The study heavily relies on computational models, which, while useful for exploring complex interactions, are limited by the accuracy of their underlying assumptions and parameterizations. The models were parameterized based on rat data and extrapolated to humans due to insufficient human data, introducing potential species-specific differences and limiting the reliability of the human-related predictions. The simplification of complex systems, such as the RAAS and the absence of explicit representation of factors like NO and superoxide, further restricts the models' ability to fully capture the nuanced interplay of physiological processes.

Although the study explores sex differences in blood pressure regulation, it focuses on premenopausal women, excluding postmenopausal women and thus providing an incomplete understanding of sex-related influences on blood pressure. The models also do not account for the effects of medication which is significant as women's treatment response to hypertension is different from men's.

The models do not account for other important factors known to influence blood pressure, such as age, lifestyle (e.g., physical activity, diet beyond Na+ and K+ intake), genetics, and other medical conditions. These omissions limit the models' applicability to real-world scenarios where these factors play significant roles.