Modulation of blood pressure by dietary potassium and sodium: sex differences and modeling analysis

High Na⁺ intake has been linked to elevations in blood pressure, whereas K⁺ has the opposite effect. The underlying mechanisms involve complex interactions among renal function, fluid volume, fluid-regulatory hormones, vasculature, cardiac function, and the autonomic nervous system. These mechanisms are likely modulated by sex, given the known sex differences in blood pressure regulation and the higher prevalence of hypertension in men. The source of these observed sex differences may be traced to organ and tissue levels, given that kidney function, intrarenal renin-angiotensin system components, renal sympathetic nervous activity, and nitric oxide bioavailability all exhibit sex differences. To assess the functional impact of each of these sex differences, we developed sex-specific computational models to simulate whole-body Na⁺, K⁺, and fluid homeostasis, and the effects on blood pressure. The models describe the interactions among the renal system, cardiovascular system, gastrointestinal system, renal sympathetic nervous system, and renin-angiotensin-aldosterone system. Model simulations suggest that women's attenuated blood pressure response to hypertensive stimuli, including high Na⁺ intake, may be largely attributable to the female renal transporter abundance pattern. In addition, we investigated the causal link between high K⁺ intake and blood pressure reduction. The models simulate renal response to high K⁺ intake, including the immediate gastrointestinal feedforward signals to the kidneys to increase K⁺ excretion, and the longer-term response to decrease proximal fractional Na⁺ reabsorption and distal K⁺ reabsorption. With these assumptions, simulations of high K⁺ intake yielded kaliuresis, natriuresis, and a substantial reduction in blood pressure, even when combined with high Na⁺ intake.<b>NEW & NOTEWORTHY</b> Excessive dietary Na⁺ raises blood pressure, whereas a high K⁺ diet has the opposite effect. The underlying mechanisms are moderated by sex and involve multiple organs and tissues. How do high K⁺-induced alternations in kidney function lower blood pressure, and how do those mechanisms differ between men and women? To answer these questions, we conducted computer simulations to simulate whole-body fluid and electrolyte homeostasis, and the effects of Na⁺ and K⁺ intake on blood pressure.