This study investigated whether there are sex differences in vasorelaxation through the nitric oxide (NO)/soluble guanylate cyclase (sGC) pathway. The hearts of female (F) and castrated male (CM) pigs (6-month-old) were collected at a local abattoir, and left anterior descending coronary arteries were isolated to perform organ chamber experiments. Vasorelaxant activity was assessed based on the pD₂ values. Bradykinin induced a concentration-dependent relaxation, which was comparable between F [8.55±0.13] and CM [8.67±0.11]. In the presence of L-NAME (100 μM, NO synthase inhibitor), the response to bradykinin was attenuated similarly in F [7.27±0.24] and CM [7.42±0.29]. Sodium nitroprusside (SNP, reduced sGC agonist) also induced relaxation in a concentration-dependent manner, and the potency in F [6.54±0.12] was similar to that in CM [6.50±0.11]. Pretreatment with ODQ (10 μM, sGC heme oxidant) attenuated SNP-induced relaxation similarly in F [4.77±0.19] and CM [4.78±0.09]. Likewise, there were no differences in BAY 60-2770 (oxidized/apo sGC agonist)-induced relaxation irrespective of the presence [10.64±0.20 (F) vs. 10.47±0.14 (CM)] or absence [9.89±0.11 (F) vs. 9.67±0.15 (CM)] of ODQ. These findings suggest that there are no differences in the regulation of coronary artery tone in response to sGC agonists between F and CM.