Sympathetic modulation of baseline hindlimb blood flow and vascular conductance in a model of prediabetes using young Zucker Diabetic Fatty rats

Although associated with vascular disease, few studies have addressed the impact of prediabetes on vascular function. Thus, we sought to identify differences in baseline sympathetic vascular control between male Zucker (pre)Diabetic Fatty rats (PD) and lean controls (CTL) (n = 11/group). Hindlimb blood flow (Q h ) and vascular conductance (VC) were assessed under local infusion of BIBP3226 (NPY Y 1 ‐receptor (Y1R) antagonist), prazosin (α 1 ‐receptor antagonist) and dual blockade. With no differences in baseline, BIBP3226 increased Q h 0.3 ± 0.1 ml/min in both groups and VC increased 4.2 ± 0.9 and 4.5 ± 1.1 μl/min/mmHg in PD and CTL respectively (P < 0.05). Prazosin increased Q h 0.2 ± 0.04 and 0.2 ± 0.1 ml/min and VC increased 3.3 ± 0.5 and 4.2 ± 1.0 μl/min/mmHg in PD and CTL respectively (P < 0.05). Dual blockade increased Q h 0.2 ± 0.05 ml/min in both groups and VC increased 4.6 ± 1.2 and 4.4 ± 0.72 μl/min/mmHg in PD and CTL respectively (P < 0.05). Recovery time from maximum after drug infusion to 37% of baseline (1/e) for Q h and VC was shorter in PD vs. CTL (% of CTL, Q h and VC respectively: BIBP3226 68% and 53%, Prazosin 75% and 81%, dual blockade 78% and 70%) (P < 0.05). In support, red and white vastus muscle Y1R, α1R, and tyrosine hydroxylase expression was higher in PD vs. CTL (P < 0.05). These data suggest that the SNS is upregulated in prediabetes leading to persisting effects on skeletal muscle blood flow. NSERC and NIH.