Endothelial dysfunction and hypercontractility of vascular myocytes are ameliorated by fluvastatin in obese Zucker rats

Static exercise causes activation of the sympathetic nervous system, which results in increased blood pressure (BP) and renal vascular resistance (RVR). The question arises as to whether renal vasoconstriction that occurs during static exercise is due to sympathetic activation and/or related to a pressure-dependent renal autoregulatory mechanism. To address this issue, we monitored renal blood flow velocity (RBV) responses to two different handgrip (HG) exercise paradigms in 7 kidney transplant recipients (RTX) and 11 age-matched healthy control subjects. Transplanted kidneys are functionally denervated. Beat-by-beat analyses of changes in RBV (observed via duplex ultrasound), BP, and heart rate were performed during HG exercise in all subjects. An index of RVR was calculated as BP/RBV. In protocol 1, fatiguing HG exercise (40% of maximum voluntary contraction) led to significant increases in RVR in both groups. However, at the end of exercise, RVR was more than fourfold higher in control subjects than in the RTX group (88 vs. 20% increase over baseline; interaction, P < 0.001). In protocol 2, short bouts of HG exercise (15 s) led to significant increases in RVR at higher workloads (50 and 70% of maximum voluntary contraction) in the control subjects (P < 0.001). RVR did not increase in the RTX group. In conclusion, we observed grossly attenuated renal vasoconstrictor responses to exercise in RTX subjects, in whom transplanted kidneys were considered functionally denervated. Our results suggest that renal vasoconstrictor responses to exercise in conscious humans are mainly dependent on activation of a neural mechanism.