Ascorbic Acid Prevents Vascular Endothelial Dysfunction Induced by Electronic Hookah (Waterpipe) Vaping

Mary Rezk-Hanna, Douglas R Seals, Matthew J Rossman, Rajat Gupta, Charlie O Nettle, Angelica Means, Daniel Dobrin, Chiao-Wei Cheng, Mary-Lynn Brecht, Zab Mosenifar, Jesus A Araujo, Neal L Benowitz, Mary Rezk-Hanna, Douglas R Seals, Matthew J Rossman, Rajat Gupta, Charlie O Nettle, Angelica Means, Daniel Dobrin, Chiao-Wei Cheng, Mary-Lynn Brecht, Zab Mosenifar, Jesus A Araujo, Neal L Benowitz

Abstract

Background Electronic hookah (e-hookah) vaping has increased in popularity among youth, who endorse unsubstantiated claims that flavored aerosol is detoxified as it passes through water. However, e-hookahs deliver nicotine by creating an aerosol of fine and ultrafine particles and other oxidants that may reduce the bioavailability of nitric oxide and impair endothelial function secondary to formation of oxygen-derived free radicals. Methods and Results We examined the acute effects of e-hookah vaping on endothelial function, and the extent to which increased oxidative stress contributes to the vaping-induced vascular impairment. Twenty-six healthy young adult habitual hookah smokers were invited to vape a 30-minute e-hookah session to evaluate the impact on endothelial function measured by brachial artery flow-mediated dilation (FMD). To test for oxidative stress mediation, plasma total antioxidant capacity levels were measured and the effect of e-hookah vaping on FMD was examined before and after intravenous infusion of the antioxidant ascorbic acid (n=11). Plasma nicotine and exhaled carbon monoxide levels were measured before and after the vaping session. Measurements were performed before and after sham-vaping control experiments (n=10). E-hookah vaping, which increased plasma nicotine (+4.93±0.92 ng/mL, P<0.001; mean±SE) with no changes in exhaled carbon monoxide (-0.15±0.17 ppm; P=0.479), increased mean arterial pressure (11±1 mm Hg, P<0.001) and acutely decreased FMD from 5.79±0.58% to 4.39±0.46% (P<0.001). Ascorbic acid infusion, which increased plasma total antioxidant capacity 5-fold, increased FMD at baseline (5.98±0.66% versus 9.46±0.87%, P<0.001), and prevented the acute FMD impairment by e-hookah vaping (9.46±0.87% versus 8.74±0.84%, P=0.002). All parameters were unchanged during sham studies. Conclusions E-hookah vaping has adverse effects on vascular function, likely mediated by oxidative stress, which overtime could accelerate development and progression of cardiovascular disease. Registration URL: https://ClinicalTrials.gov. Unique identifier: NCT03690427.

Keywords: ascorbic acid; electronic hookah; electronic waterpipe; endothelial function; oxidative stress.

Conflict of interest statement

Dr. Benowitz consults with pharmaceutical companies that market or are developing smoking cessation medications and has been a paid expert witness in litigation against tobacco companies. The remaining authors have no disclosures to report.

