Nitric oxide synthase inhibition reveals differences in the nitric oxide pathway in previously laminitic ponies

Abstract

Previously laminitic (PL) ponies are reported to have higher blood pressure than non laminitic (NL) ponies. This relative hypertension may be related to endothelial cell dysfunction, similar to humans with metabolic syndrome. To investigate the relationship between laminitis predisposition and endothelial dysfunction, the effect of nitric oxide synthase (NOS) inhibition on the change in circulating nitric oxide (NO) concentrations and systemic blood pressure (BP) was determined. An intravenous NO sensor was used to measure changes in blood NO concentration during and after intravenous infusion of the NOS inhibitor L-nitroarginine methyl ester (L-NAME; 4 mg/kg IV) in PL and NL ponies. NO concentrations decreased and BP increased in response to L-NAME infusion, with a significantly (p = 0.02) greater rate of increase in systolic BP in PL (14.62 ± 1.88 mmHg/h) compared to NL (8.54 ± 1.88 mmHg/h) ponies. This greater effect on BP in PL compared to NL ponies is consistent with higher basal NO production in PL ponies, suggesting that the relative hypertension previously seen in PL ponies results in increased basal NO production, rather than being caused by reduced NO production as hypothesised. Up-regulation of the NO system may be a compensatory mechanism stimulated by the higher resting BP in PL ponies. Further investigation of the mechanism underlying the relative hypertension seen in PL ponies is required.