IgA nephropathy with early kidney disease is associated with increased arterial stiffness and renin-angiotensin system activity.

BACKGROUND: IgA nephropathy is associated with increased cardiovascular risk, though whether this is due to loss of kidney function or proteinuria is unclear. METHODS: For this study 10 normotensive IgA nephropathy subjects with early kidney disease (41±5 yrs, glomerular filtration rate (GFR) 87±9 ml/min, proteinuria 720±300 mg/d) and 10 gender- and blood pressure-matched healthy controls (36±1 yrs, estimated GFR 102±5 ml/min, proteinuria 70±6 mg/d) were studied in high-salt balance. Blood pressure and arterial stiffness, expressed as pulse wave velocity and aortic augmentation index, were measured at baseline and in response to 60 min of angiotensin II (AngII) infusion. RESULTS: At baseline, IgA nephropathy subjects demonstrated similar pulse wave velocity (8.6±0.7 vs. 8.0±0.4 m/s, p=0.5) but increased aortic augmentation index (12.6±3.1 vs. 1.8±4%, p=0.04) and a trend towards increased circulating renin-angiotensin system (RAS) components (plasma renin activity, 0.55±0.18 vs. 0.21±0.05 ng/l/s, p=0.08; angiotensin II, 25±5 vs. 16±1 ng/l, p=0.08) compared with controls. However, despite similar baseline blood pressure values (p=0.8), IgA nephropathy was associated with reduced arterial sensitivity to AngII challenge (Δmean arterial pressure: 19±4 vs. 29±1 mm Hg, p=0.05; Δpulse wave velocity: -0.06±0.6 vs. 1.5±0.3 m/s, p=0.07) compared with controls, even after multivariate analysis. CONCLUSION: Even in the setting of early kidney disease, IgA nephropathy is associated with increased arterial stiffness and decreased angiotensin II responsiveness, a marker of increased RAS activity.

Sex influences the effect of body mass index on the vascular response to angiotensin II in humans.

OBJECTIVE: Sex influences the cardiorenal risk associated with body mass index (BMI). The role of the renin-angiotensin-aldosterone system in adiposity-mediated cardiorenal risk profiles in healthy, non-obese men and women was investigated. METHODS: Systemic and renal hemodynamic responses to angiotensin-II (AngII) as a function of BMI, waist and hip circumference, waist-hip ratio, as well as fat and lean mass were measured in 18 men and 25 women in high-salt balance, stratified by BMI (<25 kg/m2 (ideal body weight (IBW)) vs. ≥25 kg/m2 overweight)). RESULTS: In men (n = 7, BMI 23 ± 1 kg/m2) and women (n = 14, BMI 22 ± 2 kg/m2) of IBW, BMI was not associated with the systolic blood pressure (SBP) response to AngII. In contrast, overweight men (n = 11, 29 ± 2 kg/m2) demonstrated a progressively more blunted vasoconstrictor SBP response to AngII challenge as BMI increased (P = 0.007), even after adjustment for covariates. Women maintained the same relationship between BMI and the SBP response to AngII irrespective of weight status (P = 0.2, IBW vs. overweight women). Compared to BMI, other adiposity measures showed similar associations to systemic AngII responsiveness in men but not in women. Increasing BMI was associated with a blunted renovasoconstrictor response to AngII in all subjects, but was more pronounced in men. CONCLUSION: Sex influences the effect of adiposity on vascular angiotensin-responsiveness.

Impact of gender on the cardiac autonomic response to angiotensin II in healthy humans.

Premenopausal women have a lower risk of cardiovascular disease (CVD) compared with men of a similar age. Furthermore, the regulation of factors that influence CVD appears to differ between the sexes, including control of the autonomic nervous system (ANS) and the renin-angiotensin system. We examined the cardiac ANS response to angiotensin II (Ang II) challenge in healthy subjects to determine whether differences in women and men exist. Thirty-six healthy subjects (21 women, 15 men, age 38 ± 2 years) were studied in a high-salt balance. Heart-rate variability (HRV) was calculated by spectral power analysis [low-frequency (LF) sympathetic modulation, high-frequency (HF) parasympathetic/vagal modulation, and LF:HF as a measure of overall ANS balance]. HRV was assessed at baseline and in response to graded Ang II infusions (3 ng·kg(-1)·min(-1) × 30 min; 6 ng·kg(-1)·min(-1) × 30 min). Cardiac ANS tone did not change significantly in women after each Ang II dose [3 ng·kg(-1)·min(-1) mean change (Δ)LF:HF (mean ± SE) 0.5 ± 0.3, P = 0.8, vs. baseline; 6 ng·kg(-1)·min(-1) ΔLF:HF (mean ± SE) 0.5 ± 0.4, P = 0.4, vs. baseline], whereas men exhibited an unfavorable shift in overall cardiac ANS activity in response to Ang II (ΔLF:HF 2.6 ± 0.2, P = 0.01, vs. baseline; P = 0.02 vs. female response). This imbalance in sympathovagal tone appeared to be largely driven by a withdrawal in cardioprotective vagal activity in response to Ang II challenge [ΔHF normalized units (nu), -5.8 ± 2.9, P = 0.01, vs. baseline; P = 0.006 vs. women] rather than an increase in sympathetic activity (ΔLF nu, -4.5 ± 5.7, P = 0.3, vs. baseline; P = 0.5 vs. women). Premenopausal women maintain cardiac ANS tone in response to Ang II challenge, whereas similarly aged men exhibit an unfavorable shift in cardiovagal activity. Understanding the role of gender in ANS modulation may help guide risk-reduction strategies in high-risk CVD populations.