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Hypoglycemia impacts baroreflex control of blood pressure and cardio-vagal tone. The carotid bodies are sensitive to low glucose and mediate hypoglycemic counterregulation. Peripheral chemoreceptors in the carotid body also regulate respiration, sympathetic outflow, and blood pressure by serving as multi-modal physiological sensors. We hypothesized that desensitization of the carotid bodies by hyperoxia during hypoglycemia would blunt baroreflex control of blood pressure and cardio-vagal tone. Ten young healthy adults were exposed to normoxia [PaO2 122 ± 3 mmHg] or hyperoxia [PaO2 424 ± 39] (to blunt cellular activation of the carotid body glomus cells) during a hyperinsulinemic-hypoglycemic clamp (2 mU/kg FFM/min; 3.33 mmol/L). Two 180 min hyperinsulinemic-hypoglycemic clamps were performed on each subject one week apart, randomized to either normoxia or hyperoxia (p<0.05). Blood pressure was monitored continuously via a brachial arterial catheter. Cardio-vagal tone was assessed via the high frequency (HF) component of heart rate variability from 5 min periods of 5-lead ECG recording under baseline (euglycemia) and hypoglycemia. Mean blood pressure during hypoglycemia was significantly lower with hyperoxia than with normoxia (delta reduction from baseline: -5.4 ± 3.4 mmHg normoxia vs. -13.8 ± 1.9 mmHg hyperoxia, p<0.05). The typical baroreflex-mediated rise in heart rate and sympathetic activity with lower blood pressure did not occur when the carotid bodies were silenced. Area under the curve values (expressed as % normoxia response) for catecholamines during hypoglycemia were significantly suppressed by hyperoxia (norepinephrine -50.7 ± 5.2%, epinephrine -62.6 ± 3.3%, p<0.05 vs normoxia). HF values decreased significantly from baseline during hypoglycemia, however this reduction was attenuated under hyperoxia (Normoxia: -69% vs. Hyperoxia: -41%, p=0.04). Heart rate increased significantly during hypoglycemia (Normoxia: 59.7 bpm ± 2.4 vs. 71.9 ± 4.0; Hyperoxia: 60.6 bpm ± 1.9 vs. 68.5 ± 3, p<0.001), however, this increase was not different between normoxia and hyperoxia despite differences in cardio-vagal tone, heart rate variability, and blood pressure. These data indicate that the carotid body chemoreceptors may be partially responsible for the reduction in cardio-vagal tone associated with hypoglycemia, and they provide evidence for a role of the carotid body chemoreceptors in parasympathetic tone to the heart and sympathetic mediation of the baroreflex. Together, these data support the idea that the carotid bodies play a role in heart rate variability and baroreflex control of blood pressure in humans. [ABSTRACT FROM AUTHOR]

Cerebrovascular reactivity determines the responsiveness of the cerebral vessels to vasoactive stimuli. However, acute changes in blood pressure may augment the calculated cerebrovascular reactivity. If autoregulatory mechanisms within the brain are intact, fluctuations in blood pressure will not alter cerebral blood flow. Because aging and hypertension may reduce autoregulation, cerebrovascular reactivity is often calculated using conductance to account for changes in mean arterial pressure (MAP). Yet, MAP may underestimate the influence of central hemodynamics on cerebral blood flow. In this context, we investigated whether central pulse wave characteristics were associated with cerebrovascular reactivity in healthy humans. Hypercapnia was used to determine cerebrovascular reactivity of the middle cerebral artery (MCA) in 28 adults (14 men and 14 women) using transcranial Doppler. MAP was measured using finger photoplethysmography and central pulse wave characteristics (i.e. aortic blood pressure, augmented pressure, augmentation index) were determined using arterial tonometry. Baseline MCA velocity was 48.6 ± 3.9 cm/s and cerebrovascular reactivity was 0.79 ± 0.08 AU. Aortic systolic (110 ± 2 mmHg) and diastolic (72 ± 1 mmHg) blood pressure were not associated with cerebrovascular reactivity. However, cerebrovascular reactivity was inversely associated with augmented pressure (8.3 ± 1.0 mmHg; r = -0.43; p<0.05), augmentation index (21.1 ± 2.3 %; r = -0.52; p<0.01), and augmentation index corrected for heart rate (12.1 ± 2.6%; r= -0.50; p<0.01). In conclusion, higher augmentation of the central pulse wave is associated with lower cerebrovascular reactivity in healthy adults. Our results suggest that cerebral blood flow regulation may be affected by central pulse wave characteristics. Funded by NIH RR-024150, AR-056950, AG-038067, and AG-16574-11PP2 [ABSTRACT FROM AUTHOR]

