High salt diet increases the pressor response to stress in female, but not male ETB-receptor-deficient rats

Abstract

Acute stress in both rodents and humans causes a transient rise in blood pressure associated with an increase in plasma endothelin-1 (ET-1). High salt (HS) intake also increases ET-1 production, and interestingly, blunts the pressor response to acute air jet stress in rats. We previously reported that female rats lacking functional ETB receptors everywhere except sympathetic nerves (ETB def) had a greater degree of hypertension in response to a HS diet compared to their male counterparts when measured by the tail cuff method. However, we now report that salt-induced hypertension is not different between sexes when measured by telemetry. Therefore, additional experiments were designed to test the hypothesis that female ETB def rats are more sensitive to acute stress when on a HS diet. The pressor response, measured by telemetry, to acute air jet stress was similar between male transgenic control (Tg control) and ETB def rats following chronic HS intake. In contrast, female ETB def rats had a significantly greater pressor response (about twofold higher) than female or male Tg control or male ETB def rats maintained on HS, a finding that cannot be explained by increased vascular reactivity to ET-1 in female rats as we observed that male ETB def rats had a greater pressor response to i.v. infusion of ET-1 compared to females. Furthermore, HS feeding exacerbated the pressor response to ET-1 in both male and female ETB def rats. Given our previous studies demonstrating that the ETA receptor functions to reduce the pressor response to acute stress, these findings further support a role for the ET receptor system in the pressor response to acute stress and that female rats have reduced ETA receptor activity when on a HS diet compared to males.

Keywords: Blood pressure; Endothelin‐1; Stress.

Figure 1

Comparison of blood pressure in male and female ET_B def rats. (A) Systolic blood pressure measured by tail cuff in male (n = 7) and female (n = 9) ET_B def rats before and after 2 weeks of HS feeding. (B) 12 h mean arterial pressure (MAP) in male (n = 7) and female (n = 9) ET_B def rats before and after 4 weeks of HS feeding. Data expressed as mean ± SE. *P < 0.05versus male.

Figure 2

Total mean arterial pressure response to acute air jet stress expressed as area under the curve (AUC) in Tg control and ET_B def, male and female rats maintained on (A) NS diet (n = 5–6) and (B) HS diet (n = 5–6). Data expressed as mean ± SE; *P < 0.05 versus male Tg control; ^†P < 0.05 versus female Tg control.

Figure 3

Comparison of MAP in response to intravenous bolus of increasing doses of ET-1 (0.1, 0.3, and 1.0 nmol/kg). Panels (A and C) represent MAP tracings from male and female (n = 3–5) ET_B def rats maintained on NS or HS diet, respectively, for 3 weeks. (B and D) represent the AUC after ET-1 infusion calculated from the baseline. Data expressed as means ± SE.

Figure 4

Comparison of MAP in response to increasing doses of S6c (ET_B agonist) in male and female ET_B def rats on NS diet. Data expressed as means ± SE.