Vasomotor Reaction to Cyclooxygenase-1-Mediated Prostacyclin Synthesis in Carotid Arteries from Two-Kidney-One-Clip Hypertensive Mice.

Bin Liu, Zhenhua Li, Yingzhan Zhang, Wenhong Luo, Jiling Zhang, Hui Li, Yingbi Zhou

PloS one 2015

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This study tested the hypothesis that in hypertensive arteries cyclooxygenase-1 (COX-1) remains as a major form, mediating prostacyclin (prostaglandin I2; PGI2) synthesis that may evoke a vasoconstrictor response in the presence of functional vasodilator PGI2 (IP) receptors. Two-kidney-one-clip (2K1C) hypertension was induced in wild-type (WT) mice and/or those with COX-1 deficiency (COX-1-/-). Carotid arteries were isolated for analyses 4 weeks after. Results showed that as in normotensive mice, the muscarinic receptor agonist ACh evoked a production of the PGI2 metabolite 6-keto-PGF1α and an endothelium-dependent vasoconstrictor response; both of them were abolished by COX-1 inhibition. At the same time, PGI2, which evokes contraction of hypertensive vessels, caused relaxation after thromboxane-prostanoid (TP) receptor antagonism that abolished the contraction evoked by ACh. Antagonizing IP receptors enhanced the contraction to the COX substrate arachidonic acid (AA). Also, COX-1-/- mice was noted to develop hypertension; however, their increase of blood pressure and/or heart mass was not to a level achieved with WT mice. In addition, we found that either the contraction in response to ACh or that evoked by AA was abolished in COX-1-/- hypertensive mice. These results demonstrate that as in normotensive conditions, COX-1 is a major contributor of PGI2 synthesis in 2K1C hypertensive carotid arteries, which leads to a vasoconstrictor response resulting from opposing dilator and vasoconstrictor activities of IP and TP receptors, respectively. Also, our data suggest that COX-1-/- attenuates the development of 2K1C hypertension in mice, reflecting a net adverse role yielded from all COX-1-mediated activities under the pathological condition.

Citation

Bin Liu, Zhenhua Li, Yingzhan Zhang, Wenhong Luo, Jiling Zhang, Hui Li, Yingbi Zhou. Vasomotor Reaction to Cyclooxygenase-1-Mediated Prostacyclin Synthesis in Carotid Arteries from Two-Kidney-One-Clip Hypertensive Mice. PloS one. 2015;10(8):e0136738