Altered baroreflex sensitivity in young women with a family history of hypertension.

A positive family history of hypertension (+FH) is a risk factor for the future development of hypertension. Hypertension is associated with reductions in baroreflex sensitivity (BRS). Therefore, we hypothesized that young women with a +FH [ n = 12, 22 ± 1 yr, body mass index (BMI) 21 ± 1 kg/m2, mean arterial pressure (MAP) 79 ± 1 mmHg] would have lower BRS compared with young women without a family history of hypertension (-FH) ( n = 13, 22 ± 1 yr, BMI 21 ± 1 kg/m2, MAP 77 ± 2 mmHg, all P > 0.05 between groups). Continuous measurements of muscle sympathetic nerve activity, blood pressure, and electrocardiogram derived R-R interval were recorded at rest and during a Valsalva maneuver. Both cardiovagal BRS and vascular sympathetic BRS were assessed. Resting cardiovagal BRS was reduced in the +FH women (all sequences: -FH 32.3 ± 3.7 vs. +FH 20.2 ± 2.9 ms/mmHg, P = 0.02). Cardiovagal BRS during phase IV (-FH 16.5 ± 2.7 vs. +FH 7.6 ± 1.3 ms/mmHg, P < 0.01) but not phase II (-FH 5.5 ± 0.9 vs. +FH 5.0 ± 0.8 ms/mmHg, P = 0.67) of the Valsalva maneuver was also lower in the +FH women. Vascular sympathetic BRS at rest (-FH -2.38 ± 0.7 vs. +FH -2.33 ± 0.3 bursts· min-1·mmHg-1, P = 0.58) and during the Valsalva (-FH -0.74 ± 0.23 vs. +FH -0.66 ± 0.18 bursts·15 s-1·mmHg-1, P = 0.79) were not different between groups. These data suggest that healthy young women with a positive family history of hypertension have reduced cardiovagal BRS. This may be one mechanism contributing to the increased incidence of hypertension in this population later in life. NEW & NOTEWORTHY Having a family history of hypertension increases the risk of developing future hypertension. Reductions in baroreflex function have been demonstrated in hypertension and are an important marker for future cardiovascular disease. We show that young women with a family history of hypertension have lower cardiovagal baroreflex sensitivity. This alteration in autonomic function may be one mechanism contributing to the future incidence of hypertension in this patient population.

Ovarian hormones modulate endothelin-1 receptor responses in young women.

OBJECTIVE: We recently demonstrated ETBR mediate vasodilation in young but not postmenopausal women; it is unclear if this is related to age or a decline in ovarian hormones. The purpose of this study was to test the hypothesis that ETBR responses are modulated by ovarian hormones. METHODS: We measured cutaneous vasodilatory responses in 12 young women (22 ± 1 years, 23 ± 1 kg/m2 ) during the ML (days 20-25) and EF (days 2-5) phases of the menstrual cycle. Cutaneous microdialysis perfusions of lactated Ringer (control), ETBR antagonist (BQ-788, 300 nmol/L), and ETAR antagonist (BQ-123, 500 nmol/L) were performed, followed by local heating to 42°C. RESULTS: Serum estradiol (ML: 118 ± 16 vs EF: 44 ± 9 pg/mL, P < 0.05) and progesterone (ML: 8.3 ± 1.0 vs EF: 0.7 ± 0.2 ng/mL, P < 0.05) were higher during ML vs EF phase. ETBR blockade decreased vasodilation during ML (control: 91 ± 2 vs BQ-788: 83 ± 2%CVCmax, P < 0.05) but not EF (control: 89 ± 2 vs BQ-788: 89 ± 1%CVCmax). ETAR blockade also decreased vasodilation during ML (control: 91 ± 2 vs BQ-123: 87 ± 2%CVCmax, P < 0.05) but not EF (control: 89 ± 2 vs BQ-123: 92 ± 2%CVCmax). CONCLUSIONS: These data suggest that fluctuations in ovarian hormones modulate ETBR and ETAR responses in young women.

ETB receptor contribution to vascular dysfunction in postmenopausal women.

Endothelin-1 (ET-1) contributes to age-related endothelial dysfunction in men via the ETA receptor. However, there are sex differences in the ET-1 system, and ETB receptors are modulated by sex hormones. The purpose of this study was to test the hypothesis that ETB receptors contribute to impaired vasodilatory function in postmenopausal women (PMW). We measured flow-mediated dilation (FMD) using ultrasound, and cutaneous nitric oxide-mediated vasodilation during local heating (42°C) via laser Doppler flowmetry in 18 young women (YW; 22 ± 1 yr) and 16 PMW (56 ± 1 yr). Cutaneous microdialysis perfusions of lactated Ringer (control), an ETB receptor antagonist (BQ-788, 300 nM), and an ETA receptor antagonist (BQ-123, 500 nM), were done through separate fibers, followed by perfusions of sodium nitroprusside (28 mM) and local heating to 43°C (max). Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial pressure and expressed as a percent of maximal dilation. FMD (YW: 7.5 ± 0.5 vs. PMW: 5.6 ± 0.6%) and cutaneous vasodilation (YW: 93 ± 2 vs. PMW: 83 ± 4%CVCmax) were lower in PMW (both P < 0.05). Blockade of ETB receptors decreased cutaneous vasodilation in YW (87 ± 2%CVCmax; P < 0.05 vs. control) but increased vasodilation in PMW (93 ± 1%CVCmax; P < 0.05 vs. control). ETA receptor blockade had minimal effect in YW (92 ± 1%CVCmax) but increased cutaneous vasodilation in PMW (91 ± 2%CVCmax; P < 0.05 vs. control). In conclusion, ETB receptors mediate vasodilation in YW, but this effect is lost after menopause. Impaired vasodilatory function in PMW is due in part to a loss of ETB-mediated dilation.