Arterial hypertension induces ocular vascular dysfunction in mice with pressure-overload cardiac hypertrophy

Abstract

Purpose : The etiology and mechanism of hypertensive retinopathy are not fully understood. Transverse aortic coarctation (TAC) between the two common carotid arteries (CCA) elicits cardiac hypertrophy and 40-50% increase in blood pressure to the right CCA, but its impact on the ocular circulation is unknown. The present study was aimed at using the TAC model to investigate whether arterial hypertension causes retinal injury.

Methods : TAC was performed in mice by banding the aorta between the left CCA and the right brachiocephalic artery, which gives rise to the right CCA. Sham-operated mice served as controls. Blood velocity in CCA and central retinal artery (CRA) was measured by Doppler ultrasound. Ophthalmic arteries were isolated, cannulated and pressurized to 75 cmH₂O for functional study. Retinal morphology was examined using fundus imaging, optical coherence tomography, and histology.

Results : Induction of TAC for one month caused left ventricular hypertrophy and dysfunction. Blood velocity in the right CCA was increased by 50% after one week of aortic banding. However, velocity change in the right CRA lagged behind and slowly increased by 50% at 4 weeks post-operation. Blood velocity in the left CCA was decreased by 50% after one week of aortic banding, but the corresponding velocity in the CRA was decreased only by 20% and reached a steady level after 4 weeks of banding. The responses of right (hypertensive) ophthalmic arteries to the endothelium-dependent, nitric oxide-mediated vasodilators acetylcholine and adenosine were significantly reduced and the vasoconstriction to endothelin-1 was increased after 4 weeks of aortic banding. In contrast, the responses of left ophthalmic (hypotensive) arteries to the above agonists were unchanged. There were no marked changes in retinal morphology in both eyes.

Conclusions : Elevated right CCA blood pressure leads to a corresponding increase in flow velocity in both carotid artery and CRA. The elevation of blood pressure and flow for 4 weeks causes ophthalmic vascular dysfunction without altering retinal morphology. The ophthalmic vasomotor function is insensitive to hypotensive insult, and blood flow in the CRA appears to be regulated during hypotension to minimize hypoperfusion. The hypertension-induced ophthalmic vascular changes may lead to dysregulation of ocular blood flow and consequent retinal injury.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.