Abstract In order to improve the intraoperative applications, this paper presents the advantages of using Guyton's model in hypotensive control system development. In this system, the mean arterial pressure is decreased and maintained at a low level during anaesthesia by controlling sodium nitroprusside infusion rate. The key of the study is to develop a physiological model of cardiovascular dynamics to present the mean arterial pressure response to sodium nitroprusside, which was considered as a linear model in most of known blood pressure control systems. Being linear, the previous models cannot accurately mimic a physiological system of human circulation, especially at deep hypotensive control with strong reaction of the body. The enhanced model in this study was modified based on Guyton's model of human circulation. It is useful to design a PID controller, which allows studying and handling the wide range of the body sensitivities. This model is also helpful for studying the behaviors of patients under anaesthesia conditions, such as the perfusion of organs and the reaction of the body at hypotensive state. A fuzzy gain scheduler and a supervising algorithm were also developed for online tuning the controller to handle the behavior of the body. The control system was tested on 25 experiments on seven pigs in the animal laboratory. Simulation and experiment results proved the usefulness of Guyton's model in control system design which can present the dynamical response of blood pressure in the circulation under and after hypotensive control. The results also indicated the safety and stability of the controller.