Jordan C. Patik

Influence of sex on microvascular and macrovascular responses to prolonged sitting

Increased daily sitting time is associated with greater cardiovascular risk, and, on average, women are more sedentary than men. Recent reports have demonstrated that prolonged sitting reduces lower leg microvascular (reactive hyperemia) and macrovascular [flow-mediated dilation (FMD)] vasodilator function. However, these studies have predominately included men, and the effects of sitting in young women are largely unexplored. This becomes important given known sex differences in vascular function. Thus, herein, we assessed popliteal artery reactive hyperemia and FMD before and after a 3-h sitting period in healthy young women (n = 12) and men (n = 8). In addition, resting popliteal artery hemodynamics (duplex Doppler ultrasound) and calf circumference were measured before, during, and after sitting. Resting popliteal artery shear rate was reduced to a similar extent in both groups during the sitting period (women: -48.5 ± 8.4 s-1 and men: -52.9 ± 12.3 s-1, P = 0.45). This was accompanied by comparable increases in calf circumference in men and women (P = 0.37). After the sitting period, popliteal artery FMD was significantly reduced in men (PreSit: 5.5 ± 0.9% and PostSit: 1.6 ± 0.4%, P < 0.001) but not women (PreSit: 4.4 ± 0.6% and PostSit: 3.6 ± 0.6%, P = 0.29). In contrast, both groups demonstrated similar reductions in hyperemic blood flow area under the curve (women: -28,860 ± 5,742 arbitrary units and men: -28,691 ± 9,685 arbitrary units, P = 0.99), indicating impaired microvascular reactivity after sitting. These findings indicate that despite comparable reductions in shear rate during 3 h of uninterrupted sitting, macrovascular function appears protected in some young women but the response was variable, whereas men exhibited more consistent reductions in FMD. In contrast, the leg microvasculature is susceptible to similar sitting-induced impairments in men and women.NEW & NOTEWORTHY We demonstrate that leg macrovascular function was consistently reduced in young men but not young women after prolonged sitting. In contrast, both men and women exhibited similar reductions in leg microvascular reactivity after sitting. These data demonstrate, for the first time, sex differences in vascular responses to prolonged sitting.

Exaggerated Vasoconstriction to Spontaneous Bursts of Muscle Sympathetic Nerve Activity in Healthy Young Black MenNovelty and Significance

Blacks have the highest prevalence of hypertension, putting them at greater risk of cardiovascular disease and death. Previous studies have reported that, relative to whites, healthy black men have augmented pressor responses to sympathoexcitatory stressors. Although important, these studies do not inform about the resting state and the influence of spontaneous changes in resting muscle sympathetic nerve activity (MSNA). Likewise, little is known about the transduction of MSNA into a vascular response at rest on a beat-to-beat basis. Accordingly, we tested the hypothesis that relative to whites, blacks would exhibit greater vasoconstriction and pressor responses following spontaneous bursts of MSNA. Mean arterial pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 minutes of supine rest in 35 young healthy men (17 blacks and 18 whites). Signal averaging was used to characterize changes in leg vascular conductance, total vascular conductance, and mean arterial pressure following spontaneous MSNA bursts. Blacks demonstrated significantly greater decreases in leg vascular conductance (blacks: −15.0±1.0%; whites: −11.5±1.2%; P=0.042) and total vascular conductance (blacks: −8.6±0.9%; whites: −5.1±0.4%; P=0.001) following MSNA bursts, which resulted in greater mean arterial pressure increases (blacks: +5.2±0.6 mm Hg; whites: +3.9±0.3 mm Hg; P=0.04). These exaggerated responses in blacks compared with whites were present whether MSNA bursts occurred in isolation (singles) or in combination (multiples) and were graded with increases in burst height. Collectively, these findings suggest that healthy young black men exhibit augmented sympathetic vascular transduction at rest and provide novel insight into potential mechanism(s) by which this population may develop hypertension later in life.African Americans (AA) have the highest prevalence of hypertension, putting them at greater risk of cardiovascular disease and death. Previous studies have reported that, relative to Caucasian Americans (CA), healthy AA men have augmented pressor responses to sympatho-excitatory stressors. While important, these studies do not inform about the resting state and the influence of spontaneous changes in resting muscle sympathetic nerve activity (MSNA). Likewise, little is known regarding the transduction of MSNA into a vascular response at rest on a beat-to-beat basis. Accordingly, we tested the hypothesis that relative to CA, AA would exhibit greater vasoconstriction and pressor responses following spontaneous bursts of MSNA. Mean arterial pressure (MAP), common femoral artery blood flow, and MSNA were continuously recorded during 20 minutes of supine rest in 35 young healthy men (17 AA and 18 CA). Signal-averaging was used to characterize changes in leg (LVC) and total vascular conductance (TVC) and MAP following spontaneous MSNA bursts. AA demonstrated significantly greater decreases in LVC (AA: -15.0±1.0, CA: -11.5±1.2%; P=0.042) and TVC (AA: -8.6±0.9, CA: -5.1±0.4%; P=0.001) following MSNA bursts, which resulted in greater MAP increases (AA: +5.2±0.6, CA: +3.9±0.3 mmHg; P=0.04). These exaggerated responses in AA compared to CA were present whether MSNA bursts occurred in isolation (singles) or in combination (multiples) and were graded with increases in burst height. Collectively, these findings suggest that healthy young AA men exhibit augmented sympathetic vascular transduction at rest, and provide novel insight into potential mechanism(s) by which this population may develop hypertension later in life.

Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.

It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringers solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2‑boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 μl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ± 12 vs. AA: 62 ± 6 vs. %CVCmax; P < 0.001). This response was improved in AA at the l-arginine site (Control: 62 ± 6 vs. l-arginine: 70 ± 18%CVCmax; P < 0.05) but not in the arginase inhibited site (Control: 62 ± 6 vs. Arginase inhibited: 62 ± 13%CVCmax; P = 0.91). In addition, the AA group had an attenuated NO contribution to the plateau phase during 42 °C local heating relative to the CA group (CA: 56 ± 14 vs. AA: 44 ± 6 Δ %CVCmax; P < 0.001). These findings suggest that 1) cutaneous microvascular function in response to local heating is blunted in young AA when compared to age-matched young CA; 2) this attenuated response is partly related to decrease in NO bioavailability in young AA; and 3) a local infusion of l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA.

Age‐related microvascular dysfunction: novel insight from near‐infrared spectroscopy

What is the central question of this study? Can near‐infrared spectroscopy (NIRS)‐derived post‐occlusion tissue oxygen saturation recovery kinetics be used to study age‐related impairments in microvascular function? What is the main finding and its importance? Using a previously established 5 min cuff occlusion protocol, we found that NIRS‐derived indices of microvascular function were markedly reduced in elderly compared with young participants. However, when we controlled for the absolute level of vasodilatory stimulus and matched the tissue desaturation level between groups, we found similar responses in young and elderly participants. Overall, these data highlight the important role NIRS can serve in clinical vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.

Fast-food meal reduces peripheral artery endothelial function but not cerebral vascular hypercapnic reactivity in healthy young men

Consumption of a representative fast‐food meal (FFMeal) acutely impairs peripheral conduit artery vascular function; however, the effect on cerebral vascular function remains unknown. This study tested the hypothesis that a FFMeal would impair cerebral vascular function as indexed by an attenuated increase in cerebral vascular conductance (CVCI) in the middle cerebral artery (MCA) during a hypercapnic challenge. Ten healthy men (age: 24 ± 3 years, BMI: 24.3 ± 3.8 kg/m2) were studied under two conditions; a standardized FFMeal (990 kcals, 50% fat, 36% carbohydrate, 14% protein, and 2120 mg sodium) and a fasting control condition. Basal hemodynamics, cerebral vasomotor reactivity (CVMR), and brachial artery flow‐mediated dilation (BA FMD) were completed after an overnight fast (Pre) and again 2 h and 4 h later both days. To assess CVMR, subjects rebreathed from a 5‐L bag while MCA velocity (MCAVmean) was measured using transcranial Doppler (TCD) ultrasound and converted into CVCI (MCAVmean/mean arterial pressure). Peripheral artery endothelial function was assessed via BA FMD following a standard 5‐min occlusion protocol. As expected, BA FMD was reduced at 2 h (Pre: 6.6 ± 1.7% vs. 5.2 ± 1.8%, P = 0.01). However, despite significant impairment in BA FMD, neither peak CVCI%baseline nor CVMR was affected by the FFMeal (Control–Pre: 1.9 ± 1.1, 2 h: 2.1 ± 1.1, 4 h: 1.7 ± 1.1 ∆CVCI%·∆PETCO2−1 vs. FFMeal–Pre: 2.1 ± 1.1, 2 h: 2.2 ± 0.7, 4 h: 1.9 ± 0.9 ∆CVCI%·∆PETCO2−1, time × condition P = 0.88). These results suggest that cerebral vascular reactivity to hypercapnia in healthy young men is not altered by an acute FFMeal.

