Insulin attenuation of vasoconstrictor responses to phenylephrine in Zucker lean and obese rats

Recent data from this laboratory indicate that insulin resistant obese Zucker rats exhibit hypertension associated with exaggerated in vitro vascular reactivity to phenylephrine, serotonin, and KCl, and we have found insulin to attenuate vascular reactivity responses to these agonists. Accordingly, in the present study we evaluated the possibility that exaggerated vascular reactivity responses in obese Zucker rats may result from insulin resistance and a consequent failure of insulin to attenuate vasoactive responses. Thoracic aortae were isolated from male 16 week old lean and obese Zucker rats, and replicate helical strips from each animal were suspended in a muscle bath under a resting tension of 1.4 g in the presence or absence of insulin (0.1 mU/mL) for 1 h. The insulin was then washed out, and vascular reactivity responses to phenylephrine were determined. The obese rats exhibited greater reactivity to phenylephrine (ED50:1.10 +/- 90 X 10(-8) v 7.57 +/- 0.88 X 10(-10) mol/L in lean and obese rats, respectively, P less than .025). Insulin caused a significant attenuation of the contractile response in both the lean and obese aortae. However, lean rats exhibited a markedly greater attenuation than the obese rats (46.0 +/- 17.0 v 17.8 +/- 7.5% attenuation in the lean and obese rats, respectively, P less than .01). These data suggest that increased vascular reactivity responses in obese Zucker rats may result from their insulin resistant state and, consequently, a diminished ability of insulin to attenuate vasoconstrictor responses.