Acute antihypertensive response to tempol in the SHR depends on ATP‐sensitive potassium channel (K ATP ), but not large‐conductance Ca2+‐activated potassium (BK) channels

Abstract

Acute intravenous (IV) administrations of the piperidine nitroxides reduce BP and heart rate (HR) in SHR in proportion to their superoxide dismutase (SOD) mimetic activity. Blockade of nitric oxide synthase (NOS) blunted 40% of the fall in MAP with IV tempol whereas blockade of ganglionic sympathetic neurotransmission with hexamethonium blunted 40% of the fall in MAP, and combined blockade blunted about 80% of the fall in BP. Central administration of tempol was ineffective. Here, we tested the hypothesis that the tempol activates potassium conductances in vivo. Tempol caused dose-dependent reductions in MAP and HR maximal at 174 μmol/kg (ΔMAP −56 ± 4 mmHg and ΔHR −34 ± 5 min−1, n=7). Activation of KATP channel with cromakalim (50 μg iv bolus and 50 μg /hr, iv), with coinfusion of norepinephrine to restore BP toward control level significantly reduced tempol antihypertensive response by 40% (at 174 μmol/kg, ΔMAP −33 ± 5 mmHg, p < 0.01), whereas blockade of KATP channels with glibenclamide (15 mg/kg) significantly reduced tempol antihypertensive response by 31% (ΔMAP −46 ± 10 vs. control −67 ± 8 mmHg, n=6; p<0.01). In contrast, inhibition of BK channels with iberiotoxin (100 and 300 μg/kg, n=6) did not affect tempol’s antihypertensive effect. In conclusion, the acute antihypertensive response to IV tempol is mediated via potentiation of NO, reduction in sympathetic tone and activation of KATP, but not BK channels.