Racial Differences in Vascular Function in Response to Mental Stress: 2224 Board #60 June 1 11

African Americans (AA) have a higher prevalence of hypertension and other cardiovascular (CV) complications compared to other populations. While the reasons for this elevated CV disease risk are multifactorial, vascular dysfunction is a key contributing factor. It has been previously shown that mental stress, induced by mental arithmetic, results in a significant increase in forearm blood flow (FBF). This response has been predominantly attributed to the release and vasodilatory effect of Nitric Oxide (NO). In this regard, a previous study has reported that AA have an attenuated increase in FBF as compared to Caucasians (CA) in response to mental stress, which may be related to impaired vascular function and thus elevated CV disease risk in AA. However, this study was conducted in a middle-age cohort (mid to late 40’s). Whether this attenuation is present in a young relatively healthy population is unknown. PURPOSE: The purpose of this study was to test the hypothesis that the vasodilatory response to mental stress is blunted in a relatively young and healthy AA population. METHODS: 6 relatively healthy young AA and 6 CA males (AA age: 22 + 2.6, CA age: 23 + 4.6) participated in this study. All measurements were obtained in the morning following an overnight fast. Brachial artery diameter and blood velocity were assessed using high resolution duplex ultrasound. Mental stress was induced by asking subjects to subtract 7 continuously from a 3-digit number while attempting to report answers at a pace set by a 60 bpm metronome. The 3-digit number was changed at 20 second intervals. FBF was measured during a two minute baseline followed by 3 minutes of mental stress. Vascular function was assessed as the absolute peak blood flow response (ml/min) as well as peak conductance (ml/min/mmHg) during the mental stress. RESULTS: The absolute peak flow (AA: 183 + 39 ml/min, CA: 307 + 127 ml/min; P = 0.05) were significantly greater in CA compared to AA. The maximum increase in conductance (AA: 2.03 + 0.32 ml/min/mmHg, CA: 3.69 + 1.39 ml/min/mmHg; P = .02) was also significantly higher in CA as compared to AA. CONCLUSION: This preliminary data supports our hypothesis that vascular function in response to mental stress is attenuated in young healthy AA as compared to their CA counterparts.

Sex differences in the mechanisms mediating blunted cutaneous microvascular function in young black men and women

The black population exhibits attenuated vasodilatory function across their lifespan, yet little is known regarding the mechanisms of this impairment. Recent evidence suggests a potential role for oxidative stress. Therefore, we tested the hypothesis that NADPH oxidase (NOX) and/or xanthine oxidase (XO) contribute to blunted nitric oxide (NO)-mediated cutaneous microvascular function in young black adults. In 30 white and black subjects (8 men and 7 women in each group), local heating was performed while NOX and XO were inhibited by apocynin and allopurinol, respectively, via intradermal microdialysis. The plateau in cutaneous vascular conductance (red blood cell flux/mean arterial pressure) during 39°C local heating at each site was compared with a control site perfused with lactated Ringer solution. Subsequent inhibition of NO synthase via Nω-nitro-l-arginine methyl ester allowed for quantification of the NO contribution to vasodilation during heating. Black individuals, relative to white individuals, had a blunted cutaneous vascular conductance plateau at the control site (45 ± 9 vs. 68 ± 13%max, P < 0.001) that was increased by both apocynin (61 ± 15%max, P < 0.001) and allopurinol (58 ± 17%max, P = 0.005). Black men and black women had similar responses to heating at the control site ( P = 0.99), yet apocynin and allopurinol increased this response only in black men (both P < 0.001 vs. control). The NO contribution was also increased via apocynin and allopurinol exclusively in black men. These findings suggest that cutaneous microvascular function is reduced because of NOX and XO activity in black men but not black women, identifying a novel sex difference in the mechanisms that contribute to blunted vascular responses in the black population. NEW & NOTEWORTHY We demonstrate that cutaneous microvascular responses to local heating are consistently reduced in otherwise healthy young black men and women relative to their white counterparts. Inhibition of NADPH oxidase and xanthine oxidase via apocynin and allopurinol, respectively, augments microvascular function in black men but not black women. These data reveal clear sex differences in the mechanisms underlying the racial disparity in cutaneous microvascular function.