatorMale rats vs. female rats; sham-operated females vs. ovariectomized females
OOutcomeSympathetic nerve stimulation-induced norepinephrine release/overflowsurrogate
Female hormones may increase presynaptic alpha 2-adrenergic activity in the heart, leading to greater inhibition of myocardial norepinephrine release in female rats compared to males during both normoxia and ischemia.