Reduced plasma volume and mesenteric vascular reactivty in obese Zucker rats

Schreihofer, Ann M., Clark D. Hair, and David W. Stepp. "Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 288.1 (2005): R253-R261. In this study both obese Zucker rats (OZR) and lean Zucker rats (LZR) were tested for blood volume to mass ratio for a better understanding of dose responses in obese animals. Following each group of rats was then tested for vascular reactivity (via changes in MAP) to α1 agonists norephinephrine and phenylephrine using body weight as a dose determinant and then plasma volume as a dose determinant. Finally, the study then examined changes in vascular resistance by measuring blood flow in the mesenteric, renal, and hindquarter circulations after the administration of phenylephrine. Previous reports found that OZR are slightly hypertensive compared to LZR, exhibit higher baseline SNA, and have increased pressor responses to ganglionic blockade, which was also the case in this study. Novel to this study however, the Schreihofer group discovered OZR have consistent plasma volumes which then correlate to lower plasma volume/mass ratios. When this idea was then applied to drug administration and doses were determined based upon plasma volume instead of body weight no significant differences in ΔMAP or ΔHR were found following the injections of norepinephrine or phenylephrine. However, after the injection of phenylephrine OZR trended towards increased ΔHR compared to LZR. The study then went on to find that OZR had reduced changes in mesenteric vascular resistance, similar changes in renal resistance, and increased changes in hindquarter resistance when compared to the LZR. These results indicate that changes in vascular reactivity in an OZR compared to LZR are probably not the major cause in the difference in pressor activity following ganglionic blockade. Instead, the authors hypothesize that the difference is probably due to dysfunction in sympathetic control. What this study was able to show was the idea of adrenergic reactivity remodeling in OZR that may contribute to peripheral vascular disease in obese diabetics if the phenomenon presents itself true for humans as well. ~JI