Search

Problem Too much or too little gestational weight gain (GWG) can negatively impact maternal and fetal health, according to Institute of Medicine Guidelines. Background Health care providers are key players in providing reliable evidence-informed prenatal advice related to appropriate GWG. However, there appears to be inconsistent GWG communication among healthcare providers during prenatal care. Aim To determine pregnant women and new mothers’ perceptions of healthcare provider GWG and dietary counselling during the pregnancy period. Methods A reliable and validated cross-sectional electronic survey was administered to currently pregnant women and women who had recently given birth. The web-based questionnaire was self-administered and took 10–25 min. Findings A total of 1507 eligible women participated in the survey. More than half (57%) reported that their healthcare provider talked to them about personal weight gain limits. Of these participants, about a third (34%) of participants were counselled regularly at each or most visits. Among the women that were not counselled on personal GWG limits, over half (56%) reported that healthcare provider guidance would have been helpful to achieve their target weight. Less than half (45%) of participants reported that their healthcare providers discussed dietary requirements or changes in pregnancy. Discussion These findings highlight areas for improvement in prenatal dialogue, which can support better outcomes for both mother and baby. Conclusion A better understanding of pregnant and mothers’ perceptions about weight and diet counselling is needed to understand what may need greater attention and clarification and to improve such dialogue.

Summary Introduction Abnormal renal development that results in lack of function or development of one of two kidneys is known as congenital solitary functioning kidney (CSFK). Two well characterized sub-categories of CFSK are unilateral renal agenesis (URA) and multicystic dysplastic kidney (MCDK). This systematic review sought to evaluate the change in renal function in children ≤ 18 years old with a CSFK as a result of URA or MCDK. Methods A literature search in MEDLINE and Embase was conducted (1946 to July 13, 2020). All relevant articles were retrieved and evaluated based on pre-selected criteria by two independent researchers. Data was then extracted from variables of interest and conflicts were resolved by a third researcher. The primary outcome was renal function, and the secondary outcomes were proteinuria and hypertension. Results Forty-five studies were included, of which 49% (n = 22) were retrospective and/or 58% (n = 26) were cohort studies. A combined total of 2148 and 885 patients were diagnosed with MCDK or URA, respectively. The proportion of children with worsened renal function at follow-up was found to be 8.4% (95% CI: 5.2%–13.4%). Among the studies reporting renal function as a group mean or median at follow-up, 84% (21/25) had a GFR/CrCl above 90 (mL/min/1.73 m2/ml/min). In terms of secondary outcomes, the proportion of children with proteinuria and hypertension was found to be 10.1% (95% CI: 6.9%–14.6%) and 7.4% (95% CI: 5.0%–10.9%), respectively. Conclusion The risk of developing proteinuria (10.1%), hypertension (7.4%), and/or worsened renal function (8.4%) for children with CFSK as a result of MCDK or URA is low. However, the level of evidence in the literature is weak. Further research is needed to identify the predisposing factors that may differentiate the small subset of children with CSFK at a higher risk of developing adverse renal outcomes.

Introduction Gestational weight gain (GWG) outside of the 2009 Institute of Medicine guidelines may be harmful to women and their fetuses. Prenatal health care providers (HCPs) are important sources of health information, but not all discuss GWG with their patients. The Canadian Obesity Network's 5As (ask, assess, advise, agree, and assist) of Healthy Pregnancy Weight Gain (5As) is a tool developed to help HCPs counsel their patients on GWG. The main objective of this study was to evaluate the impact of the 5As tool on patient perceptions of GWG discussions with their HCP and to identify suggestions to improve the tool. Methods A quasiexperimental study design was conducted whereby HCPs were trained in using the 5As tool (intervention). Patients were then queried at baseline and postintervention using an electronic questionnaire measuring patient-perceived 5As counseling. Inclusion criteria for pregnant women were (1) currently attending their first appointment with participating HCPs, (2) English-speaking, and (3) over 18 years of age. Results One hundred pregnant women (50 baseline, 50 postintervention) and 15 HCPs (11 midwives, 4 obstetricians) participated. Participants receiving care from 5As-trained HCPs reported scores twice as high (P = .047) in being asked about and were approximately 3 times more likely to be advised an exact amount of target weight gain (P = .03). HCPs suggested improving patient handouts and HCP education on GWG guidelines as well as reducing the content presented in the 5As tool. Discussion The 5As Tool is effective at initiating HCP-mediated GWG counseling; further research is needed to examine the usefulness of the 5As in clinical practice throughout the length of a full pregnancy. Whether the uptake of the 5As tool contributes to prenatal behavior change remains to be established. Future steps include modifying the tool based on HCP feedback, the development of novel knowledge translation tools, and improved HCP and patient education.

