Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A2B receptor-K+ channel-mediated renal vasodilation

摘要

We have shown previously that the renal vasodilatory action of the adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) in female rats is mediated via preferential activation of adenosine A2B receptor (A2BR)-K+ channel signalling. In the present study, we tested the hypothesis that the renal vasodilatory effect of NECA and its A2BR/K+ channel specificities are altered by chronic nicotine administration. The oestrogenic modulation of the nicotine-NECA renovascular interaction was also evaluated by determining the effect of ovariectomy (OVX) and oestrogen replacement (OVXE2) on the evoked responses. In isolated phenylephrine-preconstricted perfused kidneys obtained from sham-operated rats, vasodilation in response to cumulative bolus injections of NECA (1.6-50 nmol) or papaverine (1-243 nmol) were not affected by nicotine (1-8 mg/kg per day, i.p., 2 weeks). However, vasodilator responses to NECA, but not papaverine, were reduced in kidneys of OVX rats and restored to near-sham values after E2 replacement. Further, nicotine increased NECA-induced vasodilation in perfused kidneys from OVX rats, but failed to do so in OVXE2 preparations. The enhanced NECA responsiveness in nicotine-treated OVX preparations was abolished after infusion (into isolated kidneys) of 10 μmol/L alloxazine (A2BR antagonist) or BaCl2 plus glibenclamide (blockers of inward rectifier and ATP-sensitive K+ channels, respectively). Vasodilator responses to 0.05-1.6 μmol minoxidil (a K+ channel opener) were increased by nicotine in OVX, but not OVXE2, preparations and this increase was abolished after infusion of BaCl2 + glibenclamide. Together, the data suggest that chronic nicotine enhances A2BR/K+ channel-mediated renal vasodilation in oestrogen-depleted rats.