Sex-Specific Differences in the Pathophysiology of Hypertension

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Metabolic Disease Research

Background:

• Hypertension is a common comorbidity in cardiometabolic diseases, affecting nearly one-third of adults.
• Established mechanisms include pressure natriuresis, the renin-angiotensin system (RAS), sympathetic nervous system activity, oxidative stress, and endothelial dysfunction.
• Significant sex-based differences in hypertension development exist, but underlying pathophysiological mechanisms remain incompletely understood.

Purpose of the Study:

• To review and postulate the role of sexually dimorphic fat metabolism in the physiology of hypertension.
• To elucidate how sex hormones, particularly estrogen and androgens, influence adipose tissue distribution and function in relation to hypertension.
• To highlight potential sex-specific therapeutic targets for hypertension management.

Main Methods:

• This is a review article, synthesizing existing literature on hypertension, sex hormones, and fat metabolism.
• The review focuses on the contrasting effects of estrogen and androgens on adipose tissue deposition (subcutaneous vs. visceral) and function.
• Pathophysiological pathways linking fat metabolism to hypertension, including inflammation and RAS activation, are discussed.

Main Results:

• Estrogen promotes subcutaneous fat deposition and adaptive hyperplasia, leading to anti-inflammatory effects, inhibition of metabolic dysfunction-associated fatty liver disease (MAFLD), and reduced RAS activation, contributing to lower hypertension rates in pre-menopausal females.
• Androgens and estrogen deficiency promote visceral and ectopic fat deposition (including hepatic), increasing pro-inflammatory cytokines and potentially activating the RAS, thereby contributing to hypertension development in males and post-menopausal females.
• Sexually dimorphic fat metabolism represents a critical, yet understudied, factor in hypertension pathogenesis.

Conclusions:

• Sex-specific differences in fat metabolism, driven by sex hormones, significantly contribute to the varying prevalence and mechanisms of hypertension between males and females.
• Targeting sex-specific fat metabolism pathways may offer novel strategies for personalized hypertension prevention and treatment.
• Further research into these sex-specific mechanisms is crucial for developing comprehensive, tailored cardiovascular care.