Progesterone regulation of vascular thromboxane A(2) receptors in rhesus monkeys.

We hypothesized that progesterone regulates thromboxane A(2) receptor (TxA(2)R) density in primate vascular muscle and that TxA(2)R density correlates with coronary reactivity in vivo and in vitro. Reactivity to serotonin + U-46619 was determined by angiography in surgically postmenopausal [ovariectomized (Ovx)] rhesus monkeys without progesterone replacement and after 2-wk progesterone treatment (1-2 ng/ml). In untreated Ovx animals, 100 micromol/l serotonin + 1 micromol/l U-46619 (syringe concentrations) provoked vasospasm-like constrictions in six of six monkeys; zero of six progesterone-treated monkeys developed vasospasms. Sustained Ca(2+) responses in vascular muscle cells isolated from Ovx coronaries (208 +/- 63% of basal 20 min after stimulation) treated with serotonin + U-46619 contrasted with transient Ca(2+) responses (143 +/- 18% of basal and decreasing 5 min after stimulation) in progesterone-treated monkeys. The maximum density of [1S-(1I,2J(5Z),3I(1E,3R*),4I)]-7-[3-(3-hydroxy-4-(4'-[(125)I]iodophenoxy)- 1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic acid ([(125)I]-BOP) binding was greater (P < 0.01) in carotid arteries and aortic membranes from Ovx (109 +/- 11 fmol/mg) compared with progesterone-treated (43 +/- 15 fmol/mg) monkeys. TxA(2)R immunolabeling revealed greater coronary TxA(2)R labeling in Ovx compared with progesterone-treated monkeys. The results suggest that progesterone can decrease arterial TxA(2)R in Ovx monkeys.

[1]  K. Antonakis,et al.  Shifts in the affinity distribution of one class of seven-transmembrane receptors by activation of a separate class of seven-transmembrane receptors. , 2000, Biochemical pharmacology.

[2]  G. Rosano,et al.  Cardiovascular Pharmacology of Hormone Replacement Therapy , 1999, Drugs & aging.

[3]  C. L. Bethea,et al.  Ovarian steroid regulation of serotonin-1A autoreceptor messenger rna expression in the dorsal raphe of rhesus macaques , 1999, Neuroscience.

[4]  C. Bethea,et al.  Ovarian steroid effects on serotonin 1A, 2A and 2C receptor mRNA in macaque hypothalamus. , 1999, Brain research. Molecular brain research.

[5]  P. Mannon,et al.  Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2. , 1998, The Journal of clinical investigation.

[6]  R. Minshall,et al.  In vitro modulation of primate coronary vascular muscle cell reactivity by ovarian steroid hormones , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  K. Antonakis,et al.  A molecular mechanism for signaling between seven-transmembrane receptors: evidence for a redistribution of G proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  K. Schey,et al.  Expression, Characterization, and Purification of C-terminally Hexahistidine-tagged Thromboxane A2 Receptors* , 1998, The Journal of Biological Chemistry.

[9]  E. Vittinghoff,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[10]  M. Axthelm,et al.  Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. , 1998, The Journal of clinical endocrinology and metabolism.

[11]  J. Manson,et al.  Cardiovascular disease in women: a statement for healthcare professionals from the American Heart Association. Writing Group. , 1997, Circulation.

[12]  J. Abrams.  Role of endothelial dysfunction in coronary artery disease. , 1997, The American journal of cardiology.

[13]  K. Hermsmeyer,et al.  Ca2+ release mechanism of primate drug-induced coronary vasospasm. , 1997, The American journal of physiology.

[14]  J. Szumowski,et al.  Alteration of ascending thoracic aorta compliance after treatment with menotropin. , 1997, American journal of obstetrics and gynecology.

[15]  P. Libby,et al.  Cell dysfunction in atherosclerosis and the ischemic manifestations of coronary artery disease. , 1997, The American journal of cardiology.

[16]  J. Rösch,et al.  Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm , 1997, Nature Medicine.

[17]  S. Kelley,et al.  Reactivity-based coronary vasospasm independent of atherosclerosis in rhesus monkeys. , 1997, Journal of the American College of Cardiology.

[18]  C. Kessler,et al.  Estrogen replacement therapy and coagulation: Relationship to lipid and lipoprotein changes , 1997, Obstetrics and gynecology.

[19]  C. Weiner,et al.  Long-term estradiol replacement decreases contractility of guinea pig coronary arteries to the thromboxane mimetic U46619. , 1997, Circulation.

[20]  K. Egashira,et al.  Central role of vascular smooth muscle hyperreactivity in coronary hyperconstriction after balloon injury in miniature pigs , 1997, Coronary artery disease.

