INSULIN MODULATION OF VASCULAR REACTIVITY IS ALREADY IMPAIRED IN PREHYPERTENSIVE SPONTANEOUSLY HYPERTENSIVE RATS

Hyperinsulinemia reduces the vasoconstrictive response to norepinephrine in Wistar-Kyoto rats (WKY) but not in spontaneously hypertensive rats (SHR). It has been hypothesized that this difference in the vascular effect of insulin could be a hallmark of the hypertensive state. To test this hypothesis we studied SHR before (5 weeks old, n=10) and after (15 weeks old, n=10) the establishment of hypertension as well as two groups of age- and sex-matched WKY (5 weeks old, n=14; 15 weeks old, n=13). Blood pressure was significantly higher in SHR compared with WKY (181+/-5 versus 118+/-6 mm Hg, respectively, P<.001) in the 15-week-old rats but not in the 5-week-old rats (121+/-5 versus 117+/-3 mm Hg, P<NS). We tested vascular reactivity using increasing amounts of norepinephrine (from 10(-10)) to 10(-5) mmol/L) on isolated aortic rings in control conditions and after 30 minutes of exposure to 715 pmol/L insulin. In WKY insulin reduced the vascular response to norepinephrine in both the 5-week-old (repeated-measures ANOVA with grouping factor: F=2.443, P<.05) and 15-week old (F=9.667, P<.01) groups. In SHR at both ages insulin failed to modify the vascular response to norepinephrine (5 weeks: F=0.107, P<NS; 15 weeks: F=0.075, P<NS). Sodium nitroprusside was able to attenuate the vascular response to norepinephrine in WKY and SHR at 5 and 15 weeks. Our data demonstrate that in SHR the vascular resistance to insulin action is specific and not acquired with the hypertensive condition; thus, it seems to be a genetically inherited trait.