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Introduction During cold exposure, an increase in sympathetic nerve activity evokes vasoconstriction (VC) of cutaneous vessels to minimize heat loss. In older adults, this reflex VC response is impaired thereby increasing their susceptibility to excess heat loss and hypothermia. Because l-tyrosine, the amino acid substrate necessary for catecholamine production, has been shown to augment reflex VC in age skin, we hypothesize that oral ingestion of l-tyrosine will attenuate the decline in core temperature (T c) during whole-body cooling in older adults. Methods In a randomized, double-blind design, nine young (25 ± 3 yr) and nine older (72 ± 8 yr) participants ingested either 150 mg·kg−1 of l-tyrosine or placebo before commencing 90 min of whole-body cooling to decrease skin temperature to approximately 29.5°C. Esophageal temperature and forearm laser Doppler flux (LDF) were measured continuously throughout the protocol to provide an index of T c and skin blood flow, respectively. The change in esophageal temperature (ΔT ES) was the difference in temperature at the end of cooling subtracted from baseline. Cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percent change from baseline (%ΔCVCBASELINE). Results Oral tyrosine ingestion augmented the cutaneous VC response to cooling in older adults (placebo, 14.4 ± 2.0; tyrosine, 32.7% ± 1.7% ΔCVCBASELINE; P < 0.05). Additionally, tyrosine improved T c maintenance throughout cooling in older adults (placebo, −0.29 ± 0.07; tyrosine, −0.07 ± 0.07 ΔT ES; P < 0.05). Both the cutaneous VC and T c during cooling were similar between young and older adults supplemented with tyrosine (P > 0.05). Conclusions These results indicate that l-tyrosine supplementation improves T c maintenance in response to acute cold exposure in an older population.

During cold exposure, reflex cutaneous vasoconstriction is an important thermoregulatory mechanism that minimizes heat loss. Laser Doppler flowmetry (LDF) is a widely used, non‐invasive method of assessing cutaneous microvascular blood flow. However, data on the reproducibility of LDF during a cooling stimulus is limited. Furthermore, various sampling depths of skin measurement are available depending on the type of LDF probe used; however, a comparison of different depths to the same cooling stimulus has not been determined. We hypothesized that LDF probes, particularly those sampling at deeper skin depths, would provide a reproducible measurement of cutaneous microvascular blood flow during whole‐body cooling. Fourteen healthy, young adults completed two whole‐body cooling bouts, each bout separated by 3‐7 days. Participants wore a water‐perfused whole‐body suit to reduce skin temperature (Tsk) from 34°C to 30.5°C over 30 minutes, and held at 30.5°C for an additional 10 minutes. LDF flux was measured continuously at five forearm sites using 1 VP1‐HP Doppler probe, 2 VP7b integrated probes, and 2 VP12 single point Dopplers (Moor Instruments, Axminster, UK) measuring at depths of 4.0 mm, 0.66 mm, and 0.33 mm, respectively. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure at each 0.5°C reduction in Tsk and at plateau. CVC values were expressed as percent changes from baseline (%ᐃCVCBASELINE). A greater vasoconstriction response was recorded using the VP1‐HP Doppler at plateau (34.7 ± 0.6%) compared to the VP7b (31.9 ± 0.5%, p < 0.001) and VP12 (30.3 ± 0.6%, p < 0.001) LDF probes. Additionally, test‐retest reproducibility between visits displayed good reproducibility (coefficient of variation <9%) among all three Doppler probes. These data indicate that LDF provides reproducible measurements during reflex cutaneous vasoconstriction at different depths. However, deeper Dopplers, which analyze a greater area of skin, are more likely to discriminate differences in cutaneous microvascular blood flow than those at shallower depths.

