Impaired coronary function in Wistar Ottawa Karlsburg W rats-a new model of the metabolic syndrome.

The metabolic syndrome is associated with an increased risk for coronary heart disease. The underlying mechanisms are not well understood. The present study was designed to investigate coronary function in Wistar Ottawa Karlsburg W (WOKW) rats, a new animal model of the metabolic syndrome. The responses of coronary artery segments from WOKW and Dark Agouti (DA) control rats of different ages to several physiological vasoconstrictors and vasodilators were measured in a small vessel wire myograph, and potential mechanisms involved in the differential responses between the two strains were investigated. WOKW showed increased alpha(1)-adrenoceptor-mediated coronary constriction at 3 and 10 months of age, as well as seriously blunted beta-adrenoceptor-mediated coronary relaxation at 16 months of age. Responses to non-adrenergic agonists were not altered in WOKW compared to DA. The alpha(1)-adrenoceptor-mediated coronary constriction in WOKW was completely blocked by rho-kinase inhibition. Induced hyperinsulinemia did not cause increased alpha(1)-adrenoceptor-mediated coronary constriction or impaired beta-adrenoceptor-mediated coronary relaxation in DA. The association between blunted coronary beta-adrenoceptor responsiveness and the metabolic syndrome was confirmed in Zucker diabetic fatty rats. We conclude that the metabolic syndrome in WOKW rats is associated with impaired coronary function due to altered adrenoceptor sensitivity. The latter may contribute to inappropriately elevated coronary tone in insulin-resistant subjects, especially when sympathetic activity to the heart is increased.