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ADP-induced pial arteriolar dilation in ovariectomized rats involves gap junctional communication.
H L Xu1, R A Santizo, V L Baughman
1Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|August 16, 2002
Summary
Estrogen depletion in rats maintains ADP-induced vasodilation through an endothelium-dependent hyperpolarizing factor (EDHF) mechanism, involving gap junctions and connexin43 in pial arterioles.
Area of Science:
- Physiology
- Vascular Biology
- Endocrinology
Background:
- Estrogen depletion (ovariectomy) in rats does not attenuate ADP-induced pial arteriolar dilation.
- Nitric oxide (NO) dependence is lost, suggesting a compensatory endothelium-dependent hyperpolarizing factor (EDHF)-like mechanism.
- The role of EDHF in estrogen-depleted females requires further characterization, particularly regarding endothelial dependence and gap junction involvement.
Purpose of the Study:
- To investigate the endothelial dependence of ADP-induced pial arteriolar dilation in ovariectomized (Ovx) rats.
- To determine the involvement of gap junctions in this response in Ovx rats.
- To elucidate the specific mechanisms replacing nitric oxide (NO) signaling in estrogen-depleted female rats.
Main Methods:
- Utilized a closed cranial window and intravital microscopy to measure pial arteriolar diameter changes in anesthetized rats.
- Assessed endothelial dependence using light dye endothelial injury (L/D).
- Investigated the roles of NO and prostanoids using inhibitors (L-NNA, Indomethacin) and evaluated gap junction involvement with Gap 27 and connexin43 antisense oligonucleotides.
Main Results:
- Endothelial injury reduced ADP-induced dilation by 50-70% in both intact and Ovx rats, confirming retained endothelial dependence.
- In intact rats, NO/prostanoid inhibition partially reduced the response, while in Ovx rats, NO/prostanoid independence was observed, highlighting EDHF.
- Gap junction inhibition (Gap 27, connexin43 antisense) significantly reduced ADP-induced dilation in Ovx rats but not in intact rats.
Conclusions:
- Chronic estrogen depletion does not alter the endothelial dependence of ADP-induced pial arteriolar vasodilation.
- In estrogen-depleted rats, ADP-induced dilation relies on an EDHF mechanism independent of NO and prostanoids.
- Connexin43-related gap junction communication is crucial for the nascent EDHF-mediated ADP-induced pial arteriolar dilation in Ovx females.