Nascent EDHF-mediated cerebral vasodilation in ovariectomized rats is not induced by eNOS dysfunction

Area of Science:

• Cardiovascular Physiology
• Neuroendocrinology

Background:

• Estrogen depletion (ovariectomy) in female rats leads to an endothelium-derived hyperpolarizing factor (EDHF)-like mechanism potentially compensating for reduced nitric oxide (NO).
• Estrogen replacement restores endothelial NO synthase (eNOS) function and diminishes EDHF activity in these animals.
• The study investigates if the increased EDHF role in estrogen-depleted rats is due to chronically repressed eNOS function.

Purpose of the Study:

• To determine if the enhanced EDHF-like activity in estrogen-depleted (ovariectomized) female rats is linked to chronically repressed endothelial nitric oxide synthase (eNOS)-derived NO production.
• To examine the direct effect of estrogen on EDHF-mediated cerebral vasodilation.

Main Methods:

• Chronic inhibition of NO synthase (NOS) using N-nitro-L-arginine methyl ester (L-NAME) in anesthetized intact, ovariectomized (Ovx), and estrogen-treated Ovx (OVE) female rats, as well as male rats.
• Pial arteriolar vasodilation was assessed using acetylcholine (ACh) and adenosine diphosphate (ADP) in the presence or absence of indomethacin (Indo) and the gap junction blocker Gap 27.
• Carbon dioxide (CO2) reactivity was also measured.

Main Results:

• Acetylcholine-induced vasodilation was impaired in Ovx rats but partially recovered with L-NAME treatment, suggesting a role for NOS in its regulation.
• ADP-induced dilation in estrogen-depleted rats, after NOS and cyclooxygenase inhibition, was significantly attenuated by Gap 27, indicating EDHF involvement.
• Nitric oxide (NO) did not inhibit EDHF production or action in the cerebral microcirculation, and the increased EDHF activity in Ovx rats was not due to eNOS deficiency.

Conclusions:

• Cerebral microcirculation vasodilation in estrogen-depleted rats involves an EDHF-like mechanism that is not suppressed by NO.
• The enhanced EDHF activity in estrogen deficiency is not caused by a lack of eNOS function.
• Estrogen appears to directly modulate EDHF-mediated cerebral vasodilation, independent of its effects on eNOS.