Peripheral blood flow in menopausal women who have hot flushes and in those who do not.

OBJECTIVE--To compare blood pressure, heart rate, and peripheral vascular responsiveness in menopausal women who have hot flushes and in those who do not, and to assess the effect on these variables of treating women who have hot flushes with oestriol, a natural oestrogen, given vaginally. DESIGN--An open, non-randomised cohort study of flushing and non-flushing menopausal women. A before and after investigation of the effects of vaginal oestriol treatment on the circulation. SETTING--Referral based endocrinology clinic. PATIENTS--88 Consecutive menopausal women, 63 complaining of frequent hot flushes and 25 who had not flushed for at least a year. INTERVENTION--Treatment with vaginal oestriol 0.5 mg at night for six weeks in 18 of the women who had hot flushes. MEASUREMENTS AND MAIN RESULTS--Peripheral blood flow was measured by venous occlusion plethysmography at rest and in response to stressful mental arithmetic and anoxic forearm exercises. Blood flow in the forearm and its variability were significantly higher in flushing than in non-flushing women (4.1 (SD 1.7) and 3.1 (0.9) ml/100 ml tissue/min and 17% and 13% respectively). Blood pressure, heart rate, and blood flow in the hand were, however, similar in the two groups. No difference was found in the peripheral incremental response to either stress or anoxic exercise. Vaginal oestriol significantly lowered forearm blood flow from 4.4 (1.5) to 3.3 (1.1) ml/100 ml tissue/min but dilator responsiveness was unaffected. CONCLUSIONS--The peripheral circulation is different in menopausal women who have hot flushes compared with those who do not, with selective vasodilatation in the forearm. The lowered blood flow in the forearm after vaginal oestriol in flushing women may be relevant to the alleviation of vasomotor symptoms induced by oestrogen treatment.     

Similarities between morphine withdrawal in the rat and the menopausal hot flush

Skin temperature, cardiovascular and neuroendocrine responses to morphine withdrawal in the rat were evaluated in an effort to develop a potential animal model for the menopausal hot flush in women. Morphine dependency was produced by s.c. implantation of pellets containing morphine alkaloid. In response to precipitous, naloxone-induced withdrawal, rats showed surges in tail skin temperature (TST) which were similar in magnitude (4.8 to 7.2 degrees C) and duration (60 to 90 min.) to peripheral skin temperature increases reported during menopausal hot flushes. Additionally, a brief period of accelerated heart rate (59%) and a 9-fold hypersecretion of luteinizing hormone (LH) preceded the TST response to morphine withdrawal. These cardiovascular and neuroendocrine responses are observed to precede or coincide with the menopausal hot flush. Additionally, protracted morphine withdrawal subsequent to abstention, resulted in TST instability characterized by spontaneous, high amplitude TST fluctuations. Thus, the alteration in skin temperature, heart rate and LH secretion during precipitated morphine withdrawal in the rat are similar in magnitude, duration and in their temporal relationship to those observed during the hot flush. These data suggest a possible opioid etiology in this vasomotor disturbance. Acute withdrawal in the morphine addicted rats may serve as an animal model by which to study the neural mechanism underlying the menopausal hot flush.     

An examination of the relationship between sunlight exposure and hot flush in working women

ABSTRACT

We examined whether sunlight affects hot flushes in working menopausal women and explored effect modification by shift work and season. In this prospective cohort study, daily hot flush score (outcome) was measured by the 7-day North Central Cancer Treatment Group Daily Vasomotor Symptoms Diary. Daily duration of sunlight (≥2000 lux) was recorded by the HOBO MX2202 pendant. Both variables were measured in two 7-day data collection phases. T0 data were collected during the Australian Summer (December 2017, January and February 2018); and T1 data were collected in the Australian winter (June, July and August 2018). Linear mixed effects model was used. Shift work and season were both confounders and effect modifiers. To detect a median effect size of R² = 0.2, 34 women were required to achieve an effective sample size of 41. A total of 49 menopausal women were recruited, 11 shift and 38 day workers. Some 13 women had various missing observations. For shift workers, an hour increase in sunlight exposure was associated with a 1.4-point reduction in hot flush score (p = .016). This relationship was not significant for day workers (p = .185). The finding of this study suggests increased sunlight exposure might improve hot flushes in menopausal shift workers who are moderately bothered by hot flushes, but probably not in day workers. The possible role of shift-work associated circadian disruption on estrogen level in regard to elevated intensity and frequency of hot flush in menopausal women is discussed.     

