Plasma Vasoprotective Eicosanoid Concentrations in Healthy Greyhounds and Non-Greyhound Dogs

Abstract

Background: Hypertension and albuminuria often coexist in Greyhounds, suggesting generalized vascular dysfunction that could contribute to the development of a variety of diseases in this breed. Eicosanoid metabolites of arachidonic acid (AA) mediate endothelial function, vascular reactivity, and proteinuria in humans and in rodent models. Hypothesis: The eicosanoid profile of Greyhounds is shifted toward metabolites that promote vascular dysfunction, hypertension, and proteinuria. Animals: Healthy Greyhounds (n = 20) and non-Greyhound (n = 20) dogs that were consecutively enrolled in a blood donor program. Methods: Prospective study. Plasma eicosanoid metabolites were assayed by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI/MS) and compared to systolic blood pressure (SP) measurements and urine albumin concentration. Results: Isomers of hydroxyeicosatetraenoic acid (HETE) were higher in Greyhounds than non-Greyhounds (median, range in pmol/mL: 5(S)HETE 19.82, 8.55-32.95 versus 13.54, 4.33-26.27, P = .033; 8(S)HETE 9.39, 3.28-19.84 versus 5.80, 2.25-17.66, P = .002; 9(S)HETE 9.46, 2.43-13.79 versus 5.82, 1.50-17.16, P = .026; 12(S)HETE 10.17, 3.81-40.06 versus 7.24, 2.9-16.16, P = .022). Dihydroxyeicosatrienoic acid (DHET) isomers also were higher in Greyhounds compared to non-Greyhounds (mean ± SD in pmol/mL: 8,9DHET 5.78 ± 2.13 versus 4.03 ± 1.36, P = .004; 11,12DHET 11.98 ± 2.86 versus 8.90 ± 3.48, P = .004; 14,15DHET 7.23 ± 2.19 versus 5.76 ± 1.87, P = .028). Albuminuria correlated with total DHET (rs = 0.46, P = .003). SP was positively correlated with 11,12EET (rs = 0.42, P = .006) and 20(S)HETE (rs = 0.38, P = .017). SP and 8,9EET were inversely correlated (rs = -0.49, P = .001). Conclusions and Clinical Importance: Plasma eicosanoid profile in Greyhounds was consistent with activation of metabolic pathways known to promote vascular dysfunction and might contribute to higher blood pressures and albuminuria. Inhibition of these eicosanoid pathways should be evaluated as therapeutic targets in Greyhounds.