Objective: Vascular tone is dictated by the net balance of vasodilatory and vasoconstrictor influences. During hypoxia, systemic sympathetic vasoconstrictor activity is increased but peripheral vasodilation prevails — suggesting vasodilatory factors outweigh sympathetically-mediated vasoconstrictor influences in the healthy state. Given vascular β-adrenergic receptors contribute to hypoxic vasodilation, we hypothesized pharmacological blockade of β-adrenergic receptors would augment the vasoconstrictor response to acute sympathetic activation during hypoxia. Methods: Thirteen young healthy participants (5F/8M, 27±7 yr, 25±3 kg/m2) completed two study visits randomized and blinded to oral placebo or propranolol (1mg/kg, NCT05256069). On each visit, participants completed two trials: 1) 10-min normoxia (0.21 FiO2, 98±0% SpO2) followed by sympathetic activation via a 2-min normoxic cold pressor test (CPT); 2) 5-min steady-state hypoxia (0.10±0.01 FiO2, 81±1% SpO2) followed by a 2-min hypoxic CPT. Forearm blood flow (FBF, venous occlusion plethysmography) and blood pressure (BP, finger photoplethysmography) were assessed. FBF was normalized for mean BP (forearm vascular conductance, FVC). A change in FVC from steady-state to the last 1-min of CPT was calculated (ΔFVC = CPT − steady-state) and expressed as a percent change (%FVC = ΔFVC/steady-state x 100). Results: The vascular response to sympathetic activation (CPT) was unaffected by hypoxia under placebo conditions (normoxia: -34±21%; hypoxia: -29±32%, p=0.33). In contrast, following β-adrenergic blockade with oral propranolol, sympathetically-mediated vasoconstriction was augmented during hypoxia (normoxia: -29±30%; hypoxia: -40±27%, p=0.04). Conclusion: β-adrenergic receptor blockade augments the vasoconstrictor response to acute sympathetic activation during hypoxia in a mixed-sex cohort. These preliminary data indicate functional β-adrenergic receptors are required to restrain sympathetically-mediated vasoconstriction during hypoxia. Based on data supporting sex-related differences in adrenergic control of vascular tone, future work will seek to stratify results by sex. Funding: AHA 909014 (DWJ), APS-SURF (BJB), HL153523 (JKL). This is the full abstract presented at the American Physiology Summit 2024 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.

Objective: Systemic insulin increases muscle sympathetic nervous system activity (MSNA) in healthy adults by augmenting firing frequency of medium-sized sympathetic action potentials (AP) and recruiting previously latent, larger axons. Whether these neural coding patterns are due to central or peripheral effects of insulin is unclear. We examined the impact of elevated central insulin on AP firing patterns in healthy adults. We hypothesized intranasal insulin administration, which increases central insulin levels, would increase MSNA via elevated firing frequency of APs and recruitment of previously latent, larger axons. Methods: Ten participants were assigned to time control [TC, n=6 (3M/3F)] or 160 IU of intranasal insulin [n=4 (3M/1F)] administered over 5 min. MSNA (fibular microneurography) was assessed at baseline and for 30 min following insulin administration. Sympathetic APs were identified using a matched mother wavelet and continuous wavelet transform. APs were divided into the proportion of those firing in small, medium, or large amplitude clusters. AP firing frequency, percent of APs firing within an MSNA burst (synchronous), and the probability of clusters firing more than once within an MSNA burst were identified. Data are reported as median (interquartile range). Results: MSNA burst frequency increased 15 min after intranasal insulin administration [24(20) to 31(23) bursts/min, p=0.03]. At this time, the percent of synchronous APs [72(27) to 90(24)%, p=0.02] and the probability of medium-sized AP clusters firing more than once within an MSNA burst [13(14) to 19(17)%, p=0.03] increased. No changes in MSNA burst frequency [23(14) to 25(13) bursts/min, p=0.27], percent of synchronous APs [74(15) to 75(34), p=0.48], nor firing probability of medium-sized AP clusters [6(12) to 8(7)%, p=0.97] occurred in TC. The total number of detected clusters did not change in either group (p>0.05). Conclusions: Intranasal insulin increases MSNA burst frequency due to a higher percent of synchronous APs, particularly medium-sized AP clusters; however, we did not observe recruitment of latent, larger axons. These exploratory data highlight potential differences in the sympathetic response to central versus peripheral insulin exposure in healthy adults. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 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.