Cyclooxygenase (COX) contributes to cutaneous vasodilation and sweating responses; however, the mechanisms underpinning these responses remain unknown. We hypothesized that prostaglandin E1 (PGE1) and E2 (PGE2) (COX-derived vasodilator products) directly mediate cutaneous vasodilation and sweating through nitric oxide synthase (NOS)-dependent mechanisms in young adults. Furthermore, we hypothesized that this response is diminished in older adults, since aging attenuates COX-dependent cutaneous vasodilation and sweating. In 9 young (22 ± 5 yr) and 10 older (61 ± 6 yr) adults, cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites receiving incremental doses (0.05, 0.5, 5, 50, 500 μM each for 25 min) of PGE1 or PGE2 with and without coadministration of 10 mM Nω-nitro-l-arginine, a nonspecific NOS inhibitor. Nω-nitro-l-arginine attenuated PGE1-mediated increases in CVC at all concentrations in young adults, whereas it reduced PGE2-mediated increases in CVC at lower concentrations (0.05–0.5 μM) in older adults (all P < 0.05). However, the magnitude of the PGE1- and PGE2-mediated increases in CVC did not differ between groups (all P > 0.05). Neither PGE1 nor PGE2 increased sweat rate at any of the administered concentrations for either the young or older adults (all P > 0.05). We show that although cutaneous vascular responsiveness to PGE1 and PGE2 is similar between young and older adults, the cutaneous vasodilator response is partially mediated through NOS albeit via low-to-high concentrations of PGE1 in young adults and low concentrations of PGE2 in older adults, respectively. We also show that in both young and older adults, PGE1 and PGE2 do not increase sweat rate under normothermic conditions.

KEY POINTS Endothelin-1 (ET-1) is a potent endothelial-derived vasoconstrictor that may modulate cholinergic cutaneous vascular regulation. Endothelin receptors are also expressed on the human eccrine sweat gland, although it remains unclear whether ET-1 modulates cholinergic sweating. We investigated whether ET-1 attenuates cholinergic cutaneous vasodilatation and sweating through a nitric oxide synthase (NOS)-dependent mechanism. Our findings show that ET-1 attenuates methacholine-induced cutaneous vasodilatation through a NOS-independent mechanism. We also demonstrate that ET-1 attenuates cutaneous vasodilatation in response to sodium nitroprusside, suggesting that ET-1 diminishes the dilatation capacity of vascular smooth muscle cells. We show that ET-1 does not modulate methacholine-induced sweating at any of the administered concentrations. Our findings advance our knowledge pertaining to the peripheral control underpinning the regulation of cutaneous blood flow and sweating and infer that ET-1 may attenuate the heat loss responses of cutaneous blood flow, but not sweating. ABSTRACT The present study investigated the effect of endothelin-1 (ET-1) on cholinergic mechanisms of end-organs (i.e. skin blood vessels and sweat glands) for heat dissipation. We evaluated the hypothesis that ET-1 attenuates cholinergic cutaneous vasodilatation and sweating through a nitric oxide synthase (NOS)-dependent mechanism. Cutaneous vascular conductance (CVC) and sweat rate were assessed in three protocols: in Protocol 1 (n = 8), microdialysis sites were perfused with lactated Ringer solution (Control), 40 pm, 4 nm or 400 nm ET-1; in Protocol 2 (n = 11) sites were perfused with lactated Ringer solution (Control), 400 nm ET-1, 10 mm N(G) -nitro-l-arginine (l-NNA; a NOS inhibitor) or a combination of 400 nm ET-1 and 10 mm l-NNA; in Protocol 3 (n = 8), only two sites (Control and 400 nm ET-1) were utilized to assess the influence of ET-1 on the dilatation capacity of vascular smooth muscle cells (sodium nitroprusside; SNP). Methacholine (MCh) was co-administered in a dose-dependent manner (0.0125, 0.25, 5, 100, 2000 mm, each for 25 min) at all skin sites. ET-1 at 400 nm (P 0.05) significantly attenuated increases in CVC in response to 0.25 and 5 mm MCh. A high dose of ET-1 (400 nm) co-infused with l-NNA further attenuated CVC during 0.25, 5 and 100 mm MCh administration relative to the ET-1 site (all P

