Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A2B receptor-K(+) channel-mediated renal vasodilation.
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 (A2B R)-K(+) channel signalling. In the present study, we tested the hypothesis that the renal vasodilatory effect of NECA and its A2B R/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 (A2B R 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 A2B R/K(+) channel-mediated renal vasodilation in oestrogen-depleted rats.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Mahmoud M
MM
El-Mas
Sahar M
SM
El-Gowilly
Lamia K
LK
Elsalakawy
Hanan M
HM
El-Gowelli
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D010052:Ovariectomy / Q000379:methods; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D004967:Estrogens; D015221:Potassium Channels; D043704:Receptor, Adenosine A2B; D014665:Vasodilator Agents; D010656:Phenylephrine; D019830:Adenosine-5'-(N-ethylcarboxamide); D009538:Nicotine
K+ channels; adenosine A2B receptors; nicotine; oestrogen; ovariectomy; perfused kidney