Minson, Christopher T.

Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. Although ≈80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine whether women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared with women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (aged 18–35 years) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53; 25±4 years) and women with natural menstrual cycles (n=74; 25±4 years). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure, 89±1 versus 85±1 mm Hg, respectively; P =0.01), although MSNA was similar in both groups (MSNA burst incidence, 16±1 versus 18±1 bursts/100 heartbeats, respectively; P =0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 versus 4.7±0.2 L/min, respectively; P =0.47) and total peripheral resistance (19.2±0.8 versus 20.0±0.9 U, respectively; P =0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use when compared with naturally menstruating women in the early follicular phase.

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia ( n = 8), 6 h when glucose was clamped at ∼7 mmol/l ( n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose ∼11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance ( n = 10). Insulin concentrations in all instances were maintained at ∼65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.

We tested the hypothesis that acute hypoxia would alter the sensitivity of arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20–33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity by using the modified Oxford technique during both normoxia and hypoxia (12% O2). Compared with normoxia, hypoxia reduced arterial O2 saturation levels from 96.8 ± 0.3 to 80.7 ± 1.4% ( P < 0.001), increased heart rate from 59.8 ± 2.4 to 79.4 ± 2.9 beats/min ( P < 0.001), increased mean arterial pressure from 96.7 ± 2.5 to 105.0 ± 3.3 mmHg ( P = 0.002), and increased sympathetic activity 126 ± 58% ( P < 0.05). The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by hypoxia (heart rate: −1.02 ± 0.09 vs. −1.02 ± 0.11 beats · min−1 · mmHg−1; nerve activity: −5.6 ± 0.9 vs. −6.2 ± 0.9 integrated activity · beat−1 · mmHg−1; both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity.

The influence of the ovarian cycle on muscle sympathetic nerve activity (MSNA) remains controversial. Some studies report an increase of resting MSNA during the mid luteal (ML) phase of the ovarian cycle compared with the early follicular phase, whereas other studies do not. These inconsistent findings may be attributable, in part, to the variable surges in estradiol and progesterone. We tested the hypothesis that the degree of sympathoexcitation during the ML phase (ΔMSNA) is associated with changes in estradiol (ΔE 2 ) and progesterone (ΔP). Multiple regression analysis of data from previous studies with complete recordings of mean arterial pressure, MSNA, E 2 , and P during both early follicular and ML phases were available from 30 eumenorrheic women (age, 28±1 years; body mass index, 23±0 kg/m 2 ). ML phase increased E 2 (37±2 to 117±9 pg/mL; P <0.001), P (1±0 to 11±1 ng/mL; P <0.001), and MSNA (12±1 to 15±1 bursts/min; P =0.02), but did not alter mean arterial pressure (83±2 to 83±2 mm Hg; P =0.91). ΔMSNA was correlated with ΔE 2 ( r =−0.50, P =0.003) and ΔE 2 /ΔP ( r =−0.52, P =0.002) but not ΔP ( r =0.21, P =0.13). There was no association between Δmean arterial pressure and ΔE 2 ( r =−0.13, P =0.49), ΔP ( r =−0.04, P =0.83), or ΔE 2 /ΔP ( r <0.01, P =0.98). In conclusion, sympathoexcitation during the ML phase of the ovarian cycle seems to be dependent, in part, on the degree of sex steroid surges. This dynamic interaction among E 2 , P, and MSNA likely explains previously reported inconsistencies in the field; it remains possible that other sex steroids, such as testosterone, might explain further variance.

Background —We tested sympathetic and cardiovagal baroreflex sensitivity during the placebo or “low-hormone” phase (LH) and 2 to 3 weeks later during the “high-hormone” phase (HH) of oral contraceptive (OC) use in 9 women. Methods and Results —Sympathetic baroreflex sensitivity was assessed by intravenous doses of sodium nitroprusside and phenylephrine and defined as the slope relating muscle sympathetic nerve activity (by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. No difference was observed for resting muscle sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic baroreflex sensitivity was greater and mean arterial pressure was higher during the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was greater in the LH than in the HH phase. Conclusions —Sympathetic and cardiovagal baroreflex sensitivities change during the 28-day course of OC use. Furthermore, changes in baroreflex sensitivity with OC differ from changes in baroreflex sensitivity during the normal menstrual cycle.

Background —Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. Methods and Results —Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170±151 U/min; ML, 2252±251 U/min; P <0.001) and plasma norepinephrine levels (EF, 240±21 pg/mL; ML, 294±25 pg/mL; P =0.025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, −4.15; FL, −5.42; P =0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. Conclusions —The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.