[21]  E. Barrett-Connor.  Sex differences in coronary heart disease. Why are women so superior? The 1995 Ancel Keys Lecture. , 1997, Circulation.

[22]  L. Ghiadoni,et al.  Menopause is associated with endothelial dysfunction in women. , 1996, Hypertension.

[23]  U. Deligonul,et al.  Provocation of coronary spasm by dobutamine stress echocardiography in a patient with angiographically minimal coronary artery disease , 1996, Clinical cardiology.

[24]  J. Manson,et al.  Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. , 1996, The New England journal of medicine.

[25]  F. Pierron,et al.  Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients. , 1996, European heart journal.

[26]  Susan R. Johnson,et al.  Effects of Estrogen or Estrogen/ Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial , 1995 .

[27]  T. Clarkson,et al.  Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys. , 1994, Journal of the American College of Cardiology.

[28]  P. Halushka,et al.  Testosterone increases thromboxane A2 receptor density and responsiveness in rat aortas and platelets. , 1994, The American journal of physiology.

[29]  W. Campbell,et al.  Decrease in vascular TxA2 receptors in a subgroup of rabbits unresponsive to a TxA2 mimetic. , 1994, The American journal of physiology.

[30]  P. Belchetz.  Hormonal treatment of postmenopausal women. , 1994, The New England journal of medicine.

[31]  K. Schrör,et al.  Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs , 1994, European journal of clinical investigation.

[32]  C. Beglinger,et al.  Circulating somatostatin‐28 is not a physiologic regulator of gastric acid production in man , 1994, European journal of clinical investigation.

[33]  E. Duzic,et al.  Androgen regulation of thromboxane A2/prostaglandin H2 receptor expression in human erythroleukemia cells. , 1993, The American journal of physiology.

[34]  M. Kupari,et al.  Left ventricular diastolic function by Doppler echocardiography in relation to hormonal replacement therapy in healthy postmenopausal women. , 1993, The American journal of cardiology.

[35]  J. Bar,et al.  The Effect of Estrogen Replacement Therapy on Platelet Aggregation and Adenosine Triphosphate Release in Postmenopausal Women , 1993, Obstetrics and gynecology.

[36]  A. Khachadurian,et al.  The inhibition of low-density lipoprotein oxidation by 17-β estradiol , 1992 .

[37]  P. Poole‐Wilson,et al.  Angina and normal coronary arteries in women: gynecologic findings. , 1992, American journal of obstetrics and gynecology.

[38]  P. Poole‐Wilson,et al.  Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1. , 1992, The American journal of physiology.

[39]  P. Halushka,et al.  Testosterone increases thromboxane A2 receptors in cultured rat aortic smooth muscle cells. , 1991, Circulation research.

[40]  E. Barrett-Connor,et al.  Estrogen and coronary heart disease in women , 1991, JAMA.

[41]  C. Christiansen,et al.  Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits. , 1991, The Journal of clinical investigation.

[42]  S. Manuck,et al.  Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone. , 1990, Arteriosclerosis.

[43]  W. Sessa,et al.  Dexamethasone selectively attenuates prostanoid-induced vasoconstrictor responses in vitro. , 1990, Circulation research.

[44]  F. Crea,et al.  Spontaneous coronary artery spasm in variant angina is caused by a local hyperreactivity to a generalized constrictor stimulus. , 1989, Journal of the American College of Cardiology.

[45]  P. Halushka,et al.  Characterization of an 125I-labeled thromboxane A2/prostaglandin H2 receptor agonist. , 1989, The Journal of pharmacology and experimental therapeutics.

[46]  F. Crea,et al.  Local coronary supersensitivity to diverse vasoconstrictive stimuli in patients with variant angina. , 1986, Circulation.

[47]  P. Ganz,et al.  New insights into the cellular mechanisms of vasospasm. , 1985, The American journal of cardiology.

[48]  P. Ganz,et al.  New insights into the cellular mechanisms of vasospas , 1985 .

[49]  A. Hendrickx,et al.  Diurnal steroid patterns during gestation in the rhesus macaque: onset, daily variation, and the effects of dexamethasone treatment. , 1981, Biology of reproduction.

[50]  I. Waldron.  Sex Differences in Coronary Heart Disease , 1978 .

[51]  D. Zipes,et al.  Effects of selective vagal and stellate ganglion stimulation of atrial refractoriness. , 1974, Cardiovascular research.

[52]  M. Gertler,et al.  Ischemic Heart Disease: Insulin, Carbohydrate, and Lipid Interrelationships , 1972, Circulation.

[53]  Y. Ito.  [Ischemic heart disease]. , 1966, Saishin igaku. Modern medicine.

[54]  W. Campbell,et al.  Vascular smooth muscle thromboxane A2 receptors mediate arachidonic acid-induced sudden death in rabbits. , 1997, Hypertension.