No abstract

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.

We previously showed that the renal vasodilatory action of the adenosine analog 5’‐N‐ethyl carboxamidoadenosine (NECA) in female rats is mediated via adenosine A2B receptors (A2BRs) and is facilitated by estrogen (E2). We tested the hypothesis that renal NECA vasodilation and its estrogen and A2BR specificities are altered by chronic nicotine. Cumulative NECA (1.6–50 nmol) or papaverine (1‐243 nmol) vasodilations were not affected by nicotine (1‐8 mg/kg/day i.p., 2 weeks) in isolated phenylephrine‐preconstricted perfused kidneys of sham preparations. NECA, but not papaverine, vasodilations were reduced in kidneys of ovariectomized (OVX) rats and restored to near‐sham values after E2 replacement. Further, nicotine increased NECA vasodilations in OVX preparations in contrast to no effect in sham or OVXE2 kidneys. The enhanced NECA responsiveness in nicotine‐treated OVX preparations was abolished after the infusion of alloxazine (A2BR antagonist) or BaCl2 plus glibenclamide (blockers of inward rectifier and ATP‐sensitive K+ channels, respectively). Moreover, vasodilations caused by minoxidil (K+‐channel opener) were increased by nicotine in OVX, but not sham or OVXE2, preparations and this increase was abolished after BaCl2/glibenclamide infusion. Together, estrogen compromises the enhancing effect of nicotine on renal vasodilations evoked via the activation of the A2BR/K+ channel cascade. Grant Funding Source: Supported by STDF ID 502, Egypt