Elevated sympathetic activity contributes to hypertension and salt sensitivity in diabetic obese Zucker rats

Zucker rats are a useful model in which to define the mechanisms that link obesity to diabetes and associated cardiovascular disease. The present stud y tests the hypothesis that diabetic obese (compared with nondiabetic lean) Zucker rats are hypertensive and display a further increase in arterial pr essure when fed a high salt diet. Male, nondiabetic lean and diabetic obese Zucker rats were chronically instrumented with telemetry probes and fed a basal salt diet for 3 weeks followed by exposure to a high salt diet for 11 days. On the basal diet, obese (vs lean) rats had significantly higher art erial pressures (approximate to 13 mm Hg), and the high salt diet significa ntly elevated mean arterial pressure (MAP) in obese (but not lean) Zucker r ats (approximate to 12 mmHg). Blockade of the sympathetic nervous system wi th hexamethonium caused a significantly larger decrease in MAP in obese (vs lean) Zucker rats fed the basal diet (51 vs 33 mm Hg), but the high salt d iet did not increase: the hexamethonium-induced reduction in arterial press ure in obese rats. Acute blockade of angiotensin receptors with losartan re sulted in similar decreases in MAP in both groups on either diet. Acetylcho line-induced vasodilatory capacity of the carotid artery was significantly less in the obese (vs lean) Zucker rats. Together these data indicate that increased sympathetic nervous system activity and decreased vascular reacti vity may contribute to elevated arterial pressure in type 2 diabetic, obese Zucker rats, but the sympathetic nervous system does not appear to contrib ute to the dietary salt-sensitive hypertension in this model.