Figures

FIGURE 1. E‐hookah bowl schematic.
FIGURE 1. E‐hookah bowl schematic.
An e‐hookah bowl, placed on a traditional waterpipe, is a rechargeable battery‐operated device consisting of a power source and a heating element vaporizing flavored e‐hookah liquid. As the user inhales through the hose, the negative pressure generated causes the aerosol to pass through the water‐filled basin and into the user’s mouth.
FIGURE 2. Acute effects of e‐hookah vs…
FIGURE 2. Acute effects of e‐hookah vs sham vaping on endothelial function.
(A) Individual and mean percentage changes before and after 30‐minute of e‐hookah vaping. (B) Individual and mean percentage changes before and after 30‐minute of sham vaping. Statistical analysis is by Student t‐test. FMD indicates flow‐mediated dilation.
FIGURE 3. Effects of intravenous ascorbic acid…
FIGURE 3. Effects of intravenous ascorbic acid on baseline endothelial function.
Group mean and individual responses depicting baseline augmentation in endothelial function pre‐e‐hookah vaping without vs with intravenous infusion of ascorbic acid. White circles, individual responses. Statistical analysis is by Student t‐test. FMD indicates flow‐mediated dilation.
FIGURE 4. Acute effects of e‐hookah vaping…
FIGURE 4. Acute effects of e‐hookah vaping without and with pretreatment of intravenous ascorbic acid on endothelial function.
(A) Group mean depicting acute reductions in endothelial function in responses to 30‐minute e‐hookah vaping without vs with intravenous infusion of ascorbic acid. (B) Group mean and individual responses depicting acute reductions in endothelial function in responses to 30‐minute e‐hookah vaping without vs with intravenous infusion of ascorbic acid. White circles, individual responses; filled circles, group mean. Statistical analysis is by Student t‐test. FMD indicates flow‐mediated dilation.

