Lisinopril augments the combined effect of nitric oxide and potassium channels on endothelium‐dependent relaxation in spontaneously hypertensive rats

Abstract

Endothelium‐dependent relaxation is reported to be impaired in hypertension. However, there is equivocal evidence on the exact nature of the underlying dysfunction and whether it could be affected by antihypertensive drugs specifically angiotensin‐converting enzyme inhibitors. This study was conducted to evaluate the contribution of NO and potassium channels to endothelial function after lisinopril treatment in spontaneously hypertensive rats. Male animals (10–12 weeks old) were treated with lisinopril (20mg/Kg/day) for 10 weeks. ACh (0.1 nM–10μM)‐induced relaxation of third order mesenteric arteries was measured on a wire myograph with isometric recording in the presence and absence of different blockers. In the presence of inhibitor of nitric oxide synthase (LNMMA 100uM), the maximum relaxation of arteries from untreated (UT) and treated (T) rats to ACh was reduced by 19±3.5% and 5.0±01.6% respectively, while in the presence of SK and IK channel blockers (apamin 100nM and TRAM‐34 10μM) it was reduced by 35±3.5% and 34%±6.25%; respectively (n=10–22). With combined blockade, ACh‐induced relaxation was inhibited by 29±6.2% UT and 65±3.2 % T. Our results suggest that chronic treatment with lisinopril, although it reduced the relative contribution of nitric oxide alone it enhanced the combined effect of nitric oxide and potassium channels towards more endothelium‐dependent relaxation.