Effect of oral gamolenic acid from evening primrose oil on menopausal flushing.

OBJECTIVE--To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN--Randomised, double blind, placebo controlled study. SETTING--District general hospital and teaching hospital. SUBJECTS--56 menopausal women suffering hot flushes at least three times a day. INTERVENTION--Four capsules twice a day of 500 mg evening primrose oil with 10 mg natural vitamin E or 500 mg liquid paraffin for six months. MAIN OUTCOME MEASURES--Change in the number of hot flushes or sweating episodes a month. RESULTS--56 diaries were analysed, 28 from women taking gamolenic acid and 28 from those taking placebo. Only 18 women given gamolenic acid and 17 given placebo completed the trial. The mean (SE) improvement in the number of flushes in the last available treatment cycle compared with the control cycle was 1.9 (0.4) (P < 0.001) for daytime flushes and 0.7 (0.3) (P < 0.05) for night time flushes in women taking placebo; the corresponding values for women taking gamolenic acid were 0.5 (0.4) and 0.5 (0.3). In women taking gamolenic acid the only significant improvement was a reduction in the maximum number of night time flushes (1.4 (0.6); P < 0.05). CONCLUSION--Gamolenic acid offers no benefit over placebo in treating menopausal flushing.     

Temperature changes suggestive of hot flushes in rhesus monkeys: preliminary observations

To determine if changes in skin temperature known to accompany hot flushes in women also occur in monkeys, temperature recordings were made in three adult rhesus monkeys before and after ovariectomy and in one postmenopausal female. Increases occurred especially on the skin of the ear pinna, with greater frequency following ovariectomy. This animal model may be suitable to investigate the mechanism which causes hot flushes in women.     

Do blood pressure and heart rate responses to perceived stress vary according to endogenous estrogen level in women?

The results of experimental studies suggest that estrogen may blunt blood pressure responses to stress, but increase heart rate responses. We investigated whether within-person associations of perceived stress with blood pressure and heart rate during normal working life in 26 premenopausal and 7 postmenopausal women varied according to endogenous estrogen level. Each woman measured her own blood pressure and heart rate and completed a diary reporting perceived stress levels on six occasions on each of 2 working days. Premenopausal women were assessed once between days 4 and 6 of their menstrual cycle (low estrogen) and again between days 11 and 13 (high estrogen), and urine samples were taken to verify expected variation in estrogen level. Results showed that perceived stress was significantly positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate in the group as a whole. This association did not differ according to menopausal status. There was no difference in the association of perceived stress with SBP or DBP in premenopausal women according to day of assessment, but heart rate reactivity to perceived stress was significantly higher on the high-estrogen day. Our findings thus provide evidence that heart rate responses to perceived stress during everyday working life vary according to estrogen level in premenopausal women, but no evidence that blood pressure responses to stress vary according to endogenous estrogen level in women.     

Plasma homocysteine levels increase in women during psychological stress.

Homocysteine is an amino acid that has been strongly associated with vascular disease. Plasma homocysteine concentrations are known to vary with dietary patterns and to decrease with exogenous estrogen use, but no other behavioral factors have been examined as potential modifiers of this risk factor. Because psychological stress has also been implicated in the development of cardiovascular disease, the purpose of this study was to test the hypothesis that acute psychological stress induces elevations in plasma homocysteine concentrations. A secondary aim was to test potential differences in response between premenopausal and postmenopausal women. Thirty-four healthy women, one-half of whom were naturally postmenopausal with no hormone replacement, participated in this study. The psychological stressors included standard mental arithmetic and speech stressors. Blood samples were taken prior to, during, and after the stressors, and heart rate and blood pressure were also monitored. Results indicated significant elevations in plasma homocysteine during acute psychological stress, with a return to baseline concentrations during recovery. The pattern of findings for blood pressure and heart rate was similar, suggesting that the rise in homocysteine concentrations may have been sympathetically-mediated. No effects of menopausal status or endogenous estrogens were found. The findings provide preliminary evidence that plasma homocysteine may be an important factor in the relationship between psychological stress and risk for heart disease.     