Background Mobile technology is ubiquitous. Women of childbearing age have embraced health information technology for pregnancy-related counsel as prenatal care provider communication is increasingly scarce and brief. Pregnant women and new mothers place high value in the use of online sources to support their pregnancy information needs. In Canada, over 300,000 women are pregnant annually, with approximately 60% exceeding evidence-based weight gain recommendations. Mobile health (mHealth) tools, such as mobile applications (app), have the potential to reduce excessive gestational weight gain, offering pregnant women trustworthy guidance, ultimately improving the health outcomes of mothers and infants. Therefore, the primary aim of this study was to implement a qualitative, descriptive research design to assess the receptiveness, functionality, and future prospective of the SmartMoms Canada mHealth app. Methods Two focus groups (n = 13) involving both currently pregnant and recently postpartum women were organized on the same day. Focus groups were transcribed verbatim and thematic analysis was undertaken using manual coding and NVivo software. Participants who took part in the focus groups (n = 13) and those who could not attend (n = 4) were asked to complete a Likert-scale survey. All survey responses (n = 17) were analyzed using simple tabulation and percentage analysis. Results Participants were technologically proficient and interacted with several mHealth tools prior to testing the SmartMoms Canada app. Six major themes emerged from thematic analysis: knowledge of pregnancy-specific mHealth services, knowledge and attitudes of weight gain guidelines, weight tracking, strengths of the app, critique and lastly, future suggestions for the app. Conclusions Our thematic analysis found that women positively viewed the future potential of our app and offered constructive feedback to improve the next version. Participants sought more personalization and enhanced app interactivity, along with promotion of overall maternal health including nutrition and mental health, in addition to weight tracking.

Key points In humans in vivo, the mechanisms behind ATP-mediated cutaneous vasodilatation along with whether and how ATP increases sweating remains uncertain. Recent work has implicated nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine in the modulation of cutaneous vasodilatation and sweat production during both local (i.e. localized heating) and whole-body heat stress (i.e. exercise-induced heat stress). We evaluated whether ATP-mediated cutaneous vasodilatation and sweating is mediated via NOS, COX and/or adenosine. We show that in humans in vivo, intradermal administration of ATP induces pronounced vasodilatation which is partially mediated by NOS, but neither COX nor adenosine influences ATP-mediated vasodilatation, and ATP alone does not induce an increase in sweating. These findings advance our basic physiological knowledge regarding control of skin blood flow and sweating, and provide insight into the mechanisms governing thermoeffector activity, which has major implications for whole-body heat exchange and therefore core temperature regulation in humans during heat stress. Abstract In humans in vivo, the mechanisms behind ATP-mediated cutaneous vasodilatation and whether and how ATP increases sweating remain uncertain. We evaluated whether ATP-mediated cutaneous vasodilatation and sweating is mediated via nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine-dependent mechanisms. Cutaneous vascular conductance (CVC, laser Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated at intradermal microdialysis forearm skin sites, each receiving pharmacological agents (two separate protocols). In Protocol 1 (n = 12), sites were perfused with: (1) lactated Ringer solution (Control), (2) 10 mm Nω-nitro-l-arginine (l-NNA, a NOS inhibitor), (3) 10 mm ketorolac (Ketorolac, a COX inhibitor) or (4) a combination of 10 mm l-NNA + 10 mm ketorolac (l-NNA + Ketorolac). In Protocol 2 (n = 8), sites were perfused with: (1) lactated Ringer solution (Control) or (2) 4 mm theophylline (Theophylline, an adenosine receptor inhibitor). At all sites, ATP was simultaneously perfused at 0.12, 1.2, 12, 120 and 1200 nm min−1 (each for 20 min). Relative to CVC at the Control site with ATP infused at 120 nm min−1 (71 ± 9% of max CVC), CVC at the Ketorolac site was comparable (64 ± 13% of max CVC, P = 0.407), but lower at l-NNA (51 ± 15% of max CVC, P = 0.040) and l-NNA + Ketorolac (51 ± 13% of max CVC, P = 0.049) sites. Conversely, across the four skin sites at any other ATP infusion rate (all P > 0.174), no differences in CVC were observed. Theophylline did not influence CVC at any ATP infusion rate (all P > 0.234). Furthermore, no ATP infusion rate elicited an increase in sweating from baseline at any skin site (all P > 0.235). We show that NOS, but neither COX nor adenosine receptors, modulates ATP-mediated cutaneous vasodilatation, whereas ATP does not directly increase sweating.

