Author + information
- Received May 29, 1996
- Revision received November 20, 1996
- Accepted December 4, 1996
- Published online March 15, 1997.
- Stuart J Hutchison, MD, FRCP(C), FACCA,
- Krishnankutty Sudhir, MD, PhD, FRACPA,*,
- Tony M Chou, MD, FACCA,
- Richard E Sievers, BScA,
- Bo-Qing Zhu, MD, FACCA,
- Yi-Ping Sun, MDA,
- Prakash C Deedwania, MD, FACCA,
- Stanton A Glantz, PhD, FACCA,
- William W Parmley, MD, FACCA and
- Kanu Chatterjee, MB, FRCP, FACCA
- ↵*Dr. Krishankutty Sudhir, Division of Cardiology, University of California San Francisco, Moffit Hospital, Room 1186, San Francisco, California 94143.
Objectives. To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis.
Background. Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor.
Methods. New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37°C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before precontraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining.
Results. HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03).
Conclusions. Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.
(J Am Coll Cardiol 1997;29:800–7)
☆ Dr. Hutchison was supported in part by a traveling fellowship from the R. Samuel McLaughlin Foundation, Toronto, Ontario, Canada.
This study was presented in part at the 68th Annual Scientific Sessions of the American Heart Association, Anaheim, California, November 1995 and the 45th Annual Scientific Session of the American College of Cardiology, Orlando, Florida, March 1996.
↵1 All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.
- Received May 29, 1996.
- Revision received November 20, 1996.
- Accepted December 4, 1996.
- The American College of Cardiology