Lipid and lipoprotein profile in menopausal transition. Effects of hormones, age and fat distribution.

The behavior of lipoproteins during the menopausal transition and their relationship with sex hormones and body fat distribution is still unclear. Our aim was to evaluate atherogenic IDL, LDL, Lp(a) and antiatherogenic HDL lipoproteins in four groups of women: premenopausal (n = 20), menopausal transition women with menstrual bleeding (n = 31), menopausal transition women with 3 to 6 months amenorrhea (n = 36), and postmenopausal women (n = 30). We also measured their FSH, LH and estradiol levels along with BMI and waist circumference. Menopausal transition and postmenopausal women showed higher values of waist circumference (p < 0.0032), LDL-cholesterol (p < 0.002), IDL-cholesterol (p < 0.002) and apoprotein B (p < 0.0001) than premenopausal women. Total-cholesterol (p < 0.0001), triglycerides (p < 0.004), IDL-cholesterol and Lp(a) were higher in menopausal transition women with amenorrhea and in postmenopausal women in comparison with premenopausal women. After adjustment according to age and waist circumference, multiple regression analysis showed the increase in total-cholesterol and LDL-cholesterol to be linearly associated to menopausal status and estradiol concentration, whereas Lp(a) was only related to menopausal status. Age was found to be an independent variable in relation to apoprotein B concentration changes. The effect of menopausal status on TG levels did not remain in the model when age, waist and BMI were included (beta = 0.05, p = 0.356). HDL-cholesterol levels were the same in all the groups. Menopause, age and the increase in abdominal fat distribution were three independent and significant factors impairing lipoprotein profiles from the beginning of the menopausal transition.     

更年期潮热与体温调节

由于潮热是更年期女性的最常见和最特异的症状,也是最痛苦的症状之一。潮热主要发生在更年期过渡期的妇女,主要表现为忽冷忽热,其发生严重的影响了更年期妇女的情绪、睡眠及生活质量。但是其发病的病理学机制仍然不清楚。研究表明,潮热的发生与体温调节的异常有关,大多数学者认为潮热发生的机制是体温调节中枢的异常,并通过改变外周和中心体温而实现。因此,本文对潮热时体温调定点,其外周和中心体温的变化情况,作出综述。     

Body temperatures during menopausal hot flashes.

Body temperatures during hot flashes were measured in a menopausal woman. Internal temperatures fell after each flash; lowest: rectal, 35.6 degrees C; vaginal, 35.6 degrees C; tympanic, 35.2 degrees C. Where sweating occurred, the skin temperature fell during the flash and rose after it. Finger and toe temperatures always showed a sharp rise at the onset of a flash with a slower fall after the flash. Only the cheeks showed additional temperature rises; maximum, 0.7 degrees C. The heart accelerated 13% at the onset of the flash but slowed immediately thereafter. The flash interval was sharply demarcated by undulations in the ECG baseline. There was never any premonitory sign of the imminence of a flash. A central excitatory state seemed to build up, perhaps by the accumulation of a chemical compound, but not of heat, which was explosively dischargedmthe thermal distress was probably evoked by vascular warming in the cheeks. Dabbing the malar prominences with cold water brought prompt relief.     

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: A systematic review and meta-analysis

OBJECTIVE: To critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women. DATA SOURCES: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and The Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed. RESULTS: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05). CONCLUSION: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.     

Comparison of the efficacy and tolerability of a new once-a-week matricial estradiol transdermal system (Estrapatch 40 and Estrapatch 60) with a twice week system