References

    1. Bhatnagar A, Whitsel LP, Ribisl KM, Bullen C, Chaloupka F, Piano MR, Robertson RM, McAuley T, Goff D, Benowitz N. Electronic cigarettes: a policy statement from the American Heart Association. Circulation. 2014;130:1418–1436. DOI: 10.1161/CIR.0000000000000107.
    1. Gentzke AS, Creamer M, Cullen KA, Ambrose BK, Willis G, Jamal A, King BA. Vital signs: tobacco product use among middle and high school students ‐ United States, 2011–2018. MMWR Morb Mortal Wkly Rep. 2019;68:157–164.
    1. Rezk‐Hanna M, Toyama J, Ikharo E, Brecht ML, Benowitz NL. E‐Hookah versus E‐Cigarettes: findings from wave 2 of the PATH study (2014–2015). Am J Prev Med. 2019;57:e163–e173. DOI: 10.1016/j.amepre.2019.05.007.
    1. Pope CA 3rd, Burnett RT, Krewski D, Jerrett M, Shi Y, Calle EE, Thun MJ. Cardiovascular mortality and exposure to airborne fine particulate matter and cigarette smoke: shape of the exposure‐response relationship. Circulation. 2009;120:941–948. DOI: 10.1161/CIRCULATIONAHA.109.857888.
    1. Bhatnagar A, Maziak W, Eissenberg T, Ward KD, Thurston G, King BA, Sutfin EL, Cobb CO, Griffiths M, Goldstein LB, et al. Water pipe (hookah) smoking and cardiovascular disease risk: a scientific statement from the American Heart Association. Circulation. 2019;139:e917–e936. DOI: 10.1161/CIR.0000000000000671.
    1. Shafagoj YA, Mohammed FI. Levels of maximum end‐expiratory carbon monoxide and certain cardiovascular parameters following hubble‐bubble smoking. Saudi Med J. 2002;23:953–958.
    1. British‐American Tobacco Co, Ltd , Horsewell H. Effect of water on the selective filtrational properties of cigarette filters. British American Tobacco; 1967.
    1. Rezk‐Hanna M, Mosenifar Z, Benowitz NL, Rader F, Rashid M, Davoren K, Moy NB, Doering L, Robbins W, Sarna L, et al. High carbon monoxide levels from charcoal combustion mask acute endothelial dysfunction induced by hookah (Waterpipe) smoking in young adults. Circulation. 2019;139:2215–2224. DOI: 10.1161/CIRCULATIONAHA.118.037375.
    1. Rochette L, Cottin Y, Zeller M, Vergely C. Carbon monoxide: mechanisms of action and potential clinical implications. Pharmacol Ther. 2013;137:133–152. DOI: 10.1016/j.pharmthera.2012.09.007.
    1. Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, et al. Expert consensus and evidence‐based recommendations for the assessment of flow‐mediated dilation in humans. Eur Heart J. 2019. DOI: 10.1093/eurheartj/ehz350.
    1. Black MA, Cable NT, Thijssen DH, Green DJ. Importance of measuring the time course of flow‐mediated dilatation in humans. Hypertension. 2008;51:203–210. DOI: 10.1161/HYPERTENSIONAHA.107.101014.
    1. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow‐mediated dilation. Hypertension. 2010;55:1075–1085. DOI: 10.1161/HYPERTENSIONAHA.110.150821.
    1. Pyke KE, Dwyer EM, Tschakovsky ME. Impact of controlling shear rate on flow‐mediated dilation responses in the brachial artery of humans. J Appl Physiol. 1985;2004(97):499–508. DOI: 10.1152/japplphysiol.01245.2003.
    1. Williams MR, Westerman RA, Kingwell BA, Paige J, Blombery PA, Sudhir K, Komesaroff PA. Variations in endothelial function and arterial compliance during the menstrual cycle. J Clin Endocrinol Metab. 2001;86:5389–5395. DOI: 10.1210/jcem.86.11.8013.
    1. Miller NJ, Rice‐Evans C, Davies MJ, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci (Lond). 1993;84:407–412. DOI: 10.1042/cs0840407.
    1. Jacob P 3rd, Yu L, Wilson M, Benowitz NL. Selected ion monitoring method for determination of nicotine, cotinine and deuterium‐labeled analogs: absence of an isotope effect in the clearance of (S)‐nicotine‐3',3'‐d2 in humans. Biol Mass Spectrom. 1991;20:247–252. DOI: 10.1002/bms.1200200503.
    1. Shihadeh A, Azar S, Antonios C, Haddad A. Towards a topographical model of narghile water‐pipe cafe smoking: a pilot study in a high socioeconomic status neighborhood of Beirut, Lebanon. Pharmacol Biochem Behav. 2004;79:75–82. DOI: 10.1016/j.pbb.2004.06.005.
    1. Maziak W, Rastam S, Ibrahim I, Ward KD, Shihadeh A, Eissenberg T. CO exposure, puff topography, and subjective effects in waterpipe tobacco smokers. Nicotine Tob Res. 2009;11:806–811. DOI: 10.1093/ntr/ntp066.
