Constriction of porcine retinal arterioles induced by endothelin‐1 and the thromboxane analogue U46619 in vitro decreases with increasing vascular branching level

Abstract

ABSTRACT.Purpose: The retinal blood flow depends on the diameter of retinal arterioles, but diameter changes in these vessels have hitherto only been assessed in vessels larger than approximately 100 lm. Therefore, a new method was developed for studying diameter changes along the vascular tree of arterioles in whole perfused segments of porcine retinas, and the effect of known vasoconstrictors on the diameter of retinal arterioles at different branching levels were studied. Methods: Thirty-four whole-mounted porcine retinas were placed in a specially designed tissue chamber. On the basis of video recordings through an inverted microscope, the diameter of retinal arterioles was measured at five different branching levels before and after addition of a high potassium concentration, or increasing concentrations of endothelin-1, the prostaglandin analogue U46619, noradrenaline or none (time controls). Results: The baseline diameter ranged from 136 lm (95% CI 132-140 lm) for 1st order arterioles to 33 lm (95% CI 21-44 lm) for 5th order arterioles. In 1st order arterioles, endothelin produced 56.6% (95% CI 47.6-64.0) and U46619 14.6% (95% CI 5.7-22.6) relative constriction compared with baseline, which for both compounds decreased significantly with increasing branching level (p < 0.0001 and p < 0.0001, respectively). The change in diameter during addition of noradrenaline did not differ significantly from the time controls (p = 0.07). Conclusions: The effect of retinal vasoconstrictors differs among larger and smaller arterioles. The study highlights the need for investigating diameter regulation in smaller retinal arterioles as a basis for understanding normal and pathological changes in retinal blood flow.

The vasodilating effects of insulin and lactate are increased in precapillary arterioles in the porcine retina ex vivo

“…) and on the first arteriolar branchings (Torring et al. ), but does not reach the level of complexity in models of whole perfused retinas developed for the study of retinal function ex vivo (Niemeyer ; Luke et al. ).…”

“…Approximately twice the reported number of experiments were conducted because vessels were discarded if U46619‐induced constriction had obliterated the vascular lumen, so that intravascularly added compounds could not pass the retinal vascular system, if KPSS resulted in a less than 10% constriction of arterioles so that the vessel could be considered to be non‐viable (Torring et al. ), if the vessels leaked fluorescence or if an air bubble inadvertently passed the vessels in the preparation.…”

“…Thus, the contraction induced by the thromboxane analogue U46619 known to target cells in the vascular wall (Bek & Holmgaard ) has been shown to differ among smaller and larger retinal arterioles in vitro (Torring et al. ), and lactate has been demonstrated to have vasoactive effects on pericyte containing retinal microvessels (Yamanishi et al. ).…”

Diabetic macular ischaemia is associated with narrower retinal arterioles in patients with type 2 diabetes

“…It is also important to note that our observations are not due to vasoconstriction from topical dilating drops, as these have been found to not influence vessel calibres (Vandewalle et al 2013). Further research on DMI could focus on using other non-invasive haemodynamic measurement techniques (Pemp et al 2013) and measuring vessel calibres at different points in the vascular branching network, which may be differently affected (Torring et al 2014).…”

“…) and measuring vessel calibres at different points in the vascular branching network, which may be differently affected (Torring et al. ).…”