Local skin heating to 42 °C causes rapid increases in cutaneous perfusion (initial peak), followed by a brief nadir and subsequent sustained elevation (plateau). Several studies have demonstrated that nitric oxide synthase (NOS) largely contributes to the plateau response during local heating. In this study, we tested the hypothesis that voltage-gated potassium (Kv) channels contribute to the plateau of the cutaneous vasodilation during local heating through NOS-dependent mechanisms. Eleven young males (25 ± 4 years) participated in this study wherein cutaneous vascular conductance (CVC) was measured at four intradermal microdialysis sites that were continuously perfused with either 1) lactated Ringer (Control), 2) 10 mM 4-aminopyridine (Kv channel blocker), 3) 10 mM Nω-Nitro-L-arginine (NOS inhibitor), or 4) a combination of 4-aminopyridine and Nω-Nitro-L-arginine. In comparison to the Control site, the inhibition of Kv channels alone attenuated the increase in CVC observed at the initial peak, nadir, and plateau phases measured during local heating; in contrast, the inhibition of NOS alone attenuated the increase in CVC at the nadir and plateau phases only (e.g., plateau response: Control site: 59 ± 5%max, Kv channel blockade site: 49 ± 8%max, NOS inhibition site: 35 ± 11%max, combined inhibition site: 40 ± 12%max). Further, no effect of Kv channel blockade on CVC was measured at any phase of the local heating response when the modulating influence of NOS was simultaneously removed. We show that Kv channels and NOS contribute to the local heating mediated sustained increase (i.e., plateau) in cutaneous vasodilation in an interactive manner. (243/250 words).

We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In 12 adults (25 ± 6 yr), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50 mM sodium nitroprusside (20–25 min). Responses were evaluated at four skin sites treated with either 1) lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were intradermally administered via microdialysis. Relative to the Control site, endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM methacholine, 80 ± 10 vs. 56 ± 15%max, P < 0.01); however, this response was not detected when the Rho kinase inhibitor was simultaneously administered (CVC at 2,000 mM methacholine for Rho kinase inhibitor vs. endothelin-1 + Rho kinase inhibitor sites: 73 ± 9 vs. 72 ± 11%max, P > 0.05). Endothelium-independent vasodilation was attenuated by endothelin-1 compared with the Control site (CVC, 92 ± 13 vs. 70 ± 14%max, P < 0.01). However, in the presence of Rho kinase inhibition, endothelin-1 did not affect endothelium-independent vasodilation (CVC at Rho kinase inhibitor vs. endothelin-1+Rho kinase inhibitor sites: 81 ± 9 vs. 86 ± 10%max, P > 0.05). There was no between-site difference in sweating throughout ( P > 0.05). We show that in young adults, Rho kinase is an important mediator of the endothelin-1-mediated attenuation of endothelium-dependent and -independent cutaneous vasodilation, and that endothelin-1 does not increase sweating.

