© 1998 American Heart Association, Inc.
Original Contributions |
Acute Endothelin-Receptor Inhibition Does Not Attenuate Acetylcholine-Induced Coronary Vasoconstriction in Experimental Hypercholesterolemia
From the Division of Internal Medicine and Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minn.
Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu
Abstract—Endothelin (ET) may mediate
the enhanced coronary vasoconstriction associated with
hypercholesterolemia. We hypothesized that
short-term inhibition of ET receptors attenuates the coronary
epicardial vasoconstrictor response to acetylcholine in experimental
hypercholesterolemia. ET-1 (group I, n=5; 5
ng · kg-1 · min-1) and
acetylcholine (group III, n=7; 10-6 to 10-4
mol/L) were given by intracoronary infusion in pigs. ET-1 and
acetylcholine were also infused with the specific ETA-receptor blocker
FR-139317 (5 µg · kg-1 ·
min-1; group II, n=6; group IV, n=6). Acetylcholine was
also infused with the combined ET-receptor blocker, bosentan (0.5 mg/kg
plus 1 mg · kg-1 · h-1, group
V, n=5). The ETB-receptor agonist sarafotoxin 6c (5 ng ·
kg-1 · min-1; n=4) was also infused.
The percentage change in coronary artery diameter (%
CAD) to
the infusions was measured at baseline and after 10 weeks of
high-cholesterol diet in all animals. Sarafotoxin 6c mildly
reduced %CAD at baseline and 10 weeks (-10±2% and -12±3%,
respectively). FR-139317 did not attenuate the epicardial
vasoconstrictor response to ET-1 at baseline (%CAD -18±8% for
group I versus -12±6% for group II; P=NS) but did at
10 weeks (%CAD -77±14% for group I versus -14±6% for group
II; P<.05). FR-139317 did not affect the response to
acetylcholine at baseline (%CAD 5±2% for group III versus 7±3%
for group IV, P=NS) or at 10 weeks (%CAD -23±12%
for group III versus -19±7% for group IV; P=NS).
Bosentan did not affect the response to acetylcholine at baseline or 10
weeks. Short-term ET-receptor inhibition in experimental
hypercholesterolemia attenuated the enhanced
coronary epicardial vasoconstrictor effects of ET-1 but not
acetylcholine-induced coronary epicardial vasoconstriction,
suggesting that acetylcholine-induced coronary epicardial
vasoconstriction may not be mediated by ET receptors.
Key Words: pig • hypercholesterolemia • acetylcholine • endothelin • endothelin receptor
This article has been cited by other articles:
 |
|
 |
|
  P. Verhamme, R. Quarck, H. Hao, M. Knaapen, S. Dymarkowski, H. Bernar, J. Van Cleemput, S. Janssens, J. Vermylen, G. Gabbiani, et al. Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs Cardiovasc Res, October 1, 2002; 56(1): 135 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V Agapitov and W. G Haynes Role of endothelin in cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 1 - 15. [Abstract] [PDF]
|
|
|
|
 |
|
 S. H. Wilson, J. Herrmann, L. O. Lerman, D. R. Holmes Jr, C. Napoli, E. L. Ritman, and A. Lerman Simvastatin Preserves the Structure of Coronary Adventitial Vasa Vasorum in Experimental Hypercholesterolemia Independent of Lipid Lowering Circulation, January 29, 2002; 105(4): 415 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Matsumoto, R. Morishita, A. Moriguchi, N. Tomita, M. Aoki, H. Sakonjo, K. Matsumoto, T. Nakamura, J. Higaki, and T. Ogihara Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model Hypertension, February 1, 2001; 37(2): 270 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Wilson, R. D. Simari, P. J. M. Best, T. E. Peterson, L. O. Lerman, M. Aviram, K. A. Nath, D. R. Holmes Jr, and A. Lerman Simvastatin Preserves Coronary Endothelial Function in Hypercholesterolemia in the Absence of Lipid Lowering Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 122 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Wilson, P. J.M. Best, L. O. Lerman, D. R. Holmes Jr., D. M. Richardson, and A. Lerman Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandinF2{alpha}, in experimental hypercholesterolemia Cardiovasc Res, December 1, 1999; 44(3): 601 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. M. Best, L. O. Lerman, J. C. Romero, D. Richardson, D. R. Holmes Jr, and A. Lