(Circulation. 1995;91:1154-1160.)
© 1995 American Heart Association, Inc.
Articles |
Testosterone Relaxes Rabbit Coronary Arteries and Aorta
From the Department of Cardiac Medicine, National Heart and Lung Institute, London, and the Cardiovascular Research Institute (K.C.), University of California, San Francisco.
Correspondence to Dr Peter Collins, Department of Cardiac Medicine, National Heart and Lung Institute, London SW3 6LY, UK.
Background Until menopause, women appear to be protected from coronary heart disease. Evidence suggests that estrogen may play a role in the protection of the cardiovascular system by exerting a beneficial effect on risk factors such as cholesterol metabolism and by a direct effect on the coronary arteries. To date there has been no evidence linking testosterone with the occurrence of coronary heart disease. Testosterone may affect the cardiovascular system directly, thus partially explaining the difference in the incidence of coronary artery disease in men and premenopausal women. The purpose of this study was to assess the direct effect of testosterone and a number of testosterone analogues on rabbit coronary arteries and aorta in vitro.
Methods and Results Rings of coronary artery and aorta of
adult male or nonpregnant female New Zealand White rabbits were
suspended in organ baths containing Krebs solution; isometric tension
then was measured. The response to testosterone was investigated in
prostaglandin F2
(PGF2)- and
KCl-contracted rings. The effects of endothelium and nitric oxide
synthase, prostaglandin synthetase, and guanylate cyclase inhibition on
testosterone-induced relaxation were investigated. The effects of
ATP-sensitive potassium channels and potassium conductance were also
assessed. Relaxing responses in the presence of aromatase inhibition
and testosterone receptor blockade were performed. The relaxing
responses to the testosterone analogues etiocholan-3ß-ol-17-one,
epiandrosterone, 17ß-hydroxy-5-androst-1-en-3-one,
androst-16-en-3-ol, and testosterone enanthanate were measured.
Testosterone relaxed rabbit coronary arteries and aorta. There was no
significant difference between the relaxation effect of testosterone
with or without endothelium. Similar results were obtained from male
and nonpregnant female rabbits. The relaxing response of testosterone
in the coronary artery was significantly greater than in the aorta. The
relaxing response of testosterone in the coronary artery was
significantly reduced by the potassium channel inhibitor barium
chloride but not by the ATP-sensitive potassium channel inhibitor
glibenclamide. The relaxing response to testosterone was greater in
PGF2-contracted rings compared with KCl-contracted
rings. Inhibitors of nitric oxide synthase, prostaglandin synthetase,
and guanylate cyclase did not affect relaxation induced by
testosterone. Inhibition of aromatase and testosterone receptors did
not affect relaxation. Testosterone did not shift the rabbit coronary
arterial calcium concentration–dependent contraction curves, whereas
verapamil did. There were, however, significant differences in the
relaxing response to testosterone compared with testosterone analogues.
Testosterone was the most potent relaxing agent, suggesting that there
may be a structure-function relation in the relaxing response.
Conclusions Testosterone induces endothelium-independent relaxation in isolated rabbit coronary artery and aorta, which is neither mediated by prostaglandin I2 or cyclic GMP. Potassium conductance and potassium channels but not ATP-sensitive potassium channels may be involved partially in the mechanism of testosterone-induced relaxation. The in vitro relaxation is independent of sex and of a classic receptor. The coronary artery is significantly more sensitive to relaxation by testosterone than the aorta. Testosterone is a more potent relaxing agent of rabbit coronary artery than other testosterone analogues.