During exercise, cutaneous vasodilation and sweating responses occur, whereas these responses rapidly decrease during postexercise recovery. We hypothesized that the activation of endothelin A (ETA) receptors, but not endothelin B (ETB) receptors, attenuate cutaneous vasodilation during high-intensity exercise and contribute to the subsequent postexercise suppression of cutaneous vasodilation. We also hypothesized that both receptors increase sweating during and following high-intensity exercise. Eleven men (24 ± 4 yr) performed an intermittent cycling protocol consisting of two 30-min bouts of moderate- (40% V̇o2peak) and high-intensity (75% V̇o2peak) exercise in the heat (35°C), each separated by a 20- and 40-min recovery period, respectively. Cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal microdialysis skin sites: 1) lactated Ringer (control), 2) 500 nM BQ123 (a selective ETA receptor blocker), 3) 300 nM BQ788 (a selective ETB receptor blocker), or 4) a combination of BQ123 + BQ788. There were no between-site differences in CVC during each exercise bout (all P > 0.05); however, CVC following high-intensity exercise was greater at BQ123 (56 ± 9%max) and BQ123 + BQ788 (55 ± 14%max) sites relative to the control site (43 ± 12%max) (all P ≤ 0.05). Sweat rate did not differ between sites throughout the protocol (all P > 0.05). We show that neither ETA nor ETB receptors modulate cutaneous vasodilation and sweating responses during and following moderate- and high-intensity exercise in the heat, with the exception that ETA receptors may partly contribute to the suppression of cutaneous vasodilation following high-intensity exercise.

Endothelin-1 (ET-1) is a potent endothelial-derived vasoconstrictor that may modulate cholinergic cutaneous vascular regulation. Endothelin receptors are also expressed on the human eccrine sweat gland, although it remains unclear whether ET-1 modulates cholinergic sweating. We investigated whether ET-1 attenuates cholinergic cutaneous vasodilatation and sweating through a nitric oxide synthase (NOS)-dependent mechanism. Our findings show that ET-1 attenuates methacholine-induced cutaneous vasodilatation through a NOS-independent mechanism. We also demonstrate that ET-1 attenuates cutaneous vasodilatation in response to sodium nitroprusside, suggesting that ET-1 diminishes the dilatation capacity of vascular smooth muscle cells. We show that ET-1 does not modulate methacholine-induced sweating at any of the administered concentrations. Our findings advance our knowledge pertaining to the peripheral control underpinning the regulation of cutaneous blood flow and sweating and infer that ET-1 may attenuate the heat loss responses of cutaneous blood flow, but not sweating.The present study investigated the effect of endothelin-1 (ET-1) on cholinergic mechanisms of end-organs (i.e. skin blood vessels and sweat glands) for heat dissipation. We evaluated the hypothesis that ET-1 attenuates cholinergic cutaneous vasodilatation and sweating through a nitric oxide synthase (NOS)-dependent mechanism. Cutaneous vascular conductance (CVC) and sweat rate were assessed in three protocols: in Protocol 1 (n = 8), microdialysis sites were perfused with lactated Ringer solution (Control), 40 pm, 4 nm or 400 nm ET-1; in Protocol 2 (n = 11) sites were perfused with lactated Ringer solution (Control), 400 nm ET-1, 10 mm N(G) -nitro-l-arginine (l-NNA; a NOS inhibitor) or a combination of 400 nm ET-1 and 10 mm l-NNA; in Protocol 3 (n = 8), only two sites (Control and 400 nm ET-1) were utilized to assess the influence of ET-1 on the dilatation capacity of vascular smooth muscle cells (sodium nitroprusside; SNP). Methacholine (MCh) was co-administered in a dose-dependent manner (0.0125, 0.25, 5, 100, 2000 mm, each for 25 min) at all skin sites. ET-1 at 400 nm (P 0.05) compared to lower doses (40 pm and 4 nm) (all P 0.05) significantly attenuated increases in CVC in response to 0.25 and 5 mm MCh. A high dose of ET-1 (400 nm) co-infused with l-NNA further attenuated CVC during 0.25, 5 and 100 mm MCh administration relative to the ET-1 site (all P 0.05). Cutaneous vasodilatation in response to SNP was significantly blunted after administration of 400 nm ET-1 (P 0.05). We show that ET-1 attenuates cutaneous vasodilatation through a NOS-independent mechanism, possibly through a vascular smooth muscle cell-dependent mechanism, and methacholine-induced sweating is not altered by ET-1.