    1. Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow‐mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004;556:315–324. DOI: 10.1113/jphysiol.2003.057042.
    1. Jackson TS, Xu A, Vita JA, Keaney JF Jr. Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ Res. 1998;83:916–922. DOI: 10.1161/01.RES.83.9.916.
    1. Bendich A, Machlin L, Scandurra O, Burton GW, Wayner DDM. The antioxidant role of vitamin C. Adv Free Radic Biol Med. 1986;2:419–444. DOI: 10.1016/S8755-9668(86)80021-7.
    1. Sherman DL, Keaney JF Jr, Biegelsen ES, Duffy SJ, Coffman JD, Vita JA. Pharmacological concentrations of ascorbic acid are required for the beneficial effect on endothelial vasomotor function in hypertension. Hypertension. 2000;35:936–941. DOI: 10.1161/01.HYP.35.4.936.
    1. Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, Giusti C, Salvetti A. Physical activity prevents age‐related impairment in nitric oxide availability in elderly athletes. Circulation. 2000;101:2896–2901. DOI: 10.1161/01.CIR.101.25.2896.
    1. Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A. Age‐related reduction of NO availability and oxidative stress in humans. Hypertension. 2001;38:274–279. DOI: 10.1161/01.HYP.38.2.274.
    1. May JM. How does ascorbic acid prevent endothelial dysfunction? Free Radic Biol Med. 2000;28:1421–1429. DOI: 10.1016/S0891-5849(00)00269-0.
    1. Carnevale R, Sciarretta S, Violi F, Nocella C, Loffredo L, Perri L, Peruzzi M, Marullo AGM, De Falco E, Chimenti I, et al. Acute impact of tobacco vs electronic cigarette smoking on oxidative stress and vascular function. Chest. 2016;150:606–612. DOI: 10.1016/j.chest.2016.04.012.
    1. Chaumont M, de Becker B, Zaher W, Culié A, Deprez G, Mélot C, Reyé F, Van Antwerpen P, Delporte C, Debbas N, et al. Differential effects of E‐cigarette on microvascular endothelial function, arterial stiffness and oxidative stress: a randomized crossover trial. Sci Rep. 2018;8:10378. DOI: 10.1038/s41598-018-28723-0.
    1. Kuntic M, Oelze M, Steven S, Kröller‐Schön S, Stamm P, Kalinovic S, Frenis K, Vujacic‐Mirski K, Bayo Jimenez MT, Kvandova M, et al. Short‐term e‐cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX‐2). Eur Heart J. 2020;41:2472–2483. DOI: 10.1093/eurheartj/ehz772.
    1. George J, Hussain M, Vadiveloo T, Ireland S, Hopkinson P, Struthers AD, Donnan PT, Khan F, Lang CC. Cardiovascular effects of switching from tobacco cigarettes to electronic cigarettes. J Am Coll Cardiol. 2019;74:3112–3120. DOI: 10.1016/j.jacc.2019.09.067.
    1. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol. 2004;43:1731–1737. DOI: 10.1016/j.jacc.2003.12.047.
    1. Benowitz NL. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis. 2003;46:91–111. DOI: 10.1016/S0033-0620(03)00087-2.
    1. Heitzer T, Just H, Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation. 1996;94:6–9. DOI: 10.1161/01.CIR.94.1.6.
    1. Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension. 2005;45:1107–1112. DOI: 10.1161/01.HYP.0000165678.63373.8c.
    1. Trinity JD, Wray DW, Witman MA, Layec G, Barrett‐O'Keefe Z, Ives SJ, Conklin JD, Reese V, Zhao J, Richardson RS. Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide‐mediated mechanism. Am J Physiol Heart Circ Physiol. 2016;310:H765–H774. DOI: 10.1152/ajpheart.00817.2015.
    1. Baker TA, Milstien S, Katusic ZS. Effect of vitamin C on the availability of tetrahydrobiopterin in human endothelial cells. J Cardiovasc Pharmacol. 2001;37:333–338. DOI: 10.1097/00005344-200103000-00012.
    1. Huang A, Vita JA, Venema RC, Keaney JF Jr. Ascorbic acid enhances endothelial nitric‐oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem. 2000;275:17399–17406. DOI: 10.1074/jbc.M002248200.
    1. Wever RM, van Dam T, van Rijn HJ, de Groot F, Rabelink TJ. Tetrahydrobiopterin regulates superoxide and nitric oxide generation by recombinant endothelial nitric oxide synthase. Biochem Biophys Res Commun. 1997;237:340–344. DOI: 10.1006/bbrc.1997.7069.
    1. Ting HH, Timimi FK, Haley EA, Roddy MA, Ganz P, Creager MA. Vitamin C improves endothelium‐dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation. 1997;95:2617–2622. DOI: 10.1161/01.CIR.95.12.2617.