Key Words: hormones • arteries • endothelium • aorta
This article has been cited by other articles:
 |
|
 |
|
  L. M. Montano, E. Calixto, A. Figueroa, E. Flores-Soto, V. Carbajal, and M. Perusquia Relaxation of Androgens on Rat Thoracic Aorta: Testosterone Concentration Dependent Agonist/Antagonist L-Type Ca2+ Channel Activity, and 5{beta}-Dihydrotestosterone Restricted to L-Type Ca2+ Channel Blockade Endocrinology, May 1, 2008; 149(5): 2517 - 2526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Hydock, C.-Y. Lien, C. M. Schneider, and R. Hayward Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3254 - H3264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lahm, K. M. Patel, P. R. Crisostomo, T. A. Markel, M. Wang, C. Herring, and D. R. Meldrum Endogenous estrogen attenuates pulmonary artery vasoreactivity and acute hypoxic pulmonary vasoconstriction: the effects of sex and menstrual cycle Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E865 - E871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Gonzalez-Montelongo, R. Marin, T. Gomez, and M. Diaz Androgens Differentially Potentiate Mouse Intestinal Smooth Muscle by Nongenomic Activation of Polyamine Synthesis and Rho Kinase Activation Endocrinology, December 1, 2006; 147(12): 5715 - 5729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Castillo, G. Ceballos, D. Rodriguez, C. Villanueva, R. Medina, J. Lopez, E. Mendez, and E. F. Castillo Effects of estradiol on phenylephrine contractility associated with intracellular calcium release in rat aorta Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1388 - C1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hall, R. D. Jones, T. H. Jones, K. S. Channer, and C. Peers Selective Inhibition of L-Type Ca2+ Channels in A7r5 Cells by Physiological Levels of Testosterone Endocrinology, June 1, 2006; 147(6): 2675 - 2680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Norata, G. Tibolla, P. M. Seccomandi, A. Poletti, and A. L. Catapano Dihydrotestosterone Decreases Tumor Necrosis Factor-{alpha} and Lipopolysaccharide-Induced Inflammatory Response in Human Endothelial Cells J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Cunha, M. Jose, C. S. Moura, C. F. Bernardes, A. P. Tanno, and F. K. Marcondes Vascular Sensitivity to Phenylephrine in Rats Submitted to Anaerobic Training and Nandrolone Treatment Hypertension, October 1, 2005; 46(4): 1010 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wang, B. M. Tsai, A. Kher, L. B. Baker, G. M. Wairiuko, and D. R. Meldrum Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H221 - H226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.M. Rivera-Woll, M. Papalia, S.R. Davis, and H.G. Burger Androgen insufficiency in women: diagnostic and therapeutic implications Hum. Reprod. Update, September 1, 2004; 10(5): 421 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C J Malkin, P J Pugh, P D Morris, K E Kerry, R D Jones, T H Jones, and K S Channer Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life Heart, August 1, 2004; 90(8): 871 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sierra-Ramirez, T. Morato, R. Campos, I. Rubio, C. Calzada, E. Mendez, and G. Ceballos Acute effects of testosterone on intracellular Ca2+ kinetics in rat coronary endothelial cells are exerted via aromatization to estrogens Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H63 - H71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Littleton-Kearney and P. D. Hurn Testosterone as a Modulator of Vascular Behavior Biol Res Nurs, April 1, 2004; 5(4): 276 - 285. [Abstract] [PDF]
|
|
|
|
 |
|
 J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Gonzales, D. N. Krause, and S. P. Duckles Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H552 - H560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mendelsohn and G. M.C. Rosano Hormonal Regulation of Normal Vascular Tone in Males Circ. Res., December 12, 2003; 93(12): 1142 - 1145. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Gupte, M. Arshad, S. Viola, P. M. Kaminski, Z. Ungvari, G. Rabbani, A. Koller, and M. S. Wolin Pentose phosphate pathway coordinates multiple redox-controlled relaxing mechanisms in bovine coronary arteries Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2316 - H2326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Muller, Y. T. van der Schouw, J. H. H. Thijssen, and D. E. Grobbee Endogenous Sex Hormones and Cardiovascular Disease in Men J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5076 - 5086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Callies, H. Stromer, R. H. G. Schwinger, B. Bolck, K. Hu, S. Frantz, A. Leupold, S. Beer, B. Allolio, and A. W. Bonz Administration of Testosterone Is Associated with a Reduced Susceptibility to Myocardial Ischemia Endocrinology, October 1, 2003; 144(10): 4478 - 4483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chatrath, K. L. Ronningen, S. R. Severson, P. LaBreche, M. Jayachandran, M. P. Bracamonte, and V. M. Miller Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1168 - H1176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Azad, S. Pitale, W. E. Barnes, and N. Friedman Testosterone Treatment Enhances Regional Brain Perfusion in Hypogonadal Men J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3064 - 3068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fukui, Y. Kitagawa, N. Nakamura, M. Kadono, S. Mogami, C. Hirata, N. Ichio, K. Wada, G. Hasegawa, and T. Yoshikawa Association Between Serum Testosterone Concentration and Carotid Atherosclerosis in Men With Type 2 Diabetes Diabetes Care, June 1, 2003; 26(6): 1869 - 1873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhasin and K. Herbst Testosterone and Atherosclerosis Progression in Men Diabetes Care, June 1, 2003; 26(6): 1929 - 1931. [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Pugh, T. H. Jones, and K. S. Channer Acute haemodynamic effects of testosterone in men with chronic heart failure Eur. Heart J., May 2, 2003; 24(10): 909 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. W. Wu and A. von Eckardstein Androgens and Coronary Artery Disease Endocr. Rev., April 1, 2003; 24(2): 183 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann, M. Brune, and E. Nieschlag Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5030 - 5037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Baltatu, C. Cayla, R. Iliescu, D. Andreev, C. Jordan, and M. Bader Abolition of Hypertension-Induced End-Organ Damage by Androgen Receptor Blockade in Transgenic Rats Harboring the Mouse Ren-2 Gene J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2681 - 2687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Kenny, K. M. Prestwood, C. A. Gruman, G. Fabregas, B. Biskup, and G. Mansoor Effects of Transdermal Testosterone on Lipids and Vascular Reactivity in Older Men With Low Bioavailable Testosterone Levels J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2002; 57(7): M460 - 465. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. A. Gupte, K.-X. Li, T. Okada, K. Sato, and M. Oka Inhibitors of Pentose Phosphate Pathway Cause Vasodilation: Involvement of Voltage-Gated Potassium Channels J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 299 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ling, A. Dai, M. R. I. Williams, K. Myles, R. J. Dilley, P. A. Komesaroff, and K. Sudhir Testosterone (T) Enhances Apoptosis-Related Damage in Human Vascular Endothelial Cells Endocrinology, March 1, 2002; 143(3): 1119 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sader and D. S. Celermajer Endothelial function, vascular reactivity and gender differences in the cardiovascular system Cardiovasc Res, February 15, 2002; 53(3): 597 - 604. [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Heaps and D. K. Bowles Gender-specific K+-channel contribution to adenosine-induced relaxation in coronary arterioles J Appl Physiol, February 1, 2002; 92(2): 550 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Yang, E. Perez, J. Cutright, R. Liu, Z. He, A. L. Day, and J. W. Simpkins Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model J Appl Physiol, January 1, 2002; 92(1): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Q. Ding and J. N. Stallone Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation J Appl Physiol, December 1, 2001; 91(6): 2742 - 2750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann, M. Brune, B. Kornmann, J. Gromoll, S. von Eckardstein, A. von Eckardstein, and E. Nieschlag The CAG Repeat Polymorphism in the AR Gene Affects High Density Lipoprotein Cholesterol and Arterial Vasoreactivity J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4867 - 4873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Deenadayalu, R. E. White, J. N. Stallone, X. Gao, and A. J. Garcia Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1720 - H1727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Smith, S. Bennett, L. M. Evans, H. G. Kynaston, M. Parmar, M. D. Mason, J. R. Cockcroft, M. F. Scanlon, and J. S. Davies The Effects of Induced Hypogonadism on Arterial Stiffness, Body Composition, and Metabolic Parameters in Males with Prostate Cancer J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4261 - 4267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Manolagas and S. Kousteni Perspective: Nonreproductive Sites of Action of Reproductive Hormones Endocrinology, June 1, 2001; 142(6): 2200 - 2204. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hanke, C. Lenz, B. Hess, K.-D. Spindler, and W. Weidemann Effect of Testosterone on Plaque Development and Androgen Receptor Expression in the Arterial Vessel Wall Circulation, March 13, 2001; 103(10): 1382 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sader, K. A. Griffiths, R. J. McCredie, D. J. Handelsman, and D. S. Celermajer Androgenic anabolic steroids and arterial structure and function in male bodybuilders J. Am. Coll. Cardiol., January 1, 2001; 37(1): 224 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Worboys, D. Kotsopoulos, H. Teede, B. McGrath, and S. R. Davis Evidence That Parenteral Testosterone Therapy May Improve Endothelium-Dependent and -Independent Vasodilation in Postmenopausal Women Already Receiving Estrogen J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 158 - 161. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Falkenstein, H.-C. Tillmann, M. Christ, M. Feuring, and M. Wehling Multiple Actions of Steroid Hormones---A Focus on Rapid, Nongenomic Effects Pharmacol. Rev., December 1, 2000; 52(4): 513 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. English, R. P. Steeds, T. H. Jones, M. J. Diver, and K. S. Channer Low-Dose Transdermal Testosterone Therapy Improves Angina Threshold in Men With Chronic Stable Angina : A Randomized, Double-Blind, Placebo-Controlled Study Circulation, October 17, 2000; 102(16): 1906 - 1911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.J. Pugh, K.M. English, T.H. Jones, and K.S. Channer Testosterone: a natural tonic for the failing heart? QJM, October 1, 2000; 93(10): 689 - 694. [Full Text] [PDF]
|
|
|
|
|
|
G. G. Geary, D. N. Krause, and S. P. Duckles Gonadal hormones affect diameter of male rat cerebral arteries through endothelium-dependent mechanisms Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H610 - H618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.M English, O Mandour, R.P Steeds, M.J Diver, T.H Jones, and K.S Channer Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms Eur. Heart J., June 1, 2000; 21(11): 890 - 894. [Abstract] [PDF]
|
|
|
|
|
|
C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]
|
|
|
|
|
|
H. Teoh, A. Quan, and R. Y.K Man Acute impairment of relaxation by low levels of testosterone in porcine coronary arteries Cardiovasc Res, March 1, 2000; 45(4): 1010 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Honda, T. Unemoto, and H. Kogo Different Mechanisms for Testosterone-Induced Relaxation of Aorta Between Normotensive and Spontaneously Hypertensive Rats Hypertension, December 1, 1999; 34(6): 1232 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Webb, J. G. McNeill, C. S. Hayward, D. de Zeigler, and P. Collins Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart Disease Circulation, October 19, 1999; 100(16): 1690 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Murphy and R. A. Khalil Decreased [Ca2+]i during Inhibition of Coronary Smooth Muscle Contraction by 17beta -Estradiol, Progesterone, and Testosterone J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 44 - 52. [Abstract] [Full Text]
|
|
|
|
|
|
G.P. Bernini, M. Sgro’, A. Moretti, G.F. Argenio, C.O. Barlascini, R. Cristofani, and A. Salvetti Endogenous Androgens and Carotid Intimal-Medial Thickness in Women J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2008 - 2012. [Abstract] [Full Text]
|
|
|
|
|
|
P. Alexandersen, J. Haarbo, I. Byrjalsen, H. Lawaetz, and C. Christiansen Natural Androgens Inhibit Male Atherosclerosis : A Study in Castrated, Cholesterol-Fed Rabbits Circ. Res., April 16, 1999; 84(7): 813 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. C. Rosano, F. Leonardo, P. Pagnotta, F. Pelliccia, G. Panina, E. Cerquetani, P. L. della Monica, B. Bonfigli, M. Volpe, and S. L. Chierchia Acute Anti-Ischemic Effect of Testosterone in Men With Coronary Artery Disease Circulation, April 6, 1999; 99(13): 1666 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Crews and R. A. Khalil Antagonistic Effects of 17ß-Estradiol, Progesterone, and Testosterone on Ca2+ Entry Mechanisms of Coronary Vasoconstriction Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 1034 - 1040. [Abstract] [Full Text] [PDF]
|
|