Acetylcholine released from cholinergic nerves is a key neurotransmitter contributing to heat stress-induced cutaneous vasodilation and sweating. Given that sympathetic cholinergic nerves also release ATP, ATP may play an important role in modulating cholinergic cutaneous vasodilation and sweating. However, the pattern of response may differ between males and females given reports of sex-related differences in the peripheral mechanisms governing these heat loss responses. Cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated in 17 young adults (8 males, 9 females) at four intradermal microdialysis skin sites continuously perfused with: 1) lactated Ringer (Control), 2) 0.3 mM ATP, 3) 3 mM ATP, or 4) 30 mM ATP. At all skin sites, methacholine was coadministered in a concentration-dependent manner (0.0125, 0.25, 5, 100, 2,000 mM, each for 25 min). In both males and females, CVC was elevated with the lone infusion of 30 mM ATP (both P < 0.05), but not with 0.3 and 3 mM ATP compared with control (all P >0.27). However, 0.3 mM ATP induced a greater increase in CVC compared with control in response to 100 mM methacholine infusion in males ( P < 0.05). In females, 0.3 mM ATP infusion resulted in a lower concentration of methacholine required to elicit a half-maximal response (EC50) ( P < 0.05). In both males and females, methacholine-induced sweating was unaffected by any concentration of ATP (all P > 0.44). We demonstrate that ATP enhances cholinergic cutaneous vasodilation albeit the pattern of response differs between males and females. Furthermore, we show that ATP does not modulate cholinergic sweating.

In humans in vivo, the mechanisms behind ATP-mediated cutaneous vasodilatation along with whether and how ATP increases sweating remains uncertain. Recent work has implicated nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine in the modulation of cutaneous vasodilatation and sweat production during both local (i.e. localized heating) and whole-body heat stress (i.e. exercise-induced heat stress). We evaluated whether ATP-mediated cutaneous vasodilatation and sweating is mediated via NOS, COX and/or adenosine. We show that in humans in vivo, intradermal administration of ATP induces pronounced vasodilatation which is partially mediated by NOS, but neither COX nor adenosine influences ATP-mediated vasodilatation, and ATP alone does not induce an increase in sweating. These findings advance our basic physiological knowledge regarding control of skin blood flow and sweating, and provide insight into the mechanisms governing thermoeffector activity, which has major implications for whole-body heat exchange and therefore core temperature regulation in humans during heat stress.In humans in vivo, the mechanisms behind ATP-mediated cutaneous vasodilatation and whether and how ATP increases sweating remain uncertain. We evaluated whether ATP-mediated cutaneous vasodilatation and sweating is mediated via nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine-dependent mechanisms. Cutaneous vascular conductance (CVC, laser Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated at intradermal microdialysis forearm skin sites, each receiving pharmacological agents (two separate protocols). In Protocol 1 (n = 12), sites were perfused with: (1) lactated Ringer solution (Control), (2) 10 mm N(ω) -nitro-l-arginine (l-NNA, a NOS inhibitor), (3) 10 mm ketorolac (Ketorolac, a COX inhibitor) or (4) a combination of 10 mm l-NNA + 10 mm ketorolac (l-NNA + Ketorolac). In Protocol 2 (n = 8), sites were perfused with: (1) lactated Ringer solution (Control) or (2) 4 mm theophylline (Theophylline, an adenosine receptor inhibitor). At all sites, ATP was simultaneously perfused at 0.12, 1.2, 12, 120 and 1200 nm min(-1) (each for 20 min). Relative to CVC at the Control site with ATP infused at 120 nm min(-1) (71 ± 9% of max CVC), CVC at the Ketorolac site was comparable (64 ± 13% of max CVC, P = 0.407), but lower at l-NNA (51 ± 15% of max CVC, P = 0.040) and l-NNA + Ketorolac (51 ± 13% of max CVC, P = 0.049) sites. Conversely, across the four skin sites at any other ATP infusion rate (all P0.174), no differences in CVC were observed. Theophylline did not influence CVC at any ATP infusion rate (all P0.234). Furthermore, no ATP infusion rate elicited an increase in sweating from baseline at any skin site (all P0.235). We show that NOS, but neither COX nor adenosine receptors, modulates ATP-mediated cutaneous vasodilatation, whereas ATP does not directly increase sweating.