Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors
Jun-Ichi Kaide, … , Nader G. Abraham, Alberto Nasjletti
Jun-Ichi Kaide, … , Nader G. Abraham, Alberto Nasjletti
Published May 1, 2001
Citation Information: J Clin Invest. 2001;107(9):1163-1171. https://doi.org/10.1172/JCI11218.
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Article

Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors

Abstract

Rat renal interlobar arteries express heme oxygenase 2 (HO-2) and manufacture carbon monoxide (CO), which is released into the headspace gas. CO release falls to 30% and 54% of control, respectively, after inhibition of HO activity with chromium mesoporphyrin (CrMP) or of HO-2 expression with antisense oligodeoxynucleotides (HO-2 AS-ODN). Patch-clamp studies revealed that CrMP decreases the open probability of a tetraethylammonium-sensitive (TEA-sensitive) 105 pS K channel in interlobar artery smooth muscle cells, and that this effect of CrMP is reversed by CO. Assessment of phenylephrine-induced tension development revealed reduction of the EC50 in vessels treated with HO-2 AS-ODN, CrMP, or TEA. Exogenous CO greatly minimized the sensitizing effect on agonist-induced contractions of agents that decrease vascular CO production, but not the sensitizing effect of K channel blockade with TEA. Collectively, these data suggest that vascular CO serves as an inhibitory modulator of vascular reactivity to vasoconstrictors via a mechanism that involves a TEA-sensitive K channel.

Authors

Jun-Ichi Kaide, Fan Zhang, Yuan Wei, Houli Jiang, Changhua Yu, WenHui Wang, Michael Balazy, Nader G. Abraham, Alberto Nasjletti

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Effect of exogenous CO on phenylephrine-induced contraction of rat renal...
Effect of exogenous CO on phenylephrine-induced contraction of rat renal interlobar artery rings maintained in organ culture for 18 hours prior to experimentation in media containing both HO-1 AS-ODN (40 μg/ml) and HO-2 AS-ODN (40 μg/ml) (a) or the corresponding scrambled oligodeoxynucleotides (HO-1 S-ODN and HO-2 S-ODN, both at 40 μg/ml) (b). (a) HO-1 AS-ODN + HO-2 AS-ODN without CO (EC50, 0.16 ± 0.02 μmol/l; Rmax, 4.24 ± 0.37 mN/mm; n = 9), with 0.1 μmol/l CO (EC50, 0.53 ± 0.06A μmol/l; Rmax, 4.14 ± 0.29 mN/mm; n = 9). and with 1.0 μmol/l CO (EC50, 0.84 ± 0.10A μmol/l; Rmax, 4.08 ± 0.33 mN/mm; n = 9). (b) HO-1 S-ODN + HO-2 S-ODN without CO (EC50, 0.52 ± 0.06 μmol/l; Rmax, 4.31 ± 0.16 mN/mm; n = 8), with 0.1 μmol/l CO (EC50, 0.49 ± 0.07 μmol/l; Rmax, 4.27 ± 0.19 mN/mm; n = 8), and with 1.0 μmol/l CO (EC50, 0.47 ± 0.06 μmol/l; Rmax, 4.29 ± 0.18 mN/mm; n = 8). L-NAME (1 mmol/l) was included in the buffer used in contractility studies. Results are mean ± SEM. AP < 0.05 relative to corresponding data in vessels not exposed to exogenous CO.