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In an effort to understand obesity associated hypertension, we and others are using Dahl salt-sensitive (SS) rats fed a high fat diet as an experimental model. One reason for choosing this rat strain is that it is well-known that SS rats exhibit accelerated hypertension development not just in response to high salt intake but to numerous other stimuli as well, when compared to Dahl salt resistant (SR) rats. However, it is not known whether this general dichotomous sensitivity to hypertension development in SS and SR rats also extends to the impact of high fat feeding. Therefore, in the present study we tested the hypothesis that high fat feeding would cause a smaller increase in blood pressure in SR rats versus SS rats in both females and males (n=8 each). To explore possible strain differences in the mechanisms known to contribute to obesity associated hypertension, we also compared the activity of the renin angiotensin and sympathetic nervous systems in SS and SR rats. Rats were fed a high fat diet (60% kcal fat) from weaning. Blood pressure was measured by telemetry starting at 12 weeks of age. At 12 weeks, mean arterial pressures (MAP, mmHg) were 109±8 and 158±6 in male SR and SS rats, and 108±1 and 150±5 in female SR and SS rats, respectively. By 18 weeks MAP were 109±7 and 175±4 in male SR and SS rats, and 108±1 and 180±4 in female SR and SS rats, respectively. In males, plasma renin was lower, and aldosterone the same, in SS rats than SR rats. However, SS rats showed larger falls in blood pressure during week-long ACE inhibitor treatment and to acute sympathoinhibition with hexamethonium than did SR rats. In females, plasma renin and aldosterone both were higher in SS rats than SR rats. Female SS rats also showed larger falls in blood pressure to chronic ACE inhibition and acute ganglion blockade than did SR rats. These results confirm that both male and female SR rats are highly resistant to obesity associated hypertension, and that less robust activation by high fat diet of the renin angiotensin and sympathetic nervous systems may be a causative factor.

Dahl salt-sensitive (SS) and salt-resistant (SR) rats show dramatically different blood pressure (BP) responses to being raised on a high fat, but normal salt, diet starting at weaning. Virtually no effect on BP is seen in SR rats, whereas in SS rats mean arterial pressure (MAP) reaches over 160 mmHg by adulthood. The BP difference is similar in female and male rats. The cellular and physiological mechanisms responsible have not been completely elucidated in either sex. Dysfunctional perivascular adipose tissue (PVAT) is proposed to contribute to obesity-associated hypertension through actions on other components of the vascular wall. Here we used female rats to test the hypothesis that differences in adipose tissue amount or function in SS and SR rats play a part in the distinct BP effects of high fat diet in the two strains. Rats (n=8 per strain) were fed a high fat diet (60% kcal fat) from weaning. BP was measured with telemetry. At 18 weeks of age, MAPs (mmHg) were 108±1 and 180±4 in SR and SS rats. Body weights (g) were 274±4 and 323±4. Total and visceral adipose volumes (mm3) measured by μCT were higher in SS rats versus SR rats (visceral: 22372±927 versus 14112±1495; total: 17208±732 versus 10234±984). PVAT volume around the thoracic aorta was larger in SS rats (0.228±0.017 versus 0.167±0.006). Subcutaneous adipose tissue volumes did not differ. Plasma triglycerides and cholesterol were modestly but significantly higher in SS rats. The well-known anticontractile effect of PVAT was compared in thoracic aorta from both strains. Removal of PVAT increased the AUC of the tension/PE contraction in SR rats by 1484±226 units and by a significantly smaller amount (946±162.5 units) in SS rats. Finally, aortic stiffness was estimated from pulse wave velocity measured via Doppler in a subset (n=4 each) of rats from each strain. Pulse wave velocity (M/sec) was markedly higher in SS than SR rats (11.5±1.0 versus 6.4±0.3). We conclude that differences in adipose tissue volume, location or function could account in part for the distinct BP responses of female SS and SR rats to high fat feeding.