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1 Integrated Physiology, University Colorado, United States
2 Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado, United States
3 Medicine, West Virginia University, Morgantown, West Virginia, United States
4 Department of Health and Kinesiology, Texas A and M University, College Station, Texas, United States
5 Department of Biomedical Sciences, University of Missoouri, Columbia, Missouri, United States
6 Medicine, The Milton S. Hershey Medical Ctr, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States
7 Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: mdelp{at}ufl.edu.
Approximately 40% of patients with type 2 diabetes present with concurrent hypertension at the time of diabetes diagnosis. As blood flow distribution and peripheral vascular resistance are determined primarily at the level of the microvasculature, enhanced vasoconstrictor capacity could have profound implications on the development of hypertension and the progression of insulin resistance to overt diabetes. The purpose of this study was to determine whether enhanced skeletal muscle vasoconstrictor responsiveness precedes the development of diabetes and hypertension. Male Zucker diabetic fatty (ZDF) rats were studied at 7, 13 and 20 weeks of age to represent prediabetic, acute and chronic diabetic states, respectively. Conscious mean arterial pressure (MAP), fasted plasma insulin and glucose, and vasoconstrictor reactivity of isolated soleus and gastrocnemius muscle 1A arterioles were measured in fatty and age-matched lean control rats. Elevated MAP was manifest in acute diabetes (Lean, 117 ± 1; Fatty 135 ± 3 mmHg) and persisted with chronic diabetes (Lean, 113 ± 2; Fatty 135 ± 3 mmHg). This higher MAP was preceded by augmented vasoconstrictor reactivity to norepinephrine and endothelin-1 in gastrocnemius muscle arterioles in the prediabetic state that is later accompanied by diminished 
-adrenergic vasodilation and enhanced myogenic vasoconstriction in overt diabetes. Collectively, these results indicate that vasoconstrictor dysfunction in skeletal muscle arterioles precedes the development of diabetes and hypertension in ZDF rats.
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