Women with a history of gestational diabetes mellitus (GDM) are at greater risk for cardiovascular disease (CVD) and type II diabetes mellitus (T2DM). Endothelium- and nitric oxide-dependent dilation are attenuated in the microvasculature of otherwise healthy women with a history of GDM and this reduction is mediated, in part, by increased oxidative stress. However, whether this attenuation also reduces insulin-mediated microvascular responses in these women is unknown. We hypothesized that 1) insulin-mediated vasodilation would be attenuated, and that 2) antioxidant treatment would increase these responses, in women with a history of GDM compared to matched women with a history of healthy pregnancy (HC). Nine HC (32±6 yrs.) and 8 GDM (33±6 yrs.) participated in 1 experimental visit. Three microdialysis fibers were placed in the ventral forearm for the local delivery of lactated Ringer’s (control), 15mM N G-nitro-L-arginine methyl ester (L-NAME; NO synthase-inhibition), or 5mM ascorbate (non-specific antioxidant). Following baseline measurements, increasing doses of insulin [10-8 -10-4 M] were added to the site-specific perfusates. Red blood cell flux was measured continuously with laser-Doppler flowmetry, and cutaneous vascular conductance was calculated (CVC=flux/MAP) and standardized to maximum (%CVC max; 28mM SNP + 43°C). Subjects with GDM had attenuated insulin-mediated vasodilation (GDM:16.0 ± 3.0 vs. HC: 31.3 ± 4.7 %CVCmax; p= 0.02) at the control site. L-NAME attenuated insulin-mediated dilation in HC (14.7 ± 3.5 %CVCmax, p=0.004) but not in GDM (12.2 ± 1.9 %CVCmax, p=0.48). Local ascorbate perfusion increased insulin-mediated dilation in GDM (27.6 ± 7.2 %CVCmax; p=0.04) but had no effect in HC (p=0.85). These data suggest that women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and that this attenuation is mediated, in part, by increased oxidative stress. Supported by The UI Fraternal Order of Eagles Diabetes Research Center This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences in the activation of the renin-angiotensin system (RAS) likely contribute to differences in cardiovascular outcomes in premenopausal women compared to age-matched men. It is established that women have a reduced activation of the vasoconstrictor angiotensin II – angiotensin II type 1 receptor (AT1R) pathway. Emerging evidence suggests that this may be mediated by a shift toward the more recently described vasodilatory RAS, including increased sensitivity of the vasodilatory angiotensin II type 2 receptor (AT2R). However, few in vivo studies have directly examined sex differences in AT2R-mediated dilation, or the balance between AT1R- and AT2R-mediated vascular responses in humans. Using the cutaneous microcirculation as a model, we hypothesized that AT2R-mediated dilation would be greater in premenopausal women compared to men, and that AT1R-blockade would augment AT2R-mediated dilation to a greater extent in men than in women. Eight healthy women (22±3 years) and 11 healthy men (23±5 years) participated in 1 experimental visit. Two intradermal microdialysis fibers were placed in the skin of the ventral forearm for graded infusions of either compound 21 (C21, AT2R agonist; 10-12 - 10-3 mol/L) alone or C21 + 43 μmol/L losartan (AT1R antagonist). Red blood cell flux was measured over each microdialysis site by laser-Doppler flowmetry. Cutaneous vascular conductance was calculated (CVC=doppler flux/mean arterial pressure) and normalized to maximum (%CVCmax; 28mM SNP+43°C). Women had a greater peak vasodilation response to C21 compared to men (27.2±5.7 versus 18.2±2.7 %CVCmax; p=0.03). AT1R-inhibition augmented peak C21-mediated dilation in men (31.3±4.5 versus 18.2±2.7 %CVCmax; p=0.009) but had no effect in women (24.5±6.5 versus 27.2±5.7 %CVCmax; p=0.34). These data suggest that premenopausal women have a greater AT2R-mediated vasodilation response than men, and that AT1R activation inhibits AT2R-mediated dilation in men, but not in women. This study is supported by National Heart, Lung, and Blood Institute Grant R00HL138133. Clinicaltrials.gov identifier: NCT05576155 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.