Impaired in vivo Venous Constriction in Conscious Zucker Obese Rats

Abstract

Obesity is at present a world wide epidemic, and is associated with the development of hypertension, diabetes and coronary artery disease. Although the relationship between obesity and hypertension is recognized, the mechanism by which obesity increases blood pressure remains poorly understood. Blood pressure is a product of cardiac output (or venous return) and peripheral vascular resistance; the latter is increased in obese patients with hypertension. It is not known if obesity is associated with altered venous function. This study examined if 16 weeks old Zucker obese rats, relative to age-matched Zucker lean rats, had altered in vivo venoconstriction to norepinephrine. The obese rats, relative to the controls, had higher mean arterial pressure, body weight, plasma insulin and triglyceride, but reduced pressor and mean circulatory filling pressure (index of venous tone) responses to norepinephrine (2.5–30 × 10–9 mol/kg/min). NG-nitro-L-arginine methyl ester (8 mg/kg; inhibitor of nitric oxide synthase) did not alter mean circulatory filling pressure in either group, but increased mean arterial pressure of both groups; however, the increase was markedly less in the obese than lean rats. Therefore, the Zucker obese rats had impaired in vivo pressor and mean circulatory filling pressure responses to norepinephrine as well as reduced pressor response to NG-nitro-L-arginine methyl ester; the latter shows reduced involvement of the nitric oxide/L-arginine pathway.