Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Am J Physiol Heart Circ Physiol. 2022 Nov 1;323(5):H941-H948. doi: 10.1152/ajpheart.00467.2022. Epub 2022 Oct 7.
Electronic cigarette use has increased globally prompting calls for improved understanding of nicotine's cardiovascular health effects. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension and right ventricular (RV) remodeling in male mice, but not female mice, suggesting sex differences in nicotine-related pathology. Clinically, biological females develop pulmonary hypertension more often but have less severe disease than biological males, likely because of the cardiopulmonary protective effects of estrogen. Nicotine is also metabolized more rapidly in biological females because of differences in cytochrome-450 activity, which are thought to be mediated by female sex hormones. These findings led us to hypothesize that female mice are protected against nicotine-induced pulmonary hypertension by an ovarian hormone-dependent mechanism. In this study, intact and ovariectomized (OVX) female mice were exposed to chronic, inhaled nicotine or room air for 12 h/day for 10-12 wk. We report no differences in serum cotinine levels between intact and OVX mice. In addition, we found no structural (RV or left ventricular dimensions and Fulton index) or functional (RV systolic pressure, pulmonary vascular resistance, cardiac output, ejection fraction, and fractional shortening) evidence of cardiopulmonary dysfunction in intact or OVX mice. We conclude that ovarian hormones do not mediate cardiopulmonary protection against nicotine-induced pulmonary hypertension. Due to profound sex differences in clinical pulmonary hypertension pathogenesis and nicotine metabolism, further studies are necessary to elucidate mechanisms underlying protection from nicotine-induced pathology in female mice. The emergence of electronic cigarettes poses a threat to cardiovascular and pulmonary health, but the direct contribution of nicotine to these disease processes is largely unknown. Our laboratory has previously shown that chronic, inhaled nicotine induces pulmonary hypertension and right ventricular remodeling in male mice, but not female mice. This study using a bilateral ovariectomy model suggests that the cardiopulmonary protection observed in nicotine-exposed female mice may be independent of ovarian hormones.
电子烟在全球范围内的使用有所增加，这促使人们呼吁更好地了解尼古丁对心血管健康的影响。我们的研究小组之前已经证明，慢性吸入尼古丁会导致雄性小鼠发生肺动脉高压和右心室（RV）重构，但不会导致雌性小鼠发生这种情况，这表明尼古丁相关病理学存在性别差异。临床上，生物女性比生物男性更常发生肺动脉高压，但疾病程度较轻，这可能是由于雌激素对心肺的保护作用。由于细胞色素 P450 活性的差异，尼古丁在生物女性体内的代谢速度也更快，而这种差异被认为是由女性性激素介导的。这些发现使我们假设，卵巢激素依赖性机制可能使雌性小鼠免受尼古丁引起的肺动脉高压的影响。在这项研究中，完整和卵巢切除（OVX）的雌性小鼠每天暴露于慢性吸入尼古丁或室内空气 12 小时，持续 10-12 周。我们报告称，完整和 OVX 小鼠的血清可替宁水平没有差异。此外，我们在完整或 OVX 小鼠中没有发现心肺功能障碍的结构（RV 或左心室尺寸和富尔顿指数）或功能（RV 收缩压、肺血管阻力、心输出量、射血分数和分数缩短）证据。我们的结论是，卵巢激素不能介导对尼古丁引起的肺动脉高压的心肺保护。由于临床肺动脉高压发病机制和尼古丁代谢存在显著的性别差异，因此需要进一步研究来阐明雌性小鼠免受尼古丁引起的病理学的保护机制。电子烟的出现对心血管和肺部健康构成了威胁，但尼古丁对这些疾病过程的直接贡献在很大程度上尚不清楚。我们的实验室之前已经表明，慢性吸入尼古丁会导致雄性小鼠发生肺动脉高压和右心室重构，但不会导致雌性小鼠发生这种情况。这项使用双侧卵巢切除术模型的研究表明，在暴露于尼古丁的雌性小鼠中观察到的心肺保护可能与卵巢激素无关。
