Balloon catheter injury abolishes phenylephrine-induced relaxation in the rat contralateral carotid

Abstract

Background and purpose: The consequences of compensatory responses to balloon catheter injury in rat carotid artery, on phenylephrine-induced relaxation and contraction in the contralateral carotid artery were studied.

Experimental approach: Relaxation and contraction concentration-response curves for phenylephrine were obtained for contralateral carotid arteries in the presence of indomethacin (COX inhibitor), SC560 (COX-1 inhibitor), SC236 (COX-2 inhibitor) or 4-hydroxytetramethyl-L-piperidine-1-oxyl (tempol; superoxide dismutase mimetic). Reactive oxygen species were measured in carotid artery endothelial cells fluorimetrically with dihydroethidium.

Key results: Phenylephrine-induced relaxation was abolished in contralateral carotid arteries from operated rats (E(max) = 0.01 ± 0.004 g) in relation to control (E(max) = 0.18 ± 0.005 g). Phenylephrine-induced contractions were increased in contralateral arteries (E(max) = 0.54 ± 0.009 g) in relation to control (E(max) = 0.38 ± 0.014 g). SC236 restored phenylephrine-induced relaxation (E(max) = 0.17 ± 0.004 g) and contraction (E(max) = 0.34 ± 0.018 g) in contralateral arteries. Tempol restored phenylephrine-induced relaxation (E(max) = 0.19 ± 0.012 g) and contraction (E(max) = 0.42 ± 0.014 g) in contralateral arteries, while apocynin did not alter either relaxation (E(max) = 0.01 ± 0.004 g) or contraction (E(max) = 0.54 ± 0.009 g). Dihydroethidium fluorescence was increased in contralateral samples (18 882 ± 435 U) in relation to control (10 455 ± 303 U). SC236 reduced the fluorescence in contralateral samples (8250 ± 365 U).

Conclusions and implications: Balloon catheter injury abolished phenylephrine-induced relaxation and increased phenylephrine-induced contraction in contralateral carotid arteries, through O(2) (-) derived from COX-2.

Figure 1

Concentration-dependent responses to phenylephrine in endothelium-intact (E+) control or contralateral carotid arteries, and in endothelium-denuded (E−) ipsilateral carotid arteries. (A) Representative records of phenylephrine-induced relaxation (10⁻¹⁵–10⁻¹⁰ mol·L⁻¹); (B) representative records of phenylephrine-induced contraction (10⁻¹⁰–10⁻⁵ mol·L⁻¹); (C) Concentration–response curves for phenylephrine-induced relaxation and contraction.

Figure 2

Concentration–response curves for phenylephrine-induced relaxation or contraction in endothelium-intact (E+) or endothelium-denuded (E−) control or contralateral carotid arteries.

Figure 3

Concentration–response curves for phenylephrine-induced relaxation or contraction in endothelium-intact control or contralateral carotid arteries in the absence (no pretreatment) or presence of COX inhibitors. (A) Pretreatment with indomethacin. (B) Pretreatment with SC560. (C) Pretreatment with SC236.

Figure 4

Concentration–response curves for phenylephrine-induced relaxation or contraction in endothelium-intact control or contralateral carotid arteries in the absence (no pretreatment) or presence of tempol.

Figure 5

Concentration–response curves for phenylephrine-induced relaxation or contraction in endothelium-intact control or contralateral carotid arteries in the absence (no pretreatment) or presence of apocynin.

Figure 6

Cytofluorographic analysis of the fluorescence emitted by blank or dihydroethidium (DHE)-leaded samples of endothelial cells from control and contralateral carotid arteries in the absence or presence of tiron or SC236. Significant difference (P < 0.001) compared with the blank samples from control endothelial cells (*), blank samples from contralateral endothelial cells (**), and from DHE samples of control endothelial cells in the absence of tiron or SC236 (#), DHE samples from contralateral endothelial cells in the absence of tiron or SC236 (##), DHE samples from control endothelial cells in the presence of tiron (§) or DHE samples from control endothelial cells in the presence of SC236 (§§).