Role of Endothelin-1 in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

Abstract

Purpose: : We have previously shown that choroidal blood flow regulation during isometric exercise in healthy subjects is modified by administration of an endothelin_A (ET_A) receptor antagonist. The present study tested the hypothesis that human optic nerve head blood flow (ONHBF) during isometric exercise is also modified by administration of the same ET_A receptor antagonist.

Methods: : The study was performed in 16 healthy young subjects in a randomized, placebo-controlled cross-over design. The effect of a six minutes squatting period on ONHBF was investigated without drug administration as well as during infusion of BQ-123 or placebo. ONHBF was measured using laser Doppler flowmetry. Ocular perfusion pressure (OPP) was calculated as 2/3*mean arterial pressure-intraocular pressure.

Results: : During all squatting periods OPP as well as ONHBF increased (p < 0.001 each). The increase in ONHBF was, however, less pronounced than the increase in OPP indicating for some degree of blood flow regulation. Placebo did not alter the ONHBF response to isometric exercise. BQ-123 did not alter OPP or ONHBF at baseline. The drug also did not alter the response of OPP during isometric exercise. The increase in ONHBF during squatting was, however, more pronounced than during placebo (p < 0.01). This is also evident by looking into the pressure/flow relationship. During BQ-123 administration the increase in ONHBF started at lower OPPs than during placebo administration.

Conclusions: : Our data confirm previously published observations that ONHBF under basal conditions is not altered by an ET_A receptor antagonist. Our results do, however, indicate that endothelin plays a role in the response of ONHBF during isometric exercise, providing some of the vasoconstrictor tone that counteracts the increase in OPP. Our data also show that the ONHBF response to an increase in OPP can be modified by administration of an ET_A receptor antagonist.

Clinical Trial: : http://www.clinicaltrials.gov NCT00915070

Keywords: blood supply • optic disc