Circadian Variation of α1-Adrenoceptor-mediated Pressor Response to Phenylephrine in Man

Tham, T. C. K.; Guy, S.; Riddell, James; Shanks, R. G.; Harron, D. W. G.

doi:10.1111/j.2042-7158.1996.tb05967.x

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…Indeed, it is even possible that the balance of norepinephrine and cotransmitter release might be affected in a circadian pattern, as it is between phases of the menstrual cycle (19). There are observations suggestive of a diurnal effect on ␣-adrenoceptor function such that the pressor response to the adrenergic agonist phenylephrine was significantly greater in the afternoon and evening than in the morning (23). If true for the cutaneous vasculature, equal sympathoexcitation from cooling in the PM would lead to a greater vasoconstrictor response.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous vasoconstrictor response to whole body skin cooling is altered by time of day

Aoki

Stephens

Saad

et al. 2003

Journal of Applied Physiology

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To test for a diurnal difference in the vasoconstrictor control of the cutaneous circulation, we performed whole body skin cooling (water-perfused suits) at 0600 (AM) and 1600 (PM). After whole body skin temperature (T(sk)) was controlled at 35 degrees C for 10 min, it was progressively lowered to 32 degrees C over 18-20 min. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry at three control sites and at a site that had been pretreated with bretylium by iontophoresis to block noradrenergic vasoconstriction. After whole body skin cooling, maximal cutaneous vascular conductance (CVC) was measured by locally warming the sites of SkBF measurement to 42 degrees C for 30 min. Before whole body skin cooling, sublingual temperature (T(or)) in the PM was significantly higher than that in the AM (P < 0.05), but CVC, expressed as a percentage of maximal CVC (%CVC(max)), was not statistically different between AM and PM. During whole body skin cooling, %CVC(max) levels at bretylium-treated sites in AM or PM were not significantly reduced from baseline. In the PM, %CVC(max) at control sites fell significantly at T(sk) of 34.3 +/- 0.01 degrees C and lower (P < 0.05). In contrast, in the AM %CVC(max) at control sites was not significantly reduced from baseline until T(sk) reached 32.3 +/- 0.01 degrees C and lower (P < 0.05). Furthermore, the decrease in %CVC(max) in the PM was significantly greater than that in AM at T(sk) of 33.3 +/- 0.01 degrees C and lower (P < 0.05). Integrative analysis of the CVC response with respect to both T(or) and T(sk) showed that the cutaneous vasoconstrictor response was shifted to higher internal temperatures in the PM. These findings suggest that during whole body skin cooling the reflex control of the cutaneous vasoconstrictor system is shifted to a higher internal temperature in the PM. Furthermore, the slope of the relationship between CVC and T(sk) is steeper in the PM compared with that in the AM.

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Section: Discussionmentioning

confidence: 99%

Cutaneous vasoconstrictor response to whole body skin cooling is altered by time of day

Aoki

Stephens

Saad

et al. 2003

Journal of Applied Physiology

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“…These authors suggested that this difference is due to a diurnal rhythm in vasoconstrictor activity (16). By contrast, ␣-adrenoceptor-mediated vascular responses to the same doses of phenylephrine (an ␣-adrenergic agonist) in the morning were significantly lower than in the evening or night (26). In addition, plasma epinephrine and norepinephrine in humans peak in the early morning (14).…”

Section: Discussionmentioning

confidence: 99%

Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress

Aoki

Stephens

Johnson

2001

American Journal of Physiology-Regulatory, Integrative and Comp

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It is not clear whether the diurnal variation in the cutaneous circulatory response to heat stress is via the noradrenergic vasoconstrictor system or the nonadrenergic active vasodilator system. We conducted whole body heating experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow was monitored by laser-Doppler flowmetry at control sites and at sites pretreated with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood pressure was used to calculate cutaneous vascular conductance. The sublingual temperature (T(or)) threshold for cutaneous vasodilation was significantly higher in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal shift in threshold depends on the active vasodilator system. The slope of cutaneous vascular conductance as a percentage of its maximum with respect to T(or) was significantly lower in AM at control sites only. Also, in the AM, the slope at control sites was significantly lower than that at BT-treated sites (P < 0.05), suggesting that the diurnal change in the sensitivity of cutaneous vasodilation depends on vasoconstrictor system function. Overall, the diurnal variation in the reflex control of skin blood flow during heat stress involves both vasoconstrictor and active vasodilator systems.

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“…Phenylephrine infusions are used to sustain blood pressure at clinically acceptable levels during anesthesia. Inter-individual differences in response to phenylephrine have been frequently observed in clinical practice [2–4]. Patients’ response to phenylephrine may vary depending upon age, co-morbidities (e.g., cardiovascular diseases), concurrent medications, and anesthetic status.…”

Section: Introductionmentioning

confidence: 99%

Dissecting genetic factors affecting phenylephrine infusion rates during anesthesia: a genome-wide association study employing EHR data

Zhang¹,

Poler

Li³

et al. 2019

BMC Med

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Background The alpha-adrenergic agonist phenylephrine is often used to treat hypotension during anesthesia. In clinical situations, low blood pressure may require prompt intervention by intravenous bolus or infusion. Differences in responsiveness to phenylephrine treatment are commonly observed in clinical practice. Candidate gene studies indicate genetic variants may contribute to this variable response. Methods Pharmacological and physiological data were retrospectively extracted from routine clinical anesthetic records. Response to phenylephrine boluses could not be reliably assessed, so infusion rates were used for analysis. Unsupervised k -means clustering was conducted on clean data containing 4130 patients based on phenylephrine infusion rate and blood pressure parameters, to identify potential phenotypic subtypes. Genome-wide association studies (GWAS) were performed against average infusion rates in two cohorts: phase I ( n = 1205) and phase II ( n = 329). Top genetic variants identified from the meta-analysis were further examined to see if they could differentiate subgroups identified by k -means clustering. Results Three subgroups of patients with different response to phenylephrine were clustered and characterized: resistant (high infusion rate yet low mean systolic blood pressure (SBP)), intermediate (low infusion rate and low SBP), and sensitive (low infusion rate with high SBP). Differences among clusters were tabulated to assess for possible confounding influences. Comorbidity hierarchical clustering showed the resistant group had a higher prevalence of confounding factors than the intermediate and sensitive groups although overall prevalence is below 6%. Three loci with P < 1 × 10 −6 were associated with phenylephrine infusion rate. Only rs11572377 with P = 6.09 × 10 −7 , a 3′UTR variant of EDN2 , encoding a secretory vasoconstricting peptide, could significantly differentiate resistant from sensitive groups ( P = 0.015 and 0.018 for phase I and phase II) or resistant from pooled sensitive and intermediate groups ( P = 0.047 and 0.018). Conclusions Retrospective analysis of electronic anesthetic records data coupled with the genetic data identified genetic variants contributing to variable sensitivity to phenylephrine infusion during anesthesia. Although the identified top gene, EDN2 , has robust biological relevance to vasoconstriction by binding to endothelin type A (ET A ) receptors on arterial smooth muscle cells, further functional as well as replication studies are necessary to confirm this association. Electronic supplementary...

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Circadian Variation of α1-Adrenoceptor-mediated Pressor Response to Phenylephrine in Man

Cited by 5 publications

References 11 publications

Cutaneous vasoconstrictor response to whole body skin cooling is altered by time of day

Cutaneous vasoconstrictor response to whole body skin cooling is altered by time of day

Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress

Dissecting genetic factors affecting phenylephrine infusion rates during anesthesia: a genome-wide association study employing EHR data

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