Cutaneous Vascular Responses Research Articles

Central command and the cutaneous vascular response to isometric exercise in heated humans

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature approximately 1 degrees C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by approximately 12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0+/-9.8 versus 18.6+/-6.4 mmHg, P<0.01), while the elevation of heart rate tended to be lower (19.4+/-10.4 versus 27.4+/-8.1 b.p.m., P=0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans.

Control Of Cutaneous Vascular Conductance During Presyncope In The Heat Stressed Human

Pronounced reductions in peripheral vascular resistance occur upon the onset of presyncope during orthostatic stress. This response contributes to the rapid fall in blood pressure associated with presyncopal symptoms. During pronounced orthostatic stress in the heat stressed individuals, cutaneous vascular conductance (CVC) remains above pre-heat stress baseline. It is unknown whether CVC increases at presyncope during combined heat and orthostatic stress. PURPOSE This project tested the hypothesis that CVC increases during orthostatic-induced presyncope in heat stressed individuals. METHODS Five healthy subjects experienced presyncope during lower body negative pressure while heat stressed (via water perfused suit). Forearm skin blood flow (SkBF), arterial blood pressure (catheterization of brachial artery), and heart rate (HR) were continuously measured. CVC was calculated from the ratio SkBF and mean arterial pressure (MAP) 1 min prior to presyncope and at presyncope. RESULTS Heat stress significantly increased skin and internal temperatures, CVC, and HR, without changing MAP. At presyncope HR (82±18 to 65±12 bpm; P=0.02) and MAP (71±11 to 54±4 mmHg; P=0.05) were reduced relative to the period prior to presyncope. However, there was no difference in CVC between these time points (0.88±0.22 to 0.91±0.31 AU/mmHg; P=0.81) despite a decrease in SkBF (62.3±16.2 to 48.6±15.2 AU; p < 0.01). CONCLUSIONS These finding do not support the hypothesis that CVC increases during presyncope, thereby suggesting that cutaneous vascular responses do not contribute to the reduction in blood pressure during vasovagal syncope in heat stressed subjects. Work supported by NIH HL67422 and HL61388

Control Of Cutaneous Vascular Conductance During Presyncope In The Heat Stressed Human

Pronounced reductions in peripheral vascular resistance occur upon the onset of presyncope during orthostatic stress. This response contributes to the rapid fall in blood pressure associated with presyncopal symptoms. During pronounced orthostatic stress in the heat stressed individuals, cutaneous vascular conductance (CVC) remains above pre-heat stress baseline. It is unknown whether CVC increases at presyncope during combined heat and orthostatic stress. PURPOSE This project tested the hypothesis that CVC increases during orthostatic-induced presyncope in heat stressed individuals. METHODS Five healthy subjects experienced presyncope during lower body negative pressure while heat stressed (via water perfused suit). Forearm skin blood flow (SkBF), arterial blood pressure (catheterization of brachial artery), and heart rate (HR) were continuously measured. CVC was calculated from the ratio SkBF and mean arterial pressure (MAP) 1 min prior to presyncope and at presyncope. RESULTS Heat stress significantly increased skin and internal temperatures, CVC, and HR, without changing MAP. At presyncope HR (82±18 to 65±12 bpm; P=0.02) and MAP (71±11 to 54±4 mmHg; P=0.05) were reduced relative to the period prior to presyncope. However, there was no difference in CVC between these time points (0.88±0.22 to 0.91±0.31 AU/mmHg; P=0.81) despite a decrease in SkBF (62.3±16.2 to 48.6±15.2 AU; p < 0.01). CONCLUSIONS These finding do not support the hypothesis that CVC increases during presyncope, thereby suggesting that cutaneous vascular responses do not contribute to the reduction in blood pressure during vasovagal syncope in heat stressed subjects. Work supported by NIH HL67422 and HL61388

Cutaneous vascular responses to isometric handgrip exercise during local heating and hyperthermia

