Obesity-induced increases in sympathetic nerve activity: sex matters

Abstract

Abundant evidence obtained largely from male human and animal subjects indicates that obesity increases sympathetic nerve activity (SNA), which contributes to hypertension development. However, recent studies that included women reported that the strong relationships between muscle SNA and waist circumference or body mass index (BMI) found in men are not present in overweight and obese women. A similar sex difference in the association between adiposity and hypertension development has been identified in animal models of obesity. In this brief review, we consider two possible mechanisms for this sex difference. First, visceral adiposity, leptin, insulin, and angiotensin II have been identified as potential culprits in obesity-induced sympathoexcitation in males. We explore if these factors wield the same impact in females. Second, we consider if sex differences in vascular reactivity to sympathetic activation contribute. Our survey of the literature suggests that premenopausal females may be able to resist obesity-induced sympathoexcitation and hypertension in part due to differences in adipose disposition as well as its muted inflammatory response and reduced production of pressor versus depressor components of the renin-angiotensin system. In addition, vascular responsiveness to increased SNA may be reduced. However, more importantly, we identify the urgent need for further study, not only of sex differences per se, but also of the mechanisms that may mediate these differences. This information is required not only to refine treatment options for obese premenopausal women but also to potentially reveal new therapeutic avenues in obese men and women.

Keywords: Blood pressure; Insulin; Leptin; Sex differences; Vasoconstriction; Visceral obesity.

Figure 1. MSNA does not correlate with adiposity in women

Linear regression analysis demonstrating lack of relationship between resting MSNA and waist-hip ratio (Panel A) and BMI (Panel B) in healthy premenopausal women (n=23, age: 35±3 yrs). Retrospective data analysis of microneurographic recordings from Fadel laboratory.

Figure 2. Comparison of leptin’s effects in male and female rats

A, ICV leptin increased MAP in male rats (n=16), but not in female rats during diestrus (n=15) or proestrus (n=14). B, The basal HR of male rats is lower than that of female rats. ICV leptin increased HR in both male (n=16) and female rats (n=15, diestrus; n=14, proestrus). C, ICV leptin increased LSNA in male rats (n=5) and female proestrus rats (n=6), but not in females in diestrus (n=6); D, ICV leptin increased RSNA in male rats (n=5) and females in proestrus (n=4), but not in females in diestrus (n=4). E, ICV leptin increased splanchnic SNA (SSNA) in male rats (n=6) and female rats (n=5, diestrus; n=4,proestrus). * P < 0.05 vs control ; † P < 0.05 between groups. Data from (Shi & Brooks, 2014).

Figure 3. Leptin increases LSNA and HR in E2-treated ovariectomized (OVX) rats, but not in OVX rats

A, ICV leptin did not alter MAP in OVX rats (n=5) or in E2-treated OVX rats (OVX-E2, n=4). However, ICV leptin increased HR (B) and LSNA (C) in E2-treated OVX rats (n=4), but not in OVX rats (n = 5). * P< 0.05 vs control; † P < 0.05 between groups. Data from (Shi & Brooks, 2014)

Figure 4. Comparison of insulin’s effects on MAP, LSNA and HR in male and female rats

A, ICV insulin increased MAP in male rats (n=5), but not in female rats in proestrus (n=5) and diestrus (n=5). However, ICV insulin increased HR (B) and LSNA (C) similarly in male (n=5), female proestrus (n=5) and diestrus rats (n=5). * P < 0.05 vs control. Data from (Shi & Brooks, 2014).

Figure 5. Summary

General schematic depicting some factors that may explain the lesser propensity for obese females (B) to exhibit elevated SNA and AP compared to obese males (A). In females, potential inhibitory and facilitatory effects of 17β-estradiol (E2) are indicated by minus (−) and plus (+) symbols, respectively. See text for details.