Sex-specific dichotomy of chronic mild stress effects on blood pressure and longitudinal measurements of renal sympathetic nerve activity: are females really protected?
This study indicates that chronic mild stress affects blood pressure and renal nerve activity differently in male and female rats, with potential implications for understanding hypertension mechanisms.
Where it sits
this study against the rest of the vasopressin corpusSummary and findings
This study investigated the effects of chronic mild stress on blood pressure and renal sympathetic nerve activity in male and female rats. Male CMS rats exhibited similar blood pressure levels after ablation of renal nerves, while female CMS rats showed increased renal sympathetic nerve activity despite normal blood pressure. The study highlights potential sex-specific differences in the regulation of blood pressure and renal nerve activity.
Abstract
Modulation of renal nerves to improve blood pressure (BP) control has become a topic of intense investigation over the last 10-15 years. Given that renal innervation is composed of mixed nerve fibers containing both afferent (sensory) and efferent (sympathetic) fibers, subsequent preclinical studies have been investigating their respective roles in hypertension pathobiology in different genetic and salt-sensitive rat models. Here we set out to investigate how renal afferent and efferent nerves regulate hypertension development in the chronic mild stress model (CMS). We show that in male CMS rats, ablation of afferent renal nerves (ARDNx) and all renal nerves (TRDNx) resulted in similar BP (104 +/- 2 mmHg vs. 101 +/- 3 mmHg, respectively), both reduced compared to the SHAM group (118 +/- 1 mmHg, p = 0.003 and p < 0.001, respectively) arguing for a prominent role of afferent renal nerves in CMS hypertension. Additionally, we show a reduction of vasopressin (AVP) V1b but not V1a receptor abundance in ARDNx CMS males but not females, suggesting that afferent renal nerves are involved in increase in BP via V1b AVP receptor. We additionally show that despite normal BP, female CMS rats display increased renal sympathetic nerve activity (RSNA; 2.39 +/- 0.23 bursts/beat vs. 1.44 +/- 0.12 bursts/beat, p < 0.005) measured directly with implanted telemetry in conscious rats over one week and aortic stiffness, as evidenced by increased aortic pulse wave velocity (173.2 +/- 50.9 mm/s vs. - 10.7 +/- 54.6 mm/s in controls, p = 0.0393).