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.
View: Text | PDF
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

×

Figure 8

Options: View larger image (or click on image) Download as PowerPoint
Concentration-response curves to phenylephrine in freshly dissected rat ...
Concentration-response curves to phenylephrine in freshly dissected rat renal interlobar artery rings bathed in media with (EC50, 0.06 ± 0.01A μmol/l; Rmax, 3.86 ± 0.18 mN/mm; n = 7) and without iberiotoxin (IBTX, 10 nmol/l; EC50, 0.38 ± 0.03 μmol/l; Rmax, 3.96 ± 0.11 mN/mm; n = 15), TEA (1 mmol/l; EC50, 0.10 ± 0.01A μmol/l; Rmax, 3.87 ± 0.19 mN/mm; n = 8), or TEA plus CrMP (30 μmol/l; EC50, 0.09 ± 0.01A μmol/l; Rmax, 3.83 ± 0.22 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 control.