The Role of Hyperinsulinemia, the Sympathetic Nervous System and Nitric Oxide in Cardiovascular Function During the Development of Obesity-Induced Hypertension.
Date of Award
Doctor of Philosophy (PhD)
David B. West
The interaction of hyperinsulinemia, the sympathetic nervous system (SNS) and nitric oxide (NO) was examined in lean and obese unilaterally lumbar sympathectomized dogs. Six lean and six obese dogs were studied while on a treadmill, during hyperinsulinemic euglycemic clamp (HIEC) procedures with and without concurrent nitric oxide synthase (NOS) inhibition with nitro-L-arginine (LNA). Changes in plasma insulin, femoral vascular resistance (FVR), heart rate (HR) and mean arterial pressure (MAP) were measured prior to and during a 7-week overfeeding period, and response to LNA administration was examined in the lean and obese state. Body weight increased from 19.9 $\pm$ 0.70 to 29.7 $\pm$ 0.77kg and % body fat from 23.0% to 48.8% during overfeeding(OF). Heart rate, MAP and plasma insulin also increased during overfeeding. Femoral vascular resistance initially increased (p $<$ 0.01 in both the intact and denervated limbs), but returned to baseline levels by OF-week 3 in the denervated limb, and by week 6 in the intact limb. No significant correlation was evident between insulin levels and other cardiovascular parameters. Hyperinsulinemic euglycemia alone did not affect MAP in either weight group. However, when hyperinsulinemia was initiated following NOS inhibition, MAP in the lean animals tended to decrease, whereas that of the obese dogs increased slightly. HR response to hyperinsulinemia (alone or concurrent with NOS inhibition) was not different between weight groups. The FVR response to hyperinsulinemia alone or with NOS inhibition was not different between the weight groups. However, heart rate and vascular response to LNA was reduced in the obese dog. In summary, sympathetic activity may influence the vascular response to weight gain. Also, hyperinsulinemia does not affect MAP, HR or FVR in lean or obese dogs, while walking slowly on a treadmill. However, when NOS is concurrently inhibited, lean and obese dogs show a tendency toward differential MAP and HR responses to hyperinsulinemia. Thus, the insulin and nitric oxide interaction may differ in lean and obese dogs, and may mediate development of hypertension in the obese population. Finally, the obese have a reduced cardiovascular response to NOS inhibition compared to the lean.
Borne, Agatha T., "The Role of Hyperinsulinemia, the Sympathetic Nervous System and Nitric Oxide in Cardiovascular Function During the Development of Obesity-Induced Hypertension." (1998). LSU Historical Dissertations and Theses. 6618.