gms | German Medical Science

Inbred Wistar rats homozygous for the RT1U MHC haplotype (WOKW) show obesity, hypertriglyceridemia, hyperinsulinemia and impaired glucose tolerance. Coronary and skeletal muscle (A. gracilis) artery function were characterized by small vessel myography in 3- and 10-months-old WOKW to test if they are suitable to study vascular dysfunction in metabolic syndrome. Dark Agouti (DA) rats served as lean controls. Norepinephrine (NE) increased coronary wall tension in WOKW to 22% of maximum K+-induced tension. DA coronaries did not contract in response to NE (p < 0.001). Maximum vasopressin (AVP)-induced tension in WOKW was 190% vs. 120% of maximum K+ induced tension in DA (p < 0.001). Respective data were similar in 10-months-old rats. Coronary responses to endothelin-1 were similar in both strains. Acetylcholine- and isoproterenol-induced coronary dilation were similar in WOKW and DA at either age. Phenylephrine (PE) mimicked the strain differences in NE-induced coronary contraction. Enhanced PE- and AVP-induced coronary contraction did not depend on extracellular Ca2+. Rho-kinase inhibition almost abolished PE-induced contraction in WOKW. AVP-induced contraction was blunted to a similar degree by rho-kinase inhibition in either strain. Maximum skeletal muscle artery dilation in response to acetylcholine and Na-nitroprusside was less in DA than in WOKW (p < 0.01) while insulin-induced gracilis artery dilation was similar in WOKW and DA at either age. Proteinuria (mg/100g bw * 24h) was higher in WOKW than in DA at 3 (6.9 ± 0.43 vs 4.4 ± 0.5) and 10 months (6.3 ± 0.3 vs. 4.7 ± 0.5) of age (p < 0.001). At 10 months of age mean arterial pressure was virtually identical in animals of either strain (111 ± 3 mmHg in WOKW, 111 ± 4 mmHg in DA).

The present data indicate that despite obesity, elevated plasma triglycerides and hyperinsulinemia vascular function does not show enhanced deterioration in WOKW compared to a lean inbred rat strain up to 10 months of age.