The Effects of Noradrenergic Antagonism on Skin Vascular Control in Females Using Oral Contraceptives
Authors: Martin Zachary T. , Hodges Gary J. , Del Pozzi Andrew T. 
Published: November 2023

Vasodilation and vasoconstriction of the cutaneous microcirculation play a major role in human thermoregulation. Since cutaneous vascular function is known to differ between males and females, the mechanisms behind these differences need to be investigated. Additionally, female oral contraceptive (OCP) use is quite common and its effects on thermoregulation are unknown.

PURPOSE

To determine the contributions of noradrenaline (NA) and neuropeptide Y (NPY) to basal vascular tone and vasodilation in response to local forearm heating. In addition, we aimed to determine the effects of estrogen and progesterone on vascular responses by testing the female participants during low (LH) and high hormone (HH) phases of OCP use.

METHODS

Six female and 6 male volunteers had 4 sites on 1 forearm prepared with microdialysis fibers, local skin heaters, and laser‐Doppler probes. Blood pressure was assessed every 5 min throughout the study. Microdialysis fibers were infused with one of the following solutions: lactated Ringer's solution (study vehicle), yohimbine and propranolol (YP), BIBP‐3226 (BIBP), and bretylium tosylate (BT). Baseline (33 °C) SkBF data were collected for 10 min via laser‐Doppler flowmetry (LDF). Local heating was initiated at a rate of 1 °C · 20 s−1 from 33 °C to 42 °C and was held for 35 min. Heaters were then set to 43 °C, in combination with an infusion of sodium nitroprusside, to induce maximal SkBF. LDF data were continuously collected at 50 Hz and processed offline. Raw LDF (mV), were converted to cutaneous vascular conductance (CVC) by dividing LDF values by the mean arterial pressure (mm Hg), then expressed as a percentage of maximal CVC (%CVCmax). Repeated measure ANOVAs were utilized to analyze differences in cutaneous vascular conductance. Statistical significance was set at p < 0.05.

RESULTS

Baseline (33 °C): For BIBP, compared to control, CVC for females in the HH phase (9 ± 1%max vs 10 ± 1%max) LH phase (7 ± 1% max vs 8 ± 1%max) did not differ (p > 0.05 for both); CVC in males was significantly higher (12 ± 1%max vs 8 ± 1%max; p < 0.05). With YP treatment, HH females had significantly higher, p < 0.05, CVC (19 ± 2%max) compared to LH females (12 ± 2%max). With BT treatment, females in the HH phase had significantly higher, p < 0.05, (19 ± 3%max) CVC than LH females (11 ± 1%max). Initial Peak (42 °C): For BIBP treatment, CVC in males was lower (65 ± 1%max) than HH (75 ± 2%max) and LH (72 ± 2%max) females.

CONCLUSION

NPY Y1 receptor antagonism resulted in significantly higher baseline SkBF in males compared to females. Thus, NPY does not appear to play a role in basal vascular function in females. NA receptor antagonism and presynaptic blockade of sympathetic neurotransmitters at baseline resulted in an increased SkBF response for HH females compared to LH females. Thus, NA appears to play a far greater role in vascular function during the HH phase of OCP use. The SkBF response to local heating was reduced in males who had NPY blockade when compared to females in both hormone phases. Therefore, NPY does not appear to play a role in the increase of SkBF in response to local heating nor in basal vascular function of females during LH and HH phases of OCP use.