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Among the mechanisms by which nicotine, and its major metabolite, cotinine, contribute to heart disease is the renin\u2010angiotensin\u2010aldosterone system (RAAS) activation. This increases aldosterone production from the adrenals and circulating aldosterone levels. Aldosterone is a mineralocorticoid hormone with various direct harmful effects on the myocardium, including increased reactive oxygen species (ROS) generation, which contributes significantly to cardiac mitochondrial dysfunction and cardiac aging. Aldosterone is produced in the adrenocortical zona glomerulosa (AZG) cells in response to angiotensin II (AngII), activating its type 1 receptor (AT<jats:sub>1<\/jats:sub>R). The AT<jats:sub>1<\/jats:sub>R is a G protein\u2010coupled receptor (GPCR) that leads to aldosterone biosynthesis and secretion, via signaling from both G<jats:sub>q\/11<\/jats:sub>proteins and the GPCR adapter protein \u03b2arrestin1, in AZG cells. Adrenal \u03b2arrestin1 is essential for AngII\u2013dependent adrenal aldosterone production, which aggravates heart disease. Since adrenal \u03b2arrestin1 is essential for raising circulating aldosterone in the body and tobacco compounds are also known to elevate aldosterone levels in smokers, accelerating heart disease progression, our central hypothesis is that nicotine and cotinine increase aldosterone levels to induce cardiac injury by stimulating adrenal \u03b2arrestin1. In the present review, we provide an overview of the current literature of the physiology and pharmacology of adrenal aldosterone production regulation, of the effects of tobacco on this process and, finally, of the effects of tobacco and aldosterone on cardiac structure and function, with a particular focus on cardiac mitochondrial function. We conclude our literature account with a brief experimental outline, as well as with some therapeutic perspectives of our pharmacological hypothesis, that is that adrenal \u03b2arrestin1 is a novel molecular target for preventing tobacco\u2013induced hyperaldosteronism, thereby also ameliorating tobacco\u2013related heart disease development.<\/jats:p>","DOI":"10.1002\/prp2.497","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T09:33:54Z","timestamp":1560936834000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Adrenal \u03b2arrestin1 targeting for tobacco\u2013associated cardiac dysfunction treatment: Aldosterone production as the mechanistic link"],"prefix":"10.1002","volume":"7","author":[{"given":"Maria E","family":"Solesio","sequence":"first","affiliation":[{"name":"Department of Basic Sciences New York University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erna","family":"Mitaishvili","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences New York University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9817-6319","authenticated-orcid":false,"given":"Anastasios","family":"Lymperopoulos","sequence":"additional","affiliation":[{"name":"Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences Nova Southeastern University College of Pharmacy Fort Lauderdale, Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,6,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06017"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20070123"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra000050"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01307.2005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.5.1730"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030207"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2003.12.020"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04488"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v9.i3.200"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19123764"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/oso\/9780192616142.003.0004","volume-title":"Nicotine Psychopharmacology","author":"Benowitz NL","year":"1990"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.175"},{"issue":"2","key":"e_1_2_9_15_1","first-page":"81","article-title":"The influence of chronic subcutaneous nicotine administration on aldosterone and corticosterone plasma concentrations and the plasma renin activity","volume":"62","author":"Seifert J","year":"1984","journal-title":"Klin Wochenschr"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.5.8156919"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.03.015"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1470320315576256"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00099.2018"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.07.037"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000669"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6745a5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntu213"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2019.04.006"},{"key":"e_1_2_9_25_1","first-page":"415","article-title":"International union of pharmacology. 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