Figure 7.

hKLK1 promoted cGMP production and inhibited Ca²⁺ concentration in CSMC by the PI3K/AKT/eNOS pathway under physiological condition. The diagram of the coculture system of CSMC and EC is shown in panel (a). Panels (b) and (c) show the cGMP and intracellular Ca²⁺ level changes at the administration of LMWK, HOE140, LY294002, and L-NAME in both CSMC from WTR and TGR. All images were captured at magnification of 200x. Panel (d) shows the potential signaling pathway downstream to hKLK1 involved in normal CSMC relaxation. Each bar represents mean ± standard error of the mean. ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001. hKLK1: human tissue kallikrein 1; NO: nitric oxide; cGMP: cyclic guanosine monophosphate; CSMC: cavernous smooth muscle cell; EC: endothelial cells; WTR: wild-type rats; TGR: transgenic rats; WTDM: diabetic wild-type rats; TGDM: diabetic transgenic rats; TGDMH: diabetic transgenic rats administrated with HOE140.