(Circulation. 2000;101:94.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
17ß-Estradiol Restores Endothelial Nitric Oxide Release to Shear Stress in Arterioles of Male Hypertensive Rats
From the Department of Physiology, New York Medical College, Valhalla.
Correspondence to An Huang, MD, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail an huang{at}nymc.edu
Background—Endothelial nitric oxide (NO)–mediated responses are impaired in arterioles of male spontaneously hypertensive rats (SHR), but they are still present in female SHR. We hypothesized that in vitro incubation of arterioles of male SHR with estrogen will restore NO-mediated responses by upregulation of endothelial NO synthase.
Methods and Results—Responses to increases in perfusate
flow (from 0 to 25 µL/min) and to the calcium ionophore A23187
(5x10-8 to 10-6 mol/L),
norepinephrine (NE; 10-7 to
3x10-7 mol/L), sodium nitroprusside (SNP;
10-8 to 10-6 mol/L), and adenosine
(ADO; 10-6 to 5x10-5 mol/L) were studied in
cannulated and pressurized gracilis muscle arterioles (
75 µm
in diameter) isolated from 12-week-old male SHR before and after
incubation with 10-9 mol/L 17ß-estradiol
(17ß-E2) for 16 to 18 hours. After incubation with
17ß-E2, basal diameter of arterioles was significantly
increased (by 10%), and flow-induced dilation was significantly
enhanced (79.8±2.9 versus 103.7±3.7 µm at 25 µL/min),
resulting in a lowered shear stress (62.0±9.1 versus 32.5±4.2
dyne/cm2). Also, vasoconstrictions to A23187 were reversed
to dilations (-18.7±2.2 versus 18.8±1.7 µm), and
constrictions to NE were significantly attenuated (-30.7±3.0 versus
-21.2±2.8 µm). These alterations were eliminated by ICI
182,780 (10-7 mol/L), an estrogen receptor
antagonist;
5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole
(10-5 mol/L), a transcription inhibitor; or
N
-nitro-L-arginine methyl
ester (10-4 mol/L), an inhibitor of NO
synthase, whereas they were not affected by aminoguanidine
(5x10-5 mol/L), a specific inhibitor of
inducible NO synthase. Arteriolar responses were not altered by
incubation with 17
-estradiol.
Conclusions—Estrogen, via a receptor-mediated pathway, upregulates endothelial NO synthase gene expression, leading to increased NO production, and restores the regulation of wall shear stress in arterioles of male SHR.
Key Words: endothelium • vasodilation • hormones • receptors
This article has been cited by other articles:
 |
|
 |
|
  G. Douglas, M. Natalia Cruz, L. Poston, J.-A. Gustafsson, and K. Kublickiene Functional characterization and sex differences in small mesenteric arteries of the estrogen receptor- knockout mouse Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R112 - R120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sun, C. Yan, A. Jacobson, H. Jiang, M. A. Carroll, and A. Huang Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ER{alpha} knockout mice: role of aromatase Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1239 - R1246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sun, H. Liu, C. Yan, A. Jacobson, C. Ojaimi, A. Huang, and G. Kaley COX-2 contributes to the maintenance of flow-induced dilation in arterioles of eNOS-knockout mice Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1429 - H1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gimenez, M. P. Garcia, M. Serna, B. Bonacasa, L. F. Carbonell, T. Quesada, and I. Hernandez 17{beta}-Oestradiol enhances the acute hypotensive effect of captopril in female ovariectomized spontaneously hypertensive rats Exp Physiol, July 1, 2006; 91(4): 715 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Chancey, J. D. Gardner, D. B. Murray, G. L. Brower, and J. S. Janicki Modulation of cardiac mast cell-mediated extracellular matrix degradation by estrogen Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H316 - H321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Huang, D. Sun, Z. Wu, C. Yan, M. A. Carroll, H. Jiang, J. R. Falck, and G. Kaley Estrogen Elicits Cytochrome P450--Mediated Flow-Induced Dilation of Arterioles in NO Deficiency: Role of PI3K-Akt Phosphorylation in Genomic Regulation Circ. Res., February 6, 2004; 94(2): 245 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Leung, J. J. Wang, E. Rochtchina, A. G. Tan, T. Y. Wong, R. Klein, L. D. Hubbard, and P. Mitchell Relationships between Age, Blood Pressure, and Retinal Vessel Diameters in an Older Population Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2900 - 2904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Lane Diabetic kidney disease: impact of puberty Am J Physiol Renal Physiol, October 1, 2002; 283(4): F589 - F600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Miyamoto, M. Mandai, H. Takagi, I. Suzuma, K. Suzuma, S. Koyama, A. Otani, H. Oh, and Y. Honda Contrasting Effect of Estrogen on VEGF Induction under Different Oxygen Status and Its Role in Murine ROP Invest. Ophthalmol. Vis. Sci., June 1, 2002; 43(6): 2007 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. McNeill, C. Zhang, F. Z. Stanczyk, S. P. Duckles, and D. N. Krause Estrogen Increases Endothelial Nitric Oxide Synthase via Estrogen Receptors in Rat Cerebral Blood Vessels: Effect Preserved After Concurrent Treatment With Medroxyprogesterone Acetate or Progesterone Stroke, June 1, 2002; 33(6): 1685 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Joyce, T. M. Phernetton, C. E. Shaw, M. L. Modrick, and R. R. Magness Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H342 - H348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Huang, Y. Wu, D. Sun, A. Koller, and G. Kaley Effect of estrogen on flow-induced dilation in NO deficiency: role of prostaglandins and EDHF J Appl Physiol, December 1, 2001; 91(6): 2561 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Jhund, N. Dawson, A. P. Davie, N. Sattar, J. Norrie, K. P. J. O'Kane, and J. J. V. McMurray Attenuation of endothelin-1 induced vasoconstriction by 17{beta} estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1367 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Hamilton, M. J. Brosnan, M. McIntyre, D. Graham, and A. F. Dominiczak Superoxide Excess in Hypertension and Aging : A Common Cause of Endothelial Dysfunction Hypertension, February 1, 2001; 37(2): 529 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Santizo, S. Anderson, S. Ye, H. M. Koenig, D. A. Pelligrino, and H. A. Kontos Effects of Estrogen on Leukocyte Adhesion After Transient Forebrain Ischemia Editorial Comment Stroke, September 1, 2000; 31(9): 2231 - 2235. [Abstract] [Full Text] [PDF]
|
|