Altered phenylephrine (PE)‐induced vascular contractility and reduced endothelial function during the onset of renal wrap hypertension

The rat one‐kidney, figure‐8 renal wrap model of hypertension is salt‐sensitive, Ang II dependent and closely mimics human glomerulosclersis. Moreover, there is increased sympathetic nervous system function in this model of hypertension. However, a dearth of information on vascular changes associated with this model exists. We hypothesized that similar to other hypertension models there would be enhanced PE‐induced contraction and reduced acetylcholine (ACh) –mediated relaxation, indicating endothelial dysfunction. 7 days post‐surgery male Sprague Dawley wrap rats had significantly greater blood pressure compared to sham rats (106 + 3 vs. 133 + 5 mm Hg; p<0.05). Using a DMT myograph for contractility measures, we observed in the aortic rings a significant decrease in maximal contractile response to PE (143 + 8 % vs. 109 + 12 % KCl contraction; p<0.05). In addition, there was significant endothelial dysfunction indicated by impairment to ACh‐induced relaxation (100% vs.70% of initial PE contraction; p<0.05). Lastly, immunohistochemistry of thoracic aorta revealed significant increases in actin stress fibers and apoptosis, indicated by nuclear fragmentation in endothelium from wrap as compared to sham rats. In conclusion, in the thoracic aorta there are significant vascular changes which potentially contribute to the development of hypertension. Funded by: NIH R00HL087927 (CAN) and R00HL91177 (ABB).