Background
Endothelial dysfunction is one of the earliest vascular changes that occur in the pathogenesis of many cardiovascular diseases (CVD) [
1] including the development of atherosclerosis [
2]. Reversibility of endothelial dysfunction has been demonstrated with various pharmacological interventions such as statins, angiotensin-converting enzyme inhibitors (ACEI), and metformin [
3‐
5]. Microcirculation is said to be the initial site of endothelial damage for women who are at risk of CVD [
6]. Therefore, the assessment of microvascular endothelial function can be utilized as a tool to detect early vascular changes [
7] that may occur due to medical conditions and diseases, or to monitor the response to pharmacological interventions.
According to the Surgeon General’s report in 2010, the exposure to SHS leads to a rapid and sharp increase of endothelial dysfunction and inflammations, which are implicated in acute cardiovascular events and thrombosis [
8]. There were fast accumulating evidences of cardiovascular related parameters which include platelet and endothelial function, arterial stiffness, atherosclerosis, inflammation, oxidative stress, heart rate variability, energy metabolism, and increased infarct size, being delicately responsive to the toxins in SHS [
9]. Early studies have showed that cigarette smoke contains lipophilic substances that are toxic to bovine arterial endothelial cells [
10], and can directly damage the integrity of the endothelial cell layer in man and reduce vasodilator properties in vitro [
11]. Therefore, we hypothesized that there may be differences in microvascular endothelial function among generally healthy non-smoking women who were exposed and non-exposed to SHS. Women with detectable levels of hair nicotine were further divided in those with higher and lower levels of high nicotine; differences in microvascular endothelial function between the three groups were studied.
Discussion
In the present study, there were no significant differences between the three groups for all parameters including microvascular endothelial function.
The endothelium plays a pivotal role in the regulation of vascular tone as well as in the maintenance of vascular integrity. In this respect, nitric oxide (NO) formed by endothelial cells is a crucial importance because it exerts a number of potential protective actions, including vasorelaxation and antithrombotic effects. A condition in which an impaired NO-mediated relaxation is associated with preserved vasodilation to an NO donor is often referred as endothelial dysfunction [
16]. In the present study, we focused on the functional aspects of human peripheral microcirculation and studied its responses to ACh and SNP in the forearm skin among women exposed to SHS. However, exposure to SHS showed no significant differences in the responses of local microcirculation of both ACh and SNP.
It had been reported that acute high dose of SHS exposure for one hour did not damage the microvascular endothelial function among healthy non-smoker women [
17]. Contrary, other findings showed significant reduction of skin blood flow reactivity, indicates the deterioration of peripheral microvascular endothelial function [
18,
19]. We could not find a report on the effects of chronic SHS exposure to microvascular endothelial function. However, the effect of chronic SHS to endothelial function of larger blood vessels has been reported. A study reported that brachial-artery flow-mediated dilatation (FMD) was dose-dependently damaged in women with a history of SHS exposure for more than one hour daily for more than 3 years in comparison with the controls [
20]. Another study stated that, healthy women who are exposed to SHS for more than 1 h daily for more than 10 years showed significant impairment of ACh-induced epicardial coronary artery dilatation, indicating endothelial dysfunction may occur diffusely to the subjects exposed to SHS [
21].
The explanation for the lack of impairment of microvascular endothelial function in the current study remains unclear. Our study was designed to evaluate the effects of chronic exposure to SHS on microvascular endothelial function among healthy women. The intensity of exposure to SHS depends on a large number of variables, such as the exposure time per day, the proximity to the active smokers, the number of active smokers at home or workplace, and the size and ventilation of the rooms where SHS exposure occurs. One possibility to explain the lack of impairment of microvascular endothelial function in the current study may relate to the time of exposure. Our subjects may be exposed to SHS for short periods of time; subjects in previous studies which showed impairment of endothelial function in larger blood vessels were exposed to SHS for at least one hour per day [
20,
21]. Another possibility is, most of our subjects were housewives, and the only active smokers were their husbands. Generally, they were not exposed to SHS while their husbands are at work and their main daily activities were also limited to house chores and close neighbourhood. The SHS exposure that they have might not be adequate to cause significant impairment in their microvascular endothelial function.
The heterogeneity of microvascular and macrovascular endothelial cells in respond to SHS exposure could be another reason why there were no significant changes in microvascular endothelial function in this study. Microvascular and macrovascular endothelial cells have been reported to show different responses to certain medical conditions or interventions. For example, coronary endothelial cells reacted with a decreased secretion of tissue-type plasminogen activator (tPA) and increase plasminogen activator inhibitor type 1 (PAI-1) activity to incubate with oxidized LDL-C, although there was only a minor response by the cardiac microvascular endothelial cells [
22]. Besides, different microvascular and macrovascular responses with different stimulation have been demonstrated previously [
23]. Macrovascular and microvascular perfusion increased significantly using induced hyperaemia at upper and lower arm. However, passive leg raising only changed the macrovascular indices significantly but not the microvascular indices. Moreover, among rheumatoid arthritis patients, there were no association observed between microvascular and macrovascular endothelial-dependent and independent functions [
24], suggesting that microvascular and macrovascular have different regulations of their endothelial function.
Hair nicotine levels of SHS group in our study were comparatively lower compared to a few other previous studies [
14,
25]. This may indicate that the exposure to cigarette smoke in our SHS subjects was relatively low which may contribute to the insignificant effect on microvascular endothelial function. An area that could be studied in the future includes the investigation on women who have heavier exposure to SHS, and confirming this exposure using objective measurement such as hair nicotine levels.
In this study, there were no significant differences in microvascular endothelial function between generally health non-smoking women with higher, lower and non-detected hair nicotine levels. The lack of microvascular endothelial function impairment in this study may be due to insufficient exposure to SHS. The reduction of endothelium-dependent vasodilatation of the skin microvasculature may become visible after many years of exposure, or when exposed to high intensity of SHS.
Competing interests
The authors declare no conflict of interest in this study.
Authors’ contributions
ZS was involved in data collection, analysis, interpretation and manuscript preparation. SHMS, IA and SSMY were involved in data collection, analysis and interpretation. AHGR was involved in data collection, supervised in microvascular endothelial function analysis and manuscript preparation. HMY was involved in the concept and design of the study, data collection and supervised in manuscript preparation. All authors read and approved the final copy.