Introduction: Hypoxia elicits peripheral vasodilation to preserve oxygen delivery to tissues. Approximately 10% of hypoxic vasodilation has been attributed to β-adrenergic receptors on the vascular endothelium and smooth muscle. Based on data supporting greater vascular β-adrenergic receptor responsiveness in females compared to males, we examined the effect of sex on the relative contribution of the β-adrenergic receptors to hypoxic vasodilation. We hypothesized β-adrenergic receptor blockade (oral propranolol, 1 mg/kg) would attenuate hypoxic vasodilation and the effect would be greater in females compared to males. Methods: Five female (26±8 yrs, 22±2 kg/m2) and eight male (27±7 yrs, 26±2 kg/m2) participants completed two randomized, single-blinded, and placebo-controlled visits (NCT05256069). On each visit (placebo, propranolol), forearm blood flow (venous occlusion plethysmography) and blood pressure (BP, finger photoplethysmography) were measured during normoxia (SpO2 ~98%) and hypoxia (SpO2 ~80%). Blood flow was normalized for mean BP and expressed as forearm vascular conductance (FVC). The relative change in FVC with hypoxia (%FVC = Hypoxia − Normoxia / Normoxia x 100) was assessed as an index of hypoxic vasodilation. Differences in %FVC between study visits (propranolol − placebo) are reported. Results: %FVC was unaffected by β-adrenergic blockade in female (placebo 15±14%, propranolol -1±15%, p=0.066) and male (placebo 19±25%, propranolol 16±15%, p=0.755) participants. Any effect of β-adrenergic receptor blockade on hypoxic vasodilation did not differ by sex (females: -16±14%, males -3±29%; p=0.383). Conclusion: These preliminary data suggest any effect of β-adrenergic receptor blockade on hypoxic vasodilation does not differ between young healthy female and male participants, although studies are ongoing. Our results further understanding of the effect of sex on vascular control mechanisms during hypoxia. Funding: AHA 909014 (DWJ), APS-SURF (BJB), HL153523 (JKL). This is the full abstract presented at the American Physiology Summit 2024 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.

Objective: Vascular compliance is an essential component of cerebral blood flow regulation. Prior work has shown cerebral vasodilation (elicited by hypercapnia) reduces cerebrovascular compliance (Ci); however, this work has yet to be translated to other vasoactive compounds. Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Herein, we hypothesized both peripheral (intravenous) and central (intranasal) insulin administration would increase indices of cerebral blood flow and reduce Ci in healthy young adults. Methods: Twenty-five healthy young adults (8 female; 26±7 yrs, 25±3 kg/m2) were assigned to two separate protocols (NCT05244694, NCT05153395). Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) was measured at baseline and under two study conditions: 1) at the end of a 60 min hyperinsulinemic euglycemic infusion, and 2) 60 min following 160 IU of intranasal insulin. Indices of Ci were calculated using a modified Windkessel model applied to blood pressure (finger photoplethysmography) and corresponding MCAv waveforms collected over a 5-min period (10 waveforms) at baseline and during the aforementioned insulin conditions. Results: Blood glucose remained unchanged throughout both protocols (both p>0.05). MCAv was maintained over time under both insulin conditions (protocol 1: 60±13 to 62±17 cm/s, p=0.635; protocol 2: 58±9 to 53±14 cm/s, p=0.146). In contrast, Ci decreased (0.00028±0.00010 to 0.00021±0.00007 cm/s/mmHg, p=0.010) from baseline during peripheral (intravenous) insulin administration. No change in Ci (0.00049±0.00025 to 0.00040±0.00018 cm/s/mmHg, p=0.189) were observed following intranasal insulin administration. Conclusions: Contrary to our hypothesis, there was no effect of peripheral or central insulin administration on resting MCAv in healthy young adults. However, intravenous (but not intranasal) insulin reduced Ci by approximately 25% from baseline values. These findings advance our understanding of cerebrovascular control mechanisms during insulin exposure and provide the opportunity to extend this work to diseased states characterized by insulin resistance, including diabetes. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 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.