1 The Mediation Role of Physical Fitness in association between Muscle-

2 Strengthening Physical Activities and its domain with Blood Pressure

3 among Young Adults: Considering Gender and Abnormal Blood
4 Pressure as Moderators, Moderate-Vigorous Physical Activity, Age,
5 Mental Wellbeing, Sleep Behaviour, and Sedentary Behaviour as
6 covariates
7 Mumtaz Maulana Hidayat1, Denny Agustiningsih1, Rahmaningsih Mara Sabirin1,*, Rakhmat
8 Ari Wibowo1

9 1
Department of Physiology, Faculty of Medicine, Public Health and Nursing, Gadjah Mada
10 University, Yogyakarta, Indonesia

11 * Correspondence:
12 Mumtaz Maulana Hidayat
13 [email protected]

14 Keywords: mediation analysis, physical fitness, muscle strengthening, physical activity, blood
15 pressure, young adults

16 Abstract

17 Background : The prevalence of hypertension, especially among young people, continues to increase
18 worldwide and become global burden. This condition is influenced by the lack of physical activity in
19 young people. Although there have been many studies correlate between aerobic physical activity
20 and Muscle-Strengthening Exercise (MSE) with blood pressure, many of them didn’t considered
21 interdependence between them. While fitness components such as muscle strength can be
22 intermediate components between MSE and blood pressure, some studies showing inconsistent
23 results. In addition, various health-related factors that can affect blood pressure conditions such as
24 age, mental health, sleeping behaviour and sedentary behavior are also rarely considered. Moreover,
25 gender and abnormal blood pressure as potential moderators. This research will carry out a
26 mediation-moderation analysis to find out the relationship between muscle strengthening physical
27 activity and blood pressure by considering moderate-vigorous physical activity, age, mental health,
28 sleep behaviour and sedentary behavior. Methods : This study used cross-sectional data from 221
29 young adults who attended a physical activity intervention at a university in Yogyakarta, Indonesia.
30 Muscle Strengthening Activities measured using Indonesian version of Muscle-Strengthening
31 Exercise Questionnaire. Moderate-vigorous physical activities and sitting time, sleep behaviour, and
32 mental well-being were measured using Indonesian Physical Activity, Sedentary Behaviour, and
33 Sleep Questionnaire, Pittsburgh Sleep Quality Index Indonesian Short Version, and Warwick-
34 Edinburgh Mental Wellbeing Scale Indonesian version. Mediation and moderation analyses were
35 conducted using Process Macro model 10 on SPSS 25 to investigate the association of muscle-
36 strengthening activities on blood pressure, with gender and blood pressure as moderator, Handgrip
37 strength measured using Camry dynamometer, Bodyfat percentage measured using Omron BHF375
38 and Cardiorespiratory Fitness (VO2max) measured using the Six Minute Walk Test as mediators, and
39 Moderate-Vigorous Physical Activity, Age, Mental Wellbeing, Sleep Behaviour, and Sedentary
40 Behaviour as covariates. Results : Volume of muscle-strengthening activities in a week have a direct
41 association with blood pressure among male with an effect of 0,0989359 (95% confidence interval
42 0,0046488 to 0,00336478). In addition, weekly volume of free weight domain of muscle
43 strengthening activities have a direct association with blood pressure among male with an effect of
44 0,02548783 (95% confidence interval 0,0076084 to 0,1152689). There is no component of physical
45 fitness that provides a significant mediating effect. Conclusions : This study shows that increased
46 participation in muscle strengthening exercises, especially free weight exercises, could increase
47 blood pressure in male young adults population. The relationship was not significantly mediated by
48 the physical fitness component. Further research is needed to investigate other mechanisms that
49 influence this relationship

50 1 Introduction

51 The prevalence of hypertension, a non-communicable condition, is quite high and is

52 constantly rising. From 1990 to 2019, the number of persons with hypertension more than
53 doubled, from 600 million to more than 1 billion (NCD-Risc, 2021). In just a few years, the
54 prevalence of hypertension among Indonesian adults between the ages of 18 and 24 has nearly
55 doubled. Given that hypertension, especially in young people, can continue to rise and
56 constitute a major financial burden on the world's healthcare system, this should be a serious
57 worry.

58 The high rate of hypertension at a young age is inseparable from the reluctance of young
59 people to do physical activity (Domaradzki et al., 2022). Various studies have shown the
60 benefits of physical activity in maintaining health and controlling non-communicable diseases
61 such as hypertension. Aerobic physical activity and muscle strengthening physical activity are
62 the most commonly associated with blood pressure. Muscle-strengthening physical activities
63 (MSPA) deserve more attention because health surveys in various countries also show that only
64 10-30% of adults do MSPA according to recommendations (Bennie et al., 2020). MSPA are
65 also rarely the focus of promoting physical activity for public health in various countries
66 (Milton et al., 2018).

67 Although there have been many studies looking for a relationship between MSPA and blood
68 pressure, many of them didn't consider the interdependence between them. While fitness
69 components such as muscle strength can be intermediates between MSE and blood pressure,
70 some studies show inconsistent results. MSPA is generally associated with a lower risk of high
71 blood pressure, but several studies have shown that higher blood pressure is associated with
72 higher grip strength through mechanisms that are unclear. Therefore, it is necessary to do an
73 analysis to assess the relationship between various factors (Dong et al., 2016; Blanchard et
74 al., 2018; Taekema et al., 2011).
75 In addition, various health-related factors that can affect blood pressure conditions, such as age,
76 mental health, sleeping behavior, and sedentary behavior are also rarely considered. Moreover,
77 gender and abnormal blood pressure as potential moderators. There are several studies that
78 show differences in response to physical exercise between men and women. Systolic Blood
79 Pressure (SBP) and Diastolic Blood Pressure (DBP) reduction with muscle strengthening
80 exercises differs statistically between men and women (Cornelissen, 2013). Another study
81 showed statistically significantly more pronounced DBP and mean arterial pressure (MAP)
82 reductions from isometric resistance training among males than females (Lopez-Valenciano,
83 2019).

This is a provisional file, not the final typeset article 2

 84 Given that there is still a knowledge gap where there are not many mediation analysis studies
85 that link MSPA and blood pressure with consideration of the interdependence connection
86 between them, this research will carry out a mediation-moderation analysis to find out the
87 relationship between muscle strengthening physical activity and blood pressure by considering
88 moderate-vigorous physical activity, age, mental health, sleep behavior, and sedentary
89 behavior.

90 2. Material and Methods

91

92 2.1 Study Design and Setting

93 We conducted a cross-sectional study taking place at Gadjah Mada University, Yogyakarta,

94 Indonesia. This study was conducted to see the mediating role of physical fitness in the relationship
95 between MSPA and its domain with blood pressure in the young adult population by considering
96 moderate-vigorous physical activity, age, mental health, sleep behavior, and sedentary behavior. Data
97 collection was carried out for 1 month in November-December 2022. The study protocol was
98 approved by the medical and health research ethics committee of the Faculty of Medicine, Public
99 Health, and Nursing at UGM (approval number : KE/FK/1382/EC/2022). This study is a sub-study of
100 a quasi-experimental study entitled "Effectiveness of a virtual challenge with a social component in
101 promoting physical activity, hydration, and fruit consumption among university students.". This study
102 protocol has been registered with the Thai Clinical Registry with the registry number
103 TCTR20230106003.

104

105 2.2 Participants and Sample Size

106 All UGM students, including those pursuing vocational, undergraduate, master's, and doctoral
107 degrees, were qualified to take part in the study. The study excluded participants who had
108 experienced a heart attack within the previous three months, were recovering from surgery, and had
109 physical or mental impairments that precluded them from taking part in all tests. An easy-to-use
110 sampling technique was adopted in this investigation. G*Power analysis was used to calculate the
111 sample size to examine the link between the volume of muscle-strengthening activities and blood
112 pressure (Faul et al., 2007). Using a power of 0.8, an alpha level of 0.05, and an effect size of 0.2,
113 the minimal number of samples is 153.

114 2.3 Effect of Interest

115 This study not only wants to see the direct effect of volume of MSPA on blood pressure but also the
116 indirect effect of various physical fitness components as potential mediators in the relationship
117 between them. This study also wants to see the role of sex and abnormal blood pressure as
118 moderators.

119 2.4 Variables and Causal Assumption

120 We used a modeling framework to examine whether physical fitness mediates the relationship
121 between MSPA volume and blood pressure. MSPA served as independent variable, while systolic
122 blood pressure, diastolic blood pressure, and mean arterial pressure served as dependent variables.

3
123 We also included sedentary behavior, moderate-to-vigorous aerobic physical activity, and sleep
124 behavior as covariates. The model is created with the assumption that independent variables have a
125 significant correlation with the outcome, independent variables have a significant correlation with the
126 mediator, and mediator has a significant correlation with the dependent variable. We investigated the
127 total effect (path c) and direct effect (path c') in the figure above using linear regression with the
128 Hayes model. Path a showed the correlation between the independent variables (MSPA) and the
129 mediators (muscle mass, muscle strength, and CRF). Path b represents the correlation between the
130 mediators (muscle mass, muscle strength, and CRF) and the dependent variable (BP). After
131 adjustment for confounders, the a-b pathway represents the indirect effect of MSPA, which is
132 mediated by muscle mass, muscle strength, nd CRF. The mediated effect is a multiplication of effects
133 a and b. Therefore, the direct effect c’ represents the independent variable’s effect after considering
134 the mediated effect.
135 Diisi gmbar segitiga
136
137
138
139
140
141
142

143 2.5. Outcome Measure

144 2.5.1 Main Outcome : Blood Pressure

145 After a minimum of five minutes of rest, SBP and DBP were assessed in a sitting position using a
146 certified digital instrument (Omron HEM 705CPINT, USA) (15). We measure twice, one minute
147 apart, and then average the two results.Blood pressure measurements were obtained from 8 to 10 a.m.
148 to minimize circadian effects.

149

150 2.5.2 Main Predictor : Volume of Muscle Strength Physical Activity

151 The volume of Muscle Strength Physical Activity (MSPA) for a week was measured by the Muscle
152 Strengthening Exercise Questionnaire (MSEQ), which consists of questions about the duration,
153 intensity, frequency, and domain of muscle strengthening exercises (Shakespear-druery et al,
154 2022). MSPA is expressed in MET-minutes per week.

155 2.5.3 Potential Mediator

156 Muscle Strength

157 Muscle strength was assessed with a Camry handgrip dynamometer (Model EH101). All subjects
158 were asked to sit down while holding the dynamometer in the dominant hand with their arms at a 90
159 degree angle with the body without squeezing the arms against the body. Participants are allowed to
160 do one trial. As in the previous study (Taekama, 2011)(JI, 2018), three trials were performed,

This is a provisional file, not the final typeset article 4

161 resting 60 seconds between measurements on the same hand. The dynamometer was adjusted to the
162 size of the participant's hand before measuring grip strength by turning the adjusting knob right or
163 left to get an ideal grasp. All three scores are averaged for analysis. Grip strength is expressed in
164 kilograms.

165 Muscle Mass

166 Omron Karada Scan HBF 375 Body Fat Composition Monitor Used to measure body weight in
167 kilograms (kg) and percentage of skeletal muscle mass.

168

169 Cardiorespiratory Fitness

170 cardiorespiratory fitness examined by the 6-Minute Walking Test (6MWT) method. The result of the
171 6MWT distance in meters is converted to an estimate of V̇ O2max by the formula (Mänttäri et al,
172 2018). V̇ O2max is expressed in numbers, with units of ml/kg/minute. All physical fitness
173 examinations are carried out in the morning (08.00–12.00 am) to avoid the effects of circadian
174 rhythms.

175

176 2.5.4 Covariate

177 Covariates consist of Moderate-Vigorous physical activity (MVPA), age, mental wellbeing, sleep
178 behavior, and sedentary behavior. MVPA, sedentary behavior, and sleeping habits are measured from
179 questions on a questionnaire that has been tested for reliability and validity in our unpublished study.
180 MVPA is expressed in Met-Minutes per week. Age is expressed in number. Mentall wellbeing is
181 expressed in score (7-35), while sleep behavior is expressed in Score (0-21) and sedentary behaviour
182 expressed in minutes per week.

183 2.6 Statistical Analysis

184 Data will be displayed using descriptive statistics in the form of a mean and standard deviation. The
185 distribution of categorical variables is presented using frequency and proportion. If, in the data
186 normality test, the data is normally distributed, then Pearson correlation is used to see the relationship
187 between volume of muscle strengthening exercises, blood pressure, muscle strength, and percentage
188 of muscle mass. If the data is not normally distributed, then an alternative is using Spearman's
189 correlation. The percentile bootstrapping linear regression using hayes model. Hayes model was used
190 to assess the mediating effect of muscle strength, muscle mass percentage and Cardiorespiratory
191 fitness on the relationship between muscle strengthening exercise volume and blood pressure. All
192 analyses were performed using the SPSS version 25 application with a significance level of 0.05.

193

194 3. Results

195 3.1 participants baseline characteristic

5
196 The data used in this study amounted to 221 respondents. Based on table 1, the majority of subjects
197 were 19 years olded on table 1, the majority of subjects were 19 years old (121 or 54.8%), and the
198 rest were in the age ranges of 18 years and 20-23 years. Based on table 2, the majority of subjects
199 were female, namely 143 people (64.7%) and the remaining 78 men (35.3%).

Cumulative
Age Frequency Percent Valid Percent Percent

Valid 18 39 17.6 17.6 17.6

19 121 54.8 54.8 72.4

20 39 17.6 17.6 90.0

21 14 6.3 6.3 96.4

22 4 1.8 1.8 98.2

23 4 1.8 1.8 100.0

Total 221 100.0 100.0

200 Table 1. Age of Subjects

201

Cumulative
Frequency Percent Valid Percent Percent

Valid 1 78 35.3 35.3 35.3

2 143 64.7 64.7 100.0

Total 221 100.0 100.0

202 Table 2. Sex characteristic

203 Partisipan rata-rata berusia, paling tua berusia, paling muda…… dan kebanyakan berjenis kelamin
204 perempuan. Kebanyakan peserta tergolong under/normo/over weight. Volume MSPA rata2 sebanyak
205 METMinutes per week, paling tinggi sebesar sekian minutes per week, paling rendah sebesar ,..

206 3.2 outcome data

207 Kami menemukan positive/negative correlation antara MSPA dan blood pressure.

This is a provisional file, not the final typeset article 6

208 Melihat analisis mediasi, tidak terdapat efek mediasi baik oleh muscle strength, muscle mass
209 percentage or cardiorespiratory fitness on the relationship between MSPA and blood pressure.
210 Indirect effect dari mediator juga tampak tidak signifikan, sebesar sekian. Terdapat direct effect
211 antara MSPA ke Blood pressure, setelah mempertimbangkan moderator variable yaitu usia dan
212 abnormal blood pressure. Tampak direct effect yang signifikan of MSPA on SBP, DBP.

213

214

215 4. Discussion

216 4.1 Key result

217 4.2 Limitation

218 4.3 Interpretation

219 This study shows statistically that there is a significant positive relationship between MSPA and
220 blood pressure, after entering gender and abnormal blood pressure as moderators. Different results
221 appear when the two variables are not considered, where there is no significant direct effect between
222 MSPA and BP. This shows that sex and abnormal pressure function as moderator variables in the
223 relationship between MSPA and BP.

224 In previous studies that investigated the relationship between muscle strength and BP, there was a
225 positive relationship between MS and BP. However, in the present study, the relationship between
226 MS and BP was not significant. This could be influenced by many things, seeing as the number of
227 samples and the age range used in previous studies were different. However, MSPA has a direct
228 effect on SBP. In the components and domains of MSPA, it turns out that free weight also has a
229 direct effect on SBP in men.

230 However, there was no indirect effect from the mediators studied. This shows that there are other
231 mechanisms or factors other than physical fitness that can mediate the relationship between MSPA
232 and blood pressure. We suspect that there are three things that can explain why there are differences
233 in the effects of MSPA on BP in men and women.

234 First, hormone and autonomic response differences between gender. In women, there is hormone
235 secretion, such as estrogen, which has an effect on nitric oxide synthesis, and provides a relaxing
236 effect on peripheral resistance of blood vessels (Penna et al., 2008). In addition, it is well known that
237 testosterone levels in women are lower than in men. Meanwhile, higher testosterone levels are
238 associated with higher blood pressure (batool, 2016).

239 Then, in resting conditions, young women have lower muscle sympathetic activity to support blood
240 pressure than men. (Christou et al, 2005; schmitt, 2010) This condition is different in older women,
241 especially in menopausal conditions, where there is an accelerated process of sympathetic activity.
242 This explains why, in resting conditions, women's heart rates tend to be lower than men's
243 (Vongpatanasin, 2005)

244 Women typically have a poorer capacity for arterial bed vasoconstriction than males do under
245 specific circumstances following physical activity. Following exercise, women's vascular resistance

7
246 is lower than men's. This could be the reason why women's blood pressure tends to drop more
247 quickly and effectively after exercise than men's does (Bassaero, 2020).

248 Second, differences in metabolism during conditions of abnormal blood pressure. Because of the
249 cross-sectional design of this study, it is not possible to determine whether the association between
250 blood pressure and the amount of muscle-strengthening exercise is causative or allows for a two-way
251 relationship. The increase in blood pressure may be due to adaptation to muscle-building activities, or
252 the individual may already have high blood pressure before beginning of resistance
253 training. Regarding the relationship between muscle strengthening exercises and blood pressure,
254 there is some evidence indicating that there is a disturbance of skeletal muscle oxygenation during
255 exercise in adult subjects with hypertension ( Vongpatanasin) When compared to persons without
256 hypertension, the adult population with hypertension has diminished functional sympatholysis. It has
257 been demonstrated that hypertension people had reduced blood flow and oxygen delivery to
258 functioning skeletal muscles. These effects were assessed in response to lower body negative
259 pressure both at rest and during moderately intense handgrip exercises ( Vongpatanasin)

260 In addition, acute weight training will have an impact on the activation of muscle fibers due to
261 alterations in skeletal muscle metabolism that occur in people with high blood pressure. In
262 individuals with high blood pressure, there is a shift from oxidative metabolism to predominantly
263 glycolytic metabolism under hypoxic conditions in skeletal muscle during weight training This
264 increased use of energy from glycolysis will change the recruitment of type II muscle fibers to be
265 dominant over type I muscle fibers. (Nyberg, gosher, jones, boushel). It is clearly known that the
266 size of type II muscle fibers is relatively larger than type I. This may underlie muscle strengthening
267 exercises associated with increased strength and muscle mass, which can also be associated with high
268 blood pressure.

269 Third, resistance training reduces arterial compliance and exacerbates aortic wave reflection,
270 especially in young subjects. (Miyachi, Cortez) In one study, interventions in young adults showed a
271 20% reduction in central arterial compliance after 2 months of resistance training. The occurrence of
272 arterial stiffness certainly plays a role in increasing blood pressure. Stiffness can occur due to an
273 intermittent increase in arterial blood pressure. This can change the structure of the arteries,
274 especially components that play a role in load-bearing conditions, such as connective tissue collagen
275 and elastin. Although resistant exercise has not been shown to change intima-media thickness, it does
276 have the potential to change the quality of the arterial wall by causing fractures of the elastic
277 lamellae. In addition, high-intensity resistance training is a powerful stimulus to the sympathetic
278 nervous system. Chronic increases in the sympathetic nervous system can decrease arterial
279 compliance through chronic restraint on the arterial wall via the greater sympathetic adrenergic
280 vasoconstrictor tone (Miyachi)

281 Keempat, pada penelitian ini dilakukan pemeriksaan dengan ukuran cuff yang sama. Di sisi lain
282 subjek memiliiki karakteristik antropometrik yang berbeda, termasuk massa otot dan ukuran lengan
283 atas. Hal ini dapat mempengaruhi hasil tekanan darah, dengan asumsi, sesoerang dengan massa otot
284 lengaan atas yg lebih besar ,memiiki resiko untuk ter detect tekanan darah lebih tibggi dengan cuff
285 sama yg dipakai olehh rrsponden lain.

286 Conflict of Interest

287 All financial, commercial or other relationships that might be perceived by the academic community
288 as representing a potential conflict of interest must be disclosed. If no such relationship exists,
289 authors will be asked to confirm the following statement:

This is a provisional file, not the final typeset article 8

290 The authors declare that the research was conducted in the absence of any commercial or financial
291 relationships that could be construed as a potential conflict of interest.

292 Author Contributions

293 The Author Contributions section is mandatory for all articles, including articles by sole authors. If
294 an appropriate statement is not provided on submission, a standard one will be inserted during the
295 production process. The Author Contributions statement must describe the contributions of individual
296 authors referred to by their initials and, in doing so, all authors agree to be accountable for the
297 content of the work. Please see here for full authorship criteria.

298 Funding
299 Details of all funding sources should be provided, including grant numbers if applicable. Please
300 ensure to add all necessary funding information, as after publication this is no longer possible.

301

302

303

304

305 NCD Risk Factor Collaboration (NCD-RisC), 2021. Worldwide trends in hypertension prevalence
306 and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-
307 representative studies with 104 million participants. Lancet. 398(10304):957-980.

308 Domaradzki, J., Koźlenia, D., Popowczak, M., 2022. The Mediation Role of Fatness in Associations
309 between Cardiorespiratory Fitness and Blood Pressure after High-Intensity Interval Training in
310 Adolescents. Int J Environ Res Public Health. 19(3):1698. doi: 10.3390/ijerph19031698.
311 PMID: 35162721; PMCID: PMC8834818.

312

313 Bennie, J.A., Shakespear-Druery, J. dan De Cocker, K., 2020. Muscle-strengthening Exercise
314 Epidemiology: a New Frontier in Chronic Disease Prevention. Sports Med-Open. 6(40).
315 https://doi.org/10.1186/s40798-020-00271.

316 Milton, K., Varela, A.R., Strain, T., Cavill, N., Foster, C., Mutrie, N., 2018. A review of global
317 surveillance on the muscle strengthening and balance elements of physical activity
318 recommendations. J Frailty Sarcopenia Falls, 3(2):114-124.

319 Dong B, Wang Z, Arnold L, Song Y, Wang HJ, Ma J., 2016. The association between blood pressure
320 and grip strength in adolescents: does body mass index matter? Hypertens Res. 39(12):919-
321 925. doi: 10.1038/hr.2016.84. PMID: 27383511.

322 Blanchard, A.R., Taylor, B.A., Thompson, P.D., Lepley, L.K., White, C.M., Corso,
323 L.M., Zaleski, A.L., Pescatello, L.S. 2018. The influence of resting blood pressure on muscle
324 strength in healthy adults. Blood Pressure Monitoring. 23(4):185-190.
325

9
326 Cornelissen VA, Smart NA. Exercise training for blood pressure: a systematic review and
327 meta-analysis. J Am Heart Assoc. 2013 Feb 1;2(1):e004473. doi: 10.1161/JAHA.112.004473.
328 PMID: 23525435; PMCID: PMC3603230.

329 López-Valenciano A, Ruiz-Pérez I, Ayala F, Sánchez-Meca J, Vera-Garcia FJ. Updated

330 systematic review and meta-analysis on the role of isometric resistance training for resting
331 blood pressure management in adults. J Hypertens. 2019 Jul;37(7):1320-1333. doi:
332 10.1097/HJH.0000000000002022. PMID: 30624369.

333 Faul, F.; Erdfelder, E.; Lang, A.-G.; Buchner, A., 2007. G*Power 3: A flexible statistical power
334 analysis program for the social, behavioral, and biomedical sciences. Behavior research
335 methodss. 39:175-191.

336 Shakespear-Druery, J., De Cocker, K., Biddle. S.J.H., Bennie, J. 2022. Muscle-Strengthening
337 Exercise Questionnaire (MSEQ): an assessment of concurrent validity and test-retest reliability.
338 BMJ Open Sport and Exercise Medicine, 14;8(1):e001225.
339 Taekema, D.G., Maier, A.B., Westendorp, R.G., de Craen A.J., 2011. Higher blood pressure is
340 associated with higher handgrip strength in the oldest old. Am J Hypertens. Jan;24(1):83-9.

341 Ji C, Zheng L, Zhang R, Wu Q, Zhao Y. Handgrip strength is positively related to blood

342 pressure and hypertension risk: results from the National Health and nutrition examination
343 survey. Lipids Health Dis. 2018 Apr 17;17(1):86. doi: 10.1186/s12944-018-0734-4. PMID:
344 29665844; PMCID: PMC5904981.

345 Mänttäri A, Suni J, Sievänen H, Husu P, Vähä-Ypyä H, Valkeinen H, Tokola K, Vasankari T. Six-
346 minute walk test: a tool for predicting maximal aerobic power (VO 2 max) in healthy adults.
347 Clin Physiol Funct Imaging. 2018 May 31. doi: 10.1111/cpf.12525. Epub ahead of print. PMID:
348 29851229.

349 Penna C, Tullio F, Merlino A, et al. Postconditioning cardioprotection against infarct size and post-
350 ischemic systolic dysfunction is influenced by gender. Basic Res Cardiol 2009; 104: 390-402

351 Batool AI, Rehman M, Unab S, Naveed N, Arshad M, Jabeen SH, et al. Reproductive
352 Endocrinopathy among Cardiovascular Hypertensive Patients. Saudi Journal of Biomedical Research.
353 2016; 1:13.

354

355 Christou DD, Jones PP, Jordan J, Diedrich A, Robertson D, Seals DR. Women have lower tonic
356 autonomic support of arterial blood pressure and less effective baroreflex buffering than men.
357 Circulation 2005; 111(4): 494-8.

358 [39] Schmitt JA, Joyner MJ, Charkoudian N, Wallin BG, Hart EC. Sex differences in alpha-
359 adrenergic support of blood pressure. Clin Auton Res 2010; 20(4): 271-5.

360 Vongpatanasin W. Autonomic regulation of blood pressure in menopause. Semin Reprod Med 2009;
361 27(4): 338-45.

This is a provisional file, not the final typeset article 10

362 Bassareo PP, Crisafulli A. Gender Differences in Hemodynamic Regulation and
363 Cardiovascular Adaptations to Dynamic Exercise. Curr Cardiol Rev. 2020;16(1):65-72. doi:
364 10.2174/1573403X15666190321141856. PMID: 30907327; PMCID: PMC7393595.

365
366
367 Nyberg M, Gliemann L, Hellsten Y. Vascular function in health, hypertension, and diabetes: effect of
368 physical activity on skeletal muscle microcirculation. Scand J Med Sci Sports. 2015; 25(Suppl 4):60–
369 73.

370
371 Gosker HR, Wouters EF, van der Vusse GJ, Schols AM. Skeletal muscle dysfunction in chronic
372 obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy
373 perspectives. Am J Clin Nutr. 2000; 71:1033–1047. [PubMed: 10799364]

374
375 Jones AM, Ferguson SK, Bailey SJ, Vanhatalo A, Poole DC. Fiber Type-Specific Effects of Dietary
376 Nitrate. Exerc Sport Sci Rev. 2016; 44:53–60. [PubMed: 26829247]

377
378 Boushel R. Muscle metaboreflex control of the circulation during exercise. Acta Physiol(Oxf). 2010;
379 199:367–383. [PubMed: 20353495]

380
381 Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki K, Tabata I, Tanaka H.
382 Unfavorable effects of resistance training on central arterial compliance: a randomized
383 intervention study. Circulation. 2004 Nov 2;110(18):2858-63. doi:
384 10.1161/01.CIR.0000146380.08401.99. Epub 2004 Oct 18. PMID: 15492301.
385
386 Cortez-Cooper MY, DeVan AE, Anton MM, Farrar RP, Beckwith KA, Todd JS, Tanaka H. Effects
387 of high intensity resistance training on arterial stiffness and wave reflection in women. Am J
388 Hypertens. 2005 Jul;18(7):930-4. doi: 10.1016/j.amjhyper.2005.01.008. PMID: 16053989.

11