    1. Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A. Vitamin C improves endothelium‐dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. 1998;97:2222–2229. DOI: 10.1161/01.CIR.97.22.2222.
    1. Timimi FK, Ting HH, Haley EA, Roddy MA, Ganz P, Creager MA. Vitamin C improves endothelium‐dependent vasodilation in patients with insulin‐dependent diabetes mellitus. J Am Coll Cardiol. 1998;31:552–557. DOI: 10.1016/S0735-1097(97)00536-6.
    1. Goel R, Durand E, Trushin N, Prokopczyk B, Foulds J, Elias RJ, Richie JP Jr. Highly reactive free radicals in electronic cigarette aerosols. Chem Res Toxicol. 2015;28:1675–1677. DOI: 10.1021/acs.chemrestox.5b00220.
    1. Anderson C, Majeste A, Hanus J, Wang S. E‐cigarette aerosol exposure induces reactive oxygen species, DNA damage, and cell death in vascular endothelial cells. Toxicol Sci. 2016;154:332–340. DOI: 10.1093/toxsci/kfw166.
    1. Bitzer ZT, Goel R, Reilly SM, Foulds J, Muscat J, Elias RJ, Richie JP Jr. Effects of solvent and temperature on free radical formation in electronic cigarette aerosols. Chem Res Toxicol. 2018;31:4–12. DOI: 10.1021/acs.chemrestox.7b00116.
    1. Son Y, Mishin V, Laskin JD, Mainelis G, Wackowski OA, Delnevo C, Schwander S, Khlystov A, Samburova V, Meng Q. Hydroxyl radicals in E‐cigarette vapor and E‐vapor oxidative potentials under different vaping patterns. Chem Res Toxicol. 2019;32:1087–1095. DOI: 10.1021/acs.chemrestox.8b00400.
    1. Dawkins L, Cox S, Goniewicz M, McRobbie H, Kimber C, Doig M, Kosmider L. 'Real‐world' compensatory behaviour with low nicotine concentration e‐liquid: subjective effects and nicotine, acrolein and formaldehyde exposure. Addiction. 2018;113:1874–1882. DOI: 10.1111/add.14271.
    1. Smets J, Baeyens F, Chaumont M, Adriaens K, Van Gucht D. When less is more: vaping low‐nicotine vs. high‐nicotine E‐liquid is compensated by increased wattage and higher liquid consumption. Int J Environ Res Public Health. 2019;16. DOI: 10.3390/ijerph16050723.
    1. Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: implications for electronic cigarette use. Trends Cardiovasc Med. 2016;26:515–523. DOI: 10.1016/j.tcm.2016.03.001.
    1. Bull HA, Pittilo RM, Woolf N, Machin SJ. The effect of nicotine on human endothelial cell release of prostaglandins and ultrastructure. Br J Exp Pathol. 1988;69:413–421.
    1. Tonnessen BH, Severson SR, Hurt RD, Miller VM. Modulation of nitric‐oxide synthase by nicotine. J Pharmacol Exp Ther. 2000;295:601–606.
    1. Fetterman JL, Weisbrod RM, Feng B, Bastin R, Tuttle ST, Holbrook M, Baker G, Robertson RM, Conklin DJ, Bhatnagar A, et al. Flavorings in tobacco products induce endothelial cell dysfunction. Arterioscler Thromb Vasc Biol. 2018;38:1607–1615. DOI: 10.1161/ATVBAHA.118.311156.
    1. Ballak DB, Brunt VE, Sapinsley ZJ, Ziemba BP, Richey JJ, Zigler MC, Johnson LC, Gioscia‐Ryan RA, Culp‐Hill R, Eisenmesser EZ, et al. Short‐term interleukin‐37 treatment improves vascular endothelial function, endurance exercise capacity, and whole‐body glucose metabolism in old mice. Aging Cell. 2020;19:e13074. DOI: 10.1111/acel.13074.
    1. Shechter M, Issachar A, Marai I, Koren‐Morag N, Freinark D, Shahar Y, Shechter A, Feinberg M. Long‐term association of brachial artery flow‐mediated vasodilation and cardiovascular events in middle‐aged subjects with no apparent heart disease. Int J Cardiol. 2009;134:52–58. DOI: 10.1016/j.ijcard.2008.01.021.
    1. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow‐mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007;115:2390–2397. DOI: 10.1161/CIRCULATIONAHA.106.678276.
    1. Cornacchione J, Wagoner KG, Wiseman KD, Kelley D, Noar SM, Smith MH, Sutfin EL. Adolescent and young adult perceptions of hookah and little cigars/cigarillos: implications for risk messages. J Health Commun. 2016;21:818–825. DOI: 10.1080/10810730.2016.1177141.
    1. Griffiths M, Harmon T, Gilly M. Hubble bubble trouble: the need for education about and regulation of hookah smoking. Journal of Public Policy and Marketing. 2011;30:119–132. DOI: 10.1509/jppm.30.1.119.

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