OBJECTIVE: To compare the efficacy and tolerability of three transdermal systems (Estrapatch 40, Estrapatch 60 and Oesclim 50). METHODS: Multicentre, randomized, open, 3 parallel group study on 421 postmenopausal women presenting with at least 35 hot flushes in the week preceding inclusion and treated for six 28-day cycles with either Estrapatch 40 (n = 141) or Estrapatch 60 (n = 140) once a week or Oesclim 50 (n = 140) twice a week, associated to oral NETA (Millligynon 2x 0.6 mg tablets daily) from day 15 to day 28. Hot flushes, mastodynia, bleeding, local skin tolerability and adhesiveness were reported on daily cards. Endometrial thickness and estrogens were measured before and after treatment. RESULTS: Efficacy was clearly established for the three devices as early as after one cycle of treatment, with success rates (% of women with a decrease > or = 50% of the number of hot flushes) over 97% from cycle 2. The three treatments were equivalent on this criteria, except at cycle 1 for Estrapatch 40 which was not equivalent to both other treatments. Incidence and severity of mastodynia, bleeding pattern, endometrial thickness and specific estrogen-related adverse events reflected a significant higher estrogenic stimulation with Oesclim 50. Adhesiveness was very satisfactory for the three systems. CONCLUSIONS: Estrapatch 40 and 60 presents a better benefit/risk ratio compared to Oesclim 50. Thus Estrapach 40 appears to be a good choice for a first-line estrogen replacement therapy with the possibility to increase the dose to Estrapatch 60.     

Reproductive status is associated with the severity of fibrosis in women with hepatitis C

Introduction

Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men.

Materials and Methods

A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis.

Results

Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052). Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and early menopausal (P = 0.004) but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001).

Conclusions

The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol/testosterone ratio increase occurs too late to noticeably influence the inflammatory process leading to fibrosis.     

Glucose Tolerance and Weight Loss in Obese Women with Obstructive Sleep Apnea

Background

The association of obstructive sleep apnea (OSA) with glucose intolerance and the beneficial effect of lifestyle intervention have been poorly investigated in women particularly before menopausal status. The study explored 1) whether OSA is associated with impaired glucose homeostasis in obese non diabetic premenopausal and menopausal women and 2) the effects of a 3- month lifestyle intervention on glucose homeostasis in OSA women.

Design and Methods

We consecutively recruited 98 obese women (39 premenopausal) from those referred for a weight loss intervention. Ambulatory nocturnal polysomnography, body composition, oral glucose tolerance test, insulin sensitivity and β cell function were assessed before and after intervention.

Results

41% of premenopausal and 64% of menopausal women had OSA which was associated with worse glucose homeostasis before menopausal status. Mean and minimal nocturnal oxygen saturation (SaO₂) was associated with neck/height ratio (NHR), independently of total and central obesity. Mean and minimal nocturnal SaO₂ and NHR were correlated with insulin sensitivity and fasting glucose. In multivariate analyses, nocturnal mean SaO₂ was negatively and independently correlated with fasting glucose (p<0.0001) and NHR with insulin sensitivity (p<0.0001). In OSA women, the intervention induced a 5% weight reduction and a significant increase in minimal nocturnal SaO₂, insulin sensitivity and β cell function. Changes in fasting glucose and insulin sensitivity were associated with those in minimal nocturnal SaO₂ (p<0.05) and not with weight loss.

Conclusions

In obese women, glucose homeostasis worsens due to nocturnal hypoxia and increased neck circumference through mechanisms partially independent of obesity. OSA is more clearly associated with glucose intolerance in premenopausal than in menopausal women. In OSA women, the improvement of nocturnal hypoxia induced by lifestyle modifications is associated with that of glucose homeostasis.     

Heart rate response to peptide histidine valine in human subjects is not mediated through beta receptors

Peptide histidine valine (PHV) is a 42 amino acid polypeptide closely related to the neuropeptides VIP, PHI and PHM. We have performed a placebo-controlled, double-blind study to assess the hypothesis that the cardiovascular response to PHV infusion may be mediated via the sympathetic nervous system. Four subjects received atenolol or matched placebo 90 min prior to a controlled incremental infusion of PHV, with monitoring of heart rate, blood pressure and skin temperature. Following placebo all subjects showed a dose-related increase in heart rate and skin temperature with no effect on blood pressure during PHV infusion. beta-Blockade had no effect on skin temperature response. Pre-treatment with atenolol reduced the resting blood pressure and the maximum heart rate achieved, but did not affect the percentage increase in heart rate during PHV infusion. This suggests that the action of PHV does not involve beta-receptors. The lack of effect of PHV infusion on blood pressure, despite tachycardia and marked cutaneous vasodilatation, implies that PHV has a different effect on the resistance vessels from that of other peptides such as VIP.     

