Abstract P304: Sex Differences in Mechanisms of Adiposity-Associated Hypertension in Dahl S Rats

Abstract

In humans, excessive accumulation of visceral adipose tissue is often associated with hypertension, but there is evidence that the mechanisms responsible may differ between men and women. Dahl S rats fed a high fat diet (HFD) from weaning gain visceral fat and develop a progressively higher arterial pressure compared to Dahl S rats fed a control diet (CD). We previously showed that the magnitude of this effect is similar in males and females. Here we used pharmacological interventions to compare in males and females the contributions of brain prostanoids, the renin-angiotensin system and the sympathetic nervous system to the development of hypertension in this rat model. Dahl S rats were placed on CD or HFD at weaning. All rats received telemetry implants at 15-16 weeks of age to measure arterial pressure, heart rate, and activity. Studies were conducted from 19-23 weeks of age, a time when hypertension is still developing. Drug interventions were separated by at least a week. Mean arterial pressure (MAP) was significantly higher in male HFD (156.0+/- 6.5 mmHg) versus male CD (133.3+/-1.6 mmHg) rats, and in female HFD (140+/-2.6 mmHg) versus female CD (131.4+/-1.2 mmHg) rats during the experimental period. Treatment for one week with the ACE inhibitor enalapril (250 mg/L in the drinking water) lowered MAP significantly more in male HFD (-38.3+/-5.9 mmHg) than in male CD (-23.9+/-1.6 mmHg) rats, but female HFD (-33.2+/-2.2 mmHg) and CD (-28.4+/-1.5 mmHg) rats responded similarly. Treatment for one week with the centrally acting sympatholytic clonidine (2 mg/L in the drinking water) reduced MAP more in females than males, but there were no differences between CD and HFD groups. One week treatment with the prostanglandin D synthase inhibitor AT56 (5.8 nmol/hr sc) caused only a slight fall in MAP (~3 mmHg) that was similar in all groups. Finally, a single injection of the ganglion blocker hexamethonium (30 mg/kg, ip) caused a short-term depressor response that was not significantly different in magnitude among the groups. We conclude that the renin-angiotensin system may have a greater role in adiposity-associated hypertension in Dahl S males versus females, but that sympathetic overactivity or prostaglandin D are not factors in either sex in the age range studied here.