Background: Understanding age-related changes in blood pressure regulation is key to preventing and treating hypertension. The blood pressure error signal represents the difference between resting diastolic blood pressure (DBP) and the T50 value, the DBP at which 50% of cardiac cycles are associated with bursts of muscle sympathetic nerve activity (MSNA). We have previously shown that both the T50 and the error signal are different between young men and women, suggesting that sex hormones may have an important influence. The purpose of the present study was to evaluate whether T50 and the error signal relate to the extent of change in blood pressure during autonomic blockade (AB) in young and postmenopausal women. Methods: In 12 young women (YW; 25 ± 1 yrs) and 12 postmenopausal women (PM; 61 ± 2 yrs), we measured MSNA using microneurography, and intra-arterial brachial blood pressure before and during complete AB with trimethaphan camsylate. Relationships between MSNA, T50, error signal (T50-DBP) and ΔDBP with AB were measured using linear regression analysis and Pearson's correlation coefficient. For mean data comparison between YW and PM an unpaired t test was used. Results: ?DBP was associated with baseline T50 (r=-0.739, p<0.001), indicating that a greater reduction in DBP during AB was associated with higher T50 values in PM women (74.4±7.6 mmHg; r=-0.725, p=0.008) but not in young women (65.7±5.1 mmHg; r=-0.337, p=0.285). There was also an inverse relationship between ?DBP and the error signal, but only when all women are grouped together (r=-0.715, p<0.001). This means that women who operate at a higher BP than their T50 (i.e. a negative error signal) have a smaller change in DBP when autonomic tone is removed. Women with the most negative error signal (DBP much higher than T50) had the lowest average MSNA (r=0.910, p<0.001) in both groups (YW: r=0.886, p<0.001; PM: r=0.870, p<0.001). Young women had more negative error signals than PM women (-7.6±5.2 versus 2.1±4.6 mmHg, p<0.001; respectively), and lower average MSNA (15.5±4.9 versus 32.9±10.2 bursts/min, p<0.001; respectively). Conclusions: Using T50 and error signal analysis, we have identified important differences in control of MSNA between young and PM women. Postmenopausal women had higher T50 values, more positive error signals, and greater drops in DBP during autonomic blockade. These data are consistent with recent reports from our laboratory regarding greater autonomic support of blood pressure in PM women, and provide further evidence of the importance of reproductive hormone influences on sympathetic mechanisms controlling blood pressure in women. [ABSTRACT FROM AUTHOR]

Sex hormones are essential in the development of the biological and physiological sexual characteristics of males and females. However, it is well known that they also play an important role in modulating cardiovascular regulation, particularly with regard to regulation of arterial pressure. Recent comparative examinations of blood pressure regulation in healthy men and women have increased our understanding regarding normal blood pressure control and how sex /sex hormones might influence the development of cardiovascular diseases such as hypertension. Previous studies have shown that, under the age of 40, men and women do indeed regulate resting blood pressure differently. The sympathetic nervous system is central to blood pressure regulation in humans; despite this, basal levels of muscle sympathetic activity (MSNA, an estimate of central sympathetic outflow) are not related to resting blood pressure in either men or women. How can this be when MSNA causes vasoconstrictor tone? Interestingly, in young men MSNA is positively related to peripheral vascular resistance but inversely related to cardiac output. Consequently, men with high MSNA have a high vascular resistance but a lower cardiac output. This balance negates the effect of MSNA on resting blood pressure in men; so men with high MSNA can have a normal resting blood pressure. However, this balance does not exist in young women. In young pre-menopausal women, MSNA is not related to total peripheral resistance or cardiac output. Thus, it appears that basal levels of MSNA contribute little to resting peripheral vasoconstrictor tone. Importantly, this difference between men and women appears to change with age and menopausal status. In postmenopausal women, MSNA becomes directly related to peripheral vascular resistance and blood pressure. This provides strong evidence that sex and sex hormones might modulate how MSNA affects resting blood pressure. [ABSTRACT FROM AUTHOR]

Biomedical research relies on limited animal models to address questions related to human health. The limitations of inbred or genetically modified rodent models has become especially clear recently based on a number of high profile publications showing limited animal to human translation. Historically, many key discoveries have been generated by studies on a range of animals adapted to unusual environments. For example major advances in the understanding of the microcirculation continue to come from studies of the bat wing. In this context, the goal of this symposium is to explore what might be described as the "re-emergence" of comparative physiology to address important questions in human health and disease. It will also highlight sex differences in blood pressure regulation in humans. This talk will provide a brief historical overview of the issues outlined above and also highlight areas such as hypoxia tolerance, and maintenance of bone and muscle mass during extreme inactivity where there are comparative "solutions" to problems with high relevance to human health and disease. [ABSTRACT FROM AUTHOR]