Differences in vasomotor function of mesenteric arteries between Ossabaw minipigs with predisposition to metabolic syndrome and Göttingen minipigs.

Metabolic syndrome predisposes and contributes to the development and progression of atherosclerosis. The minipig strain "Ossabaw" is characterized by a predisposition to develop metabolic syndrome. We compared vasomotor function in Ossabaw minipigs before they develop their diseased phenotype to that of Göttingen minipigs- without such genetic predisposition. Mesenteric arteries of adult Ossabaw and Göttingen minipigs were dissected post mortem and mounted on a myograph for isometric force measurements. Maximal vasoconstriction to potassium chloride (KClmax ) was induced. Cumulative concentration-response curves were determined in response to norepinephrine. Endothelium-dependent (with carbachol) and -independent (with nitroprusside) vasodilation were analyzed after preconstriction by norepinephrine. In a bioinformatic analysis, variants/altered base pairs within genes associated with cardiovascular disease were analyzed. KClmax was similar between the minipig strains (15.6±6.7 vs. 14.1±3.4 ΔmN). Vasoconstriction in response to norepinephrine was more pronounced in Ossabaw than in Göttingen minipigs (increase of force to 143±48 vs. 108±38% of KClmax ). Endothelium-dependent and -independent vasodilation were less pronounced in Ossabaw than in Göttingen minipigs (decrease of force to 46.4±29.6 vs. 16.0±18.4% and to 36.7±25.2 vs. 2.3±3.7% of norepinephrine-induced preconstruction). Vasomotor function was not different between the sexes. More altered base pairs/variants were identified in Ossabaw than in Göttingen minipigs for the exon encoding adrenoceptor alpha 1A. Vasomotor function in lean Ossabaw minipigs is shifted toward vasoconstriction and away from vasodilation in comparison to Göttingen minipigs, suggesting a genetic predisposition for vascular dysfunction and atherosclerosis in Ossabaw minipigs. Thus, Ossabaw minipigs may be a better model for human cardiovascular disease than Göttingen minipigs.