The dramatic increase in skin blood flow and sweating observed during heat stress is mediated by poorly understood sympathetic cholinergic mechanisms. One theory suggests that a single sympathetic cholinergic nerve mediates cutaneous active vasodilation (AVD) and sweating via cotransmission of separate neurotransmitters, because AVD and sweating track temporally and directionally when activated during passive whole body heat stress. It has also been suggested that these responses are regulated independently, because cutaneous vascular conductance (CVC) has been shown to decrease, whereas sweat rate increases, during combined hyperthermia and isometric handgrip exercise. We tested the hypothesis that CVC decreases during isometric handgrip exercise if skin blood flow is elevated using local heating to levels similar to that induced by pronounced hyperthermia but that this does not occur at lower levels of skin blood flow. Subjects performed isometric handgrip exercise as CVC was elevated at selected sites to varying levels by local heating (which is independent of AVD) in thermoneutral and hyperthermic conditions. During thermoneutral isometric handgrip exercise, CVC decreased at sites in which blood flow was significantly elevated before exercise (-6.5 +/- 1.8% of maximal CVC at 41 degrees C and -10.5 +/- 2.0% of maximal CVC at 43 degrees C; P < 0.05 vs. preexercise). During isometric handgrip exercise in the hyperthermic condition, an observed decrease in CVC was associated with the level of CVC before exercise. Taken together, these findings argue against withdrawal of AVD to explain the decrease in CVC observed during isometric handgrip exercise in hyperthermic conditions.

Commentary to Accompany ???Influence of Progestin Bioactivity on Cutaneous Vascular Responses to Passive Heating???

Commentary to Accompany ???Influence of Progestin Bioactivity on Cutaneous Vascular Responses to Passive Heating???

Influence of Progestin Bioactivity on Cutaneous Vascular Responses to Passive Heating

Oral contraceptives influence the regulation of cutaneous vascular tone, and both estrogen and progesterone have been shown to affect nitric oxide (NO)-mediated vasodilation. We tested the hypothesis that cutaneous vascular conductance (CVC) during passive heating would be lower in women taking oral contraceptives with higher progestational bioactivity compared with those taking oral contraceptives with lower progestational bioactivity. We further hypothesized that this difference could be attributed to the relative degree of NO-dependent vasodilation. Fourteen women (20.3 +/- 0.3 yr) taking combined oral contraceptives (low progestin: 6 subjects, high progestin: 8 subjects) participated in a whole-body heating protocol and were tested during the end of active and placebo pill phases. Red blood cell (RBC) flux was measured by laser-Doppler flowmetry at a control microdialysis site (Ringer's solution) and an experimental site where NO-synthase (NOS) was inhibited (10 mM L-NAME). CVC was calculated as RBC flux/MAP. Baseline oral temperature (Tor) was significantly higher during the active pill phase for all subjects (active: 36.8 +/- 0.1 degrees C; placebo: 36.6 +/- 0.1 degrees C) (P = 0.02) but was not affected by progestational bioactivity. CVC at the control site during heating did not differ between low and high progestin users during either phase of oral contraceptive use. However, CVC in the NOS inhibited site was diminished during both phases of oral contraceptive use in the low progestin group at a given change in Tor (active: DeltaT(or) of 0.6-1.0 degrees C, placebo: DeltaT(or) of 0.8-1.0 degrees C) (P < 0.05). (DeltaT(or) 1.0 degree C: active: 30.86 vs 46.56%CVC(max); placebo: 26.29 vs 49.22% CVC(max)) (P < 0.05). Progestational activity in oral contraceptives may alter the mechanisms by which skin blood flow increases during passive heating via NO-dependent cutaneous active vasodilation.

Regulation of Wheal and Flare by Tea Tree Oil: Complementary Human and Rodent Studies

When applied 20 min after injection of histamine into human forearm skin, tea tree oil (TTO) reduces the developing cutaneous vascular response. In this study, the effect of TTO on inflammatory microvascular changes was dissected at the base of an experimental blister on rat skin. 1,8-Cineole, representing 2% of TTO, reduced vascular changes induced by sensory neuropeptides released when the distal portion of a cut sciatic nerve was electrically stimulated. The pre-terminal modulatory effect of 1,8-Cineole was confirmed in tests in sensory-denervated rats. Terpinen-4-ol (approximately 40% TTO) reduced substance P-induced microvascular changes and protein extravasation by a direct nitric oxide-mediated effect on the microvasculature, without sensory nerve involvement. alpha-Terpineol (3% of TTO) regulated both pre- and post-sensory nerve terminals. In human skin, terpinen-4-ol applied 10 min after histamine injection, but not alpha-terpineol or 1,8-cineole, regulated the developing wheal and flare suggesting that the histamine-induced responses in humans (at the dose used in this study, 50 microL of 330 microM histamine) are in large part determined by histamine directly affecting the vasculature via post-terminal-mediated events. The underlying strength of these studies is the use of a well-established rat physiologic model to differentiate the mechanism of regulation of microvascular changes by modulatory agents.

Human cutaneous vascular responses to whole-body tilting, Gz centrifugation, and LBNP.

We hypothesized that gravitational stimuli elicit cardiovascular responses in the following order with gravitational stress equalized at the level of the feet, from lowest to highest response: short-(SAC) and long-arm centrifugation (LAC), tilt, and lower body negative pressure (LBNP). Up to 15 healthy subjects underwent graded application of the four stimuli. Laser-Doppler flowmetry measured regional skin blood flow. At 0.6 G(z) (60 mmHg LBNP), tilt and LBNP similarly reduced leg skin blood flow to approximately 36% of supine baseline levels. Flow increased back toward baseline levels at 80-100 mmHg LBNP yet remained stable during 0.8-1.0 G(z) tilt. Centrifugation usually produced less leg vasoconstriction than tilt or LBNP. Surprisingly, SAC and LAC did not differ significantly. Thigh responses were less definitive than leg responses. No gravitational vasoconstriction occurred in the neck. All conditions except SAC increased heart rate, according to our hypothesized order. LBNP may be a more effective and practical means of simulating cardiovascular effects of gravity than centrifugation.

Enhanced cutaneous vascular response in AD subjects under donepezil therapy

Objective: Abnormal cutaneous vasodilatory responses to the iontophoresis of vasodilators were previously observed in Alzheimer’s disease (AD). We sought to replicate these observations and further identify peripheral vascular components of AD pathology. Methods: Methacholine chloride (MCh), acetylcholine chloride (ACh), and sodium nitroprusside (SNP) were applied iontophoretically to forearm skin. Laser Doppler imaging of treated areas yielded total perfusion response values. Results: Response to MCh was enhanced 78% ( P=0.003) in AD subjects under therapy with the acetylcholinesterase inhibitor (AChEI) donepezil ( N=9), relative to age- and sex-matched controls ( N=12). Significant increases in perfusion were also observed after application of ACh (68%, P=0.03) and SNP (46%, P=0.04). Conclusions: A previous study reported attenuated response to ACh in AD. Paradoxically, we observed a substantially enhanced response that is likely a consequence of donepezil therapy. The increased response to the endothelium-independent vasodilator SNP indicates improved general vasodilatory response, perhaps due to preservation of endogenous ACh by donepezil. Cerebral perfusion in response to functional activation may be improved in this way, suggesting a secondary therapeutic mode of donepezil.

Monitoring blood glucose changes in cutaneous tissue by temperature-modulated localized reflectance measurements.

Most proposed noninvasive methods for glucose measurements do not consider the physiologic response of the body to changes in glucose concentration. Rather than consider the body as an inert matrix for the purpose of glucose measurement, we exploited the possibility that noninvasive measurements of glucose can be approached by investigating their effects on the skin's thermo-optical response. Glucose concentrations in humans were correlated with temperature-modulated localized reflectance signals at wavelengths between 590 and 935 nm, which do not correspond to any near-infrared glucose absorption wavelengths. Optical signal was collected while skin temperature was modulated between 22 and 38 degrees C over 2 h to generate a periodic set of cutaneous vasoconstricting and vasodilating events, as well as a periodic change in skin light scattering. The method was tested in a series of modified meal tolerance tests involving carbohydrate-rich meals and no-meal or high-protein/no-carbohydrate meals. The optical data correlated with glucose values. Changes in glucose concentrations resulting from a carbohydrate-rich meal were predicted with a model based on a carbohydrate-meal calibration run. For diabetic individuals, glucose concentrations were predicted with a standard error of prediction <1.5 mmol/L and a prediction correlation coefficient 0.73 in 80% of the cases. There were run-to-run differences in predicted glucose concentrations. Non-carbohydrate meals showed a high degree of scatter when predicted by a carbohydrate meal calibration model. Blood glucose concentrations alter thermally modulated optical signals, presumably through physiologic and physical effects. Temperature changes drive cutaneous vascular and refractive index responses in a way that mimics the effect of changes in glucose concentration. Run-to-run differences are attributable to site-to-site structural differences.

Different patterns of parasympathetic activation in uni- and bilateral migraineurs.

Several lines of evidence support involvement of the parasympathetic system in migraine: (i) migraine-associated symptoms, such as exaggerated facial flushing, lacrimation and rhinorrhea; (ii) increased levels of cranial venous vasoactive intestinal peptide in migraineurs during attacks; and (iii) reports of migraine pain alleviation by intranasal instillation of lidocaine, which can block some of the parasympathetic outflow to the cranium. This study assessed cranial parasympathetic function in migraineurs in between attacks, assuming that abnormal function might imply involvement of the parasympathetics in migraine pathogenesis. We tested 39 female migraineurs outside attacks, of whom 11 had bilateral pain, 20 unilateral at a specific side and eight alternating unilateral head pain, and 16 controls. The trigemino-parasympathetic reflex was studied, using soapy and saline eye drops for stimulation of the afferent limb of the reflex arch, and cutaneous vascular response at the forehead for the efferent limb. The latter was recorded by photoplethysmography on both sides of the forehead. We found no difference in vasodilatation between migraineurs as a group and controls (83.7 +/- 6.5% and 80.8 +/- 7.6%, respectively, not significant). However, when analysing data by the site of pain, we found that those with bilateral pain had the largest vasodilatation response (141.6 +/- 16.2%, P < 0.05 versus controls, analysis of varance, post hoc Tukey-Kramer HSD), while those with unilateral pain had the least vasodilatation (45.5 +/- 3.3%, P < 0.05). The response of patients with alternating pain (97.2 +/- 12.6%) did not differ from controls. It is concluded that cranial parasympathetic function does differ among patients with various migraine types at rest. Based on the understanding of dysfunctional brainstem pain modulation in migraine, we suggest a model of within-brainstem interaction between the two locus coeruleus nuclei, which are involved in control of pain and cranial parasympathetic outflow. The model assumes various levels of inhibitory inter-relationships between these two nuclei; diminution or absence of the normal reciprocal inhibitory relationships between them may underlie the augmented cranial parasympathetic response in bilateral migraineurs, while an excess of reciprocal inhibitory relationship between them may underlie the diminished cranial parasympathetic response in unilateral migraineurs. These findings might help in clarifying inter-relationships between brainstem nuclei in the context of migraine pathogenesis.

Effects of Aspirin on Cutaneous Vascular Responses to Warming and Cooling in Primary Raynaud's Disease

Effects of Aspirin on Cutaneous Vascular Responses to Warming and Cooling in Primary Raynaud's Disease

Effects of Aspirin and Vitamin C on Cutaneous Vascular Responses Evoked by Acetylcholine (Ach) in Young Male Subjects

Effects of Aspirin and Vitamin C on Cutaneous Vascular Responses Evoked by Acetylcholine (Ach) in Young Male Subjects

Cutaneous vascular responses evoked by noxious stimulation in rats with the spinal nerve ligation-induced model of neuropathy

Antidromic activation of nociceptive nerve fibres innervating the skin produces an axon reflex that involves extravasation and vasodilation of cutaneous blood vessels. We determined whether the axon reflex of the hindlimb skin is influenced by an experimental model of neuropathy induced by unilateral ligation of spinal nerves L 5 and L 6 in the rat. Ligation of spinal nerves induced symptoms mimicking tactile allodynia, as indicated by a marked decrease of the hindlimb withdrawal threshold to mechanical stimulation. The axon reflex induced by antidromic electrical stimulation of nociceptive fibres innervating the plantar skin ipsilateral to the ligation was attenuated according to determination of extravasation response and blood flow response. Lidocaine block or transection of the sciatic nerve of the neuropathic limb did not induce any change in basal blood flow of the plantar skin. The results indicate that ligation of spinal nerves induces an attenuation of the axon reflex. This attenuation reflects a decrease in the efferent function of primary afferent nociceptors innervating the hypersensitive skin of the hindpaw. The attenuation of antidromically-induced vascular responses was not caused by overriding sympathetic activity, as indicated by lack of blood flow effects by lidocaine blocks or a transection of the sciatic nerve.

Effects of chronic sympathectomy on locally mediated cutaneous vasodilation in humans.

In human skin, the vasodilator response to local heating includes a sensory nerve-dependent peak followed by a nadir and then a slower, nitric oxide-mediated, endothelium-dependent vasodilation. To investigate whether chronic sympathectomy diminishes this endothelium-dependent vasodilation, we studied individuals who had previously undergone surgical T(2) sympathectomy (n = 9) and a group of healthy controls (n = 8). We assessed the cutaneous vascular response (laser-Doppler) to 30 min of local warming to 42.5 degrees C on the ventral forearm (no sympathetic innervation) and the lower legs (sympathetic nerves intact). Lower body negative pressure (LBNP) was measured to confirm sympathetic denervation. During local warming in sympathectomized individuals, vascular conductance reached an initial peak at both sites [achieving 1.73 +/- 0.22 laser-Doppler units (LDU)/mmHg in the forearm and 1.92 +/- 0.21 LDU/mmHg in the leg]. It then decreased to a nadir in the innervated leg [to 1.77 +/- 0.23 LDU/mmHg (P < 0.05)] but not in the sympathectomized arm (1.69 +/- 0.21 LDU/mmHg; P > 0.10). The maximal vasodilation seen during the slower phase was not different between limbs or between groups. Furthermore, LBNP caused a 44% reduction in forearm vascular conductance (FVC) in control subjects, but FVC did not decrease significantly in sympathectomized individuals, confirming sympathetic denervation. These data indicate that endothelial function in human skin is largely preserved after sympathectomy. The altered pattern of the response suggests that the nitric oxide-dependent portion may be accelerated in sympathectomized limbs.

Reaction of Cutaneous Blood Vessels to Successive Insults: Repeated Intradermal Histamine Challenge on Normal and Irritated Human Skin

Background: Histamine, a major mediator in endogenous and exogenous skin disorders, has been extensively investigated. Many experiments concern external provocation, yet the sequence of events as well as the influence of timing of the provocating factors require clarification. Objective: To document cutaneous reactivity to histamine rechallenge at different time points, as well as the response of irritated skin (irritant dermatitis) to histamine. Methods: Histamine was intradermally administered on the upper back of 20 volunteers at different time points to 3 sites and following SLS-induced irritant dermatitis to another site. The cutaneous vascular response was measured by laser Doppler flowmetry. Results: The response to a second prick when the first prick response had decayed to half its peak was significantly higher than all the other responses that resulted from a second prick (p < 0.01). The other responses did not significantly differ from each other or from the first prick response. When the histamine prick was performed over a 24-hour SLS patch, the response was greater than at all other sites (p < 0.01). Conclusion: An excitation state, at which the skin readily reacted to the second insult, may underlie the augmentation of the response to a histamine prick over the irritated skin. Irritation modulates cytokines, which may be the mechanism by which the response to histamine administration is enhanced. Tachyphylaxis did not occur at the time points tested, but may occur at longer intervals, necessitating further investigation.

Cutaneous vascular response and thermoregulation in individuals with paraplegia during sustained arm-cranking exercise.

This study investigated whether a 60-minute arm-cranking exercise at 50% of the individual maximal power output would increase lower limb skin blood flow (laser Doppler flowmetry) in individuals with high-level (T5-T9; n = 6) and low-level paraplegia (T10-T12; n = 6), compared to 6 able-bodied controls. Significant (P < 0.05) group by time interactions (two-way repeated measures ANOVA) were found for leg cutaneous vascular conductance, leg skin temperature and esophageal temperature. Cutaneous vascular conductance increased to a peak of approximately 180% of pre-exercise rest in both paraplegic groups and to -436% in the control group, with differences after 15, 30, 45 and 60 minutes of exercise. Leg skin temperature increased by approximately 0.3 C in individuals with paraplegia and decreased by approximately 2.0 C in able-bodied. Esophageal temperature increases at the end of exercise were higher in individuals with paraplegia (approximately 0.9 C) than in able-bodied subjects (approximately 0.5 C). Heart rate was higher in the paraplegic groups than in able-bodied, whilst stroke volume and cardiac output were not different (impedance cardiography). The data suggest that lesion level had no influence on the results. These findings indicate that there is no excessive shunting of blood to the skin of the lower limbs of individuals with paraplegia during sustained exercise.

Investigation of cutaneous microvascular activity and flare response in patients with fibromyalgia syndrome.

To assess microvascular activity in the skin of patients with fibromyalgia syndrome (FMS) as compared with normal controls. Fifteen patients, who fulfilled the American College of Rheumatology criteria for FMS, and 15 age- and sex-matched healthy controls, were studied. The microvascular activity of the skin overlying the trapezius muscle was quantified using iontophoresis of acetylcholine as an endothelial-dependent vasodilator and sodium nitroprusside as an endothelial-independent vasodilator. We also studied the flare response by iontophoresing acetylcholine continuously for 10 min to stimulate a ring of nociceptor c-fibre endings in the skin. There was no significant difference in cutaneous vascular responses to short-duration iontophoresis of acetylcholine and sodium nitroprusside at the three different doses used. The area under the curve (AUC) (mean+/-s.e.m.) for acetylcholine baseline, 20, 40, and 80 s were 6+/-0.7, 23+/-6, 45+/-7 and 66+/-10 AU for patients and 11+/-4, 24+/-3, 49+/-7 and 62+/-12 AU for controls, respectively (P=0.2, 0.9, 0.7, 0.8, respectively). The corresponding figures for sodium nitroprusside were 5+/-1, 18+/-7, 51+/-14 and 68+/-14 AU for patients and 8+/-3, 13+/-2, 39+/-5 and 61+/-9 AU for controls, respectively (P=0.2, 0.5, 0.4, 0.7, respectively). There was also no significant difference in the flare response in patients with FMS as compared with control subjects (119+/-15 and 131+/-13 AU, respectively; P=0.57). There are no significant differences in cutaneous microvascular reactivity between patients with FMS and control subjects.

The influence of topical capsaicin on the local thermal control of skin blood flow in humans.

To test whether heat-sensitive receptors participate in the cutaneous vascular responses to direct heating, we monitored skin blood flow (SkBF; laser Doppler flowmetry) where the sensation of heat was induced either by local warming (T(Loc); Peltier cooling/heating unit) or by both direct warming and chemical stimulation of heat-sensitive nociceptors (capsaicin). In part I, topical capsaicin (0.075 or 0.025%) was applied to 12 cm(2) of skin 1 h before stepwise local warming of untreated and capsaicin-treated forearm skin. Pretreatment with 0.075% capsaicin cream shifted the SkBF/T(Loc) relationship to lower temperatures by an average of 6 +/- 0.8 degrees C (P < 0.05). In part II, we used a combination of topical capsaicin (0.025%) and local warming to evoke thermal sensation at one site and only local warming to evoke thermal sensation at a separate site. Cutaneous vasomotor responses were compared when the temperatures at these two sites were perceived to be the same. SkBF differed significantly between capsaicin and control sites when compared on the basis of actual temperatures, but that difference became insignificant when compared on the basis of the perceived temperatures. These data suggest heat-sensitive nociceptors are important in the cutaneous vasodilator response to local skin warming.

Effect of neuropeptide Y on the sympathetic contraction of the rabbit central ear artery during cooling.

In order to analyse the effect of neuropeptide Y (NPY) on the cutaneous vascular response to sympathetic nerve stimulation during cooling, the isometric response of isolated 2-mm segments of the rabbit central ear (cutaneous) artery was recorded at 37 degrees C and during cooling (30 degrees C). Electrical field stimulation (4-16 Hz) at 37 degrees C produced a frequency-dependent contraction, which was reduced during cooling (45% for 16 Hz) and potentiated by NPY (10(-8), 3x10(-8) and 10(-7) M), this potentiation being greater at 30 degrees C than at 37 degrees C. The NPY-induced potentiation of the contraction elicited by electrical field stimulation (8 Hz) was abolished by an antagonist of Y1 subtype NPY receptors, BIBP3226 (10(-6) M), at 37 degrees C and 30 degrees C, reduced by phentolamine (10(-6) M) at 30 degrees C but not at 37 degrees C, was not modified by the purinoceptor antagonist PPADS (3x10(-5) M) and was reduced by application of both phentolamine and PPADS at both temperatures. Both NiCl2 (10(-3) M) and verapamil (10(-5) M) abolished the potentiating effect of NPY at 37 degrees C and reduced it at 30 degrees C. Neither application of an inhibitor of nitric oxide synthesis, L-Nomega-nitro-arginine (L-NOARG, 10(-4) M), nor endothelium removal modified the potentiating effect of NPY at 37 degrees C or 30 degrees C. NPY (10(-8), 3x10(-8) and 10(-7) M) potentiated in a concentration-dependent way the arterial contraction in response to exogenous noradrenaline (10(-8)-10(-4) M) at 30 degrees C but not at 37 degrees C, and it increased the response to ATP (10(-4)-10(-2) M) at both temperatures. Therefore, in cutaneous (ear) arteries: (1) NPY potentiates the sympathetic response at 37 degrees C and at 30 degrees C, (2) this potentiating effect of NPY was more marked at 30 degrees C than at 37 degrees C, probably because of greater potentiation of the alpha-adrenoceptor response during cooling, and (3) the potentiating effect of NPY at both temperatures is mediated by NPY receptors of the Y1 subtype, is dependent of Ca2+ channels and is independent of the release of endothelial nitric oxide.