Physiological reaction of women during exercise and recovery, in a comfortable environment and a hot environment

Physiological reaction and oxygen intake during exercise and recovery were measured in fourteen young female Japanese during the follicular phase of their menstrual cycle at 25 degree C with 50% relative humidity and at 35 degree C with 50% relative humidity. Subjects, clad in bathing suits only, performed a bicycle ergometer exercise at a constant work load of 600 kg . m/min at a cycling rate of 50 rpm for 20 min and recovered while remaining on the bicycle ergometer for 40 min. The mean values of sweat volume and skin temperature were significantly greater at 35 degree C than at 25 degree C. It has been shown that heart rate and rectal temperature during exercise were slightly higher at 35 degree C than at 25 degree C, while those during recovery were significantly higher at 35 degree C than at 25 degree C. Oxygen intake, oxygen debt, and the fall in diastolic blood pressure after exercise were considerably greater at 35 degree C than at 25 degree C. The increase in oxygen intake in a hot environment might result from an increased metabolism due to higher body temperature and increased energy requirement for heat dissipation such as profuse sweating, higher heart rate, and increased ventilatory volume. The increase in oxygen debt in a hot environment might reflect the increased metabolism caused by higher body temperature and the increased production of lactic acid in the working muscle as a result of an insufficient blood supply to the muscle. The increases in sweat volume, oxygen intake during exercise, and oxygen debt in women in a hot environment were considerably smaller than corresponding values for men. The smaller increase in sweat volume in women in a hot environment could reflect a smaller oxygen intake and a more marked dilation of skin vessels in women than in men.     

Elevation of tail skin temperature in ovariectomized rats in relation to menopausal hot flushes

Menopausal hot flushes (HFs), which manifest as an increase in skin temperature, most frequently occur after menopause and cease with the passage of time. We designed this study to elucidate the characteristics of the elevation of tail skin temperature (TST) in ovariectomized (OVX) rats, which is relevant to human symptoms of HFs. First, we measured TST and rectal temperature (RT) and investigated the time course of their changes up to 20 wk after ovariectomy. The TST in OVX rats (28.4 +/- 0.3 degrees C) was significantly (P = 0.0035) elevated from 2 to 7 wk after the ovariectomy compared with that in sham-operated (Sham) rats (27.0 +/- 0.2 degrees C), whereas the RT in OVX rats was elevated from 8 to 20 wk. We next examined the therapeutic effects of estradiol (E(2)) on the elevation of the TST by continuous subcutaneous infusion. E(2) treatment (1.0 microg/day) completely (P = 0.0232) inhibited the elevation of the TST (28.4 +/- 0.3 degrees C for Sham rats, 29.3 +/- 0.3 degrees C for OVX rats, 28.2 +/- 0.4 degrees C for OVX + E(2) 1.0 microg/day rats). These results demonstrated that the elevation of TST in OVX rats was exhibited soon after the estrogen removal and diminished with time and that it was normalized with continuous E(2) replacement. These characteristics are similar to the symptoms of menopausal HFs in women.     

Effect of oestrogen on the sleep,mood, and anxiety of menopausal women.

A double-blind controlled study of the effect of piperazine oestrone sulphate on sleep, depression, anxiety, and hot flushes was performed in 34 perimenopausal women. Half of the patients were given six weeks'' placebo followed by eight weeks'' oestrogen, and half remained on placebo throughout. Sleep was recorded electrophysiologically every week, and mood and anxiety were rated daily by means of visual analogue scales. Hot flushes were counted daily. Observer rating scales of anxiety and depression were complete at intervals. During the first month of active treatment the amount of intervening wakefulness in the first six hours of sleep decreased significantly more in the oestrone group than in those on placebo. Between the baseline period and the second treatment month the oestrone group showed a significantly greater decrease in the total amount of intervening wakefulness and in the frequency of awakenings. Their total amount of rapid eye movement sleep increased. Mood and anxiety improved and the number of hot flushes decreased to a similar degree in both groups. Although oestrogen did reduce the number of episodes of wakefulness in perimenopausal women complaining of insomnia, its effects on their psychological symptoms were little different to those of placebo.     

Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.     

Effect of substance P on cardiovascular and respiratory function in subjects

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.