Citations

Involuntary apnea during sleep elicits sustained arterial hypertension through sympathetic activation; however, little is known about voluntary apnea, particularly in elite athletes. Their physiological adjustments are largely unknown. We measured blood pressure, heart rate, hemoglobin oxygen saturation, muscle sympathetic nerve activity, and vascular resistance before and during maximal end-inspiratory breath holds in 20 elite divers and in 15 matched control subjects. At baseline, arterial pressure and heart rate were similar in both groups. Maximal apnea time was longer in divers (1.7±0.4 versus 3.9±1.1 minutes; P <0.0001), and it was accompanied by marked oxygen desaturation (97.6±0.7% versus 77.6±13.9%; P <0.0001). At the end of apnea, divers showed a >5-fold greater muscle sympathetic nerve activity increase ( P <0.01) with a massively increased pressor response compared with control subjects (9±5 versus 32±15 mm Hg; P <0.001). Vascular resistance increased in both groups, but more so in divers (79±46% versus 140±82%; P <0.01). Heart rate did not change in either group. The rise in muscle sympathetic nerve activity correlated with oxygen desaturation ( r 2 =0.26; P <0.01) and with the increase in mean arterial pressure ( r 2 =0.40; P <0.0001). In elite divers, breath holds for several minutes result in an excessive chemoreflex activation of sympathetic vasoconstrictor activity. Extensive sympathetically mediated peripheral vasoconstriction may help to maintain adequate oxygen supply to vital organs under asphyxic conditions that untrained subjects are not able to tolerate voluntarily. Our results are relevant to conditions featuring periodic apnea.

Among young normotensive men, a reciprocal balance between cardiac output and sympathetic nerve activity is important in the regulation of arterial pressure. In young women, the balance among cardiac output, peripheral resistance, and sympathetic nerve activity is unknown. Consequently, the aim of this study was to examine the relationship of cardiac output and total peripheral resistance to muscle sympathetic nerve activity in young women. Multiunit peroneal recordings of muscle sympathetic nerve activity were obtained in 17 women (mean±SEM: age 24±3 years) and 21 men (mean±SEM: age 25±5 years). Mean resting muscle sympathetic nerve activity was lower in women compared with men (19±3 versus 25±1 bursts minute −1 ; P <0.05), as was mean arterial pressure (89±1 versus 94±2 mm Hg; P <0.05). Mean arterial pressure was not related to muscle sympathetic nerve activity in men ( P =0.80) or women ( P =0.62). There was a positive relationship between total peripheral resistance and muscle sympathetic nerve activity ( r =0.62; P <0.05) and an inverse relationship between cardiac output and muscle sympathetic nerve activity ( r =−0.69; P <0.05) in men. Unexpectedly, muscle sympathetic nerve activity had no relationship to either total peripheral resistance ( r =−0.27; P >0.05) or cardiac output ( r =0.23; P >0.05) in women. Our results demonstrate that men and women rely on different integrated physiological mechanisms to maintain a normal arterial pressure despite widely varying sympathetic nerve activity among individuals. These findings may have important implications for understanding how hypertension and other disorders of blood pressure regulation occur in men and women.

OBJECTIVE— We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. RESEARCH DESIGN AND METHODS— Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18–30 years old) and older (59–76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot. RESULTS— Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals. CONCLUSIONS— The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.

Phenylethanolamine N-methyltransferase (PNMT) catalyzes the synthesis of epinephrine from norepinephrine. We previously identified and functionally characterized common sequence variation in the PNMT gene. In the present study, we set out to determine whether common PNMT genetic polymorphisms might be associated with individual variation in circulating epinephrine levels during exercise in 74 Caucasian American subjects. Circulating epinephrine levels were measured in each subject at baseline and during two different levels of exercise, ∼40% and ∼75% of peak workload. The PNMT gene was resequenced with DNA from each study subject. Eight novel PNMT polymorphisms were identified, including a C319T (Arg107Cys) nonsynonymous single nucleotide polymorphism (SNP) and I1G(280)A, a SNP located in the first intron of the gene. The I1G(280)A SNP was significantly associated with decreased exercise-induced circulating epinephrine levels and with a decreased epinephrine-to-norepinephrine ratio. The Cys107 recombinant allozyme displayed significantly lower levels of both PNMT activity and immunoreactive protein than the wild-type allozyme after transfection into COS-1 cells, but it did not appear to be associated with level of epinephrine in these subjects. Electrophoretic mobility shift and reporter gene assays performed with the I1G(280)A SNP indicated that this polymorphism could bind nuclear proteins and might modulate gene transcription. Our studies suggest that functionally significant variant sequence in the human PNMT gene might contribute to individual variation in levels of circulating epinephrine during exercise.

Despite being the subject of investigation for well over 100 years, the nature of exercising muscle blood flow control remains, in many respects, poorly understood. In this review we focus on the potential role of nitric oxide in vasodilation of muscle resistance vessels during a bout of exercise. Its contribution is explored in the context of whether it contributes to steady-state exercise hyperemia, the dynamic adjustment of muscle blood flow to exercise, or the modulation of sympathetic vasoconstriction in exercising muscle. It appears that the obligatory role of nitric oxide in all three of these categories is modest at best. The elucidation of the integrated nature of exercise hyperemia control in terms of synergy and redundancy of mechanism interaction remains in its infancy, and much more remains to be learned about the role of nitric oxide in this type of integrated control.

Patients with hypertension have a blunted sensitivity of baroreflex control of heart period. In these patients, baroreflex sensitivity is positively related to heart rate variability and inversely related to blood pressure variability. We hypothesized that this relationship would also be evident in healthy normotensive subjects and that individuals with higher baroreflex sensitivity would have lower ambulatory 24-hour blood pressure. Twenty-four-hour ambulatory blood pressure and heart rate were recorded in 50 healthy, normotensive, nonobese individuals (31 women and 19 men). The baroreflex was assessed using sequential bolus administration of sodium nitroprusside and phenylephrine, and baroreflex sensitivity was calculated as the slope of the relation between systolic blood pressure and R-R interval during the resulting blood pressure transients. Baroreflex sensitivity was inversely correlated to 24-hour average mean arterial pressure ( R =0.49; P <0.001) and positively related to daytime heart rate variability ( R =0.33; P =0.02). In contrast, no relationship was found between baroreflex sensitivity and 24-hour heart rate or blood pressure variabilities. We conclude that the relationship between baroreflex sensitivity and daytime heart rate variability was similar to that reported previously in hypertensive subjects. Furthermore, the inverse relation between baroreflex sensitivity and mean arterial pressure supports the idea that the baroreflex may exert longer-term effects on blood pressure than thought previously.

OBJECTIVE—Pioglitazone, a peroxisome proliferator–activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups. RESEARCH DESIGN AND METHODS—We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks. Body water content was measured with deuterated water, body composition by dual-energy X-ray absorptiometry and computed tomography, and cardiac output and systemic vascular resistance by acetylene rebreathing technique both before and after therapy. RESULTS—Pioglitazone increased (P &lt; 0.001 from baseline) total body water (+2.4 ± 0.5 l) accounting for 75% of the total weight gain (+3.1 ± 2.0 kg) but did not alter vascular endothelial growth factor concentrations. Total abdominal (−32.2 ± 19 cm2) and visceral fat area (−16.1 ± 8 cm2) tended to decrease with pioglitazone but increased (P &lt; 0.02 for differences between groups) with glipizide (+38.4 ± 17 cm2 abdominal; +19.1 ± 9 cm2 visceral). Pioglitazone tended to reduce (P = 0.05) diastolic (−8.4 ± 4 mmHg) and mean (−9.5 ± 5 mmHg; P = 0.08) blood pressure and reduced (P &lt; 0.001) systemic vascular resistance (2,785 ± 336 vs. 2,227 ± 136 dynes/s per m2), while there were no differences in these parameters with glipizide. Neither therapy altered circulating catecholamine concentrations. CONCLUSIONS—When pioglitazone and glipizide are given in doses sufficient to achieve equivalent glycemic control in people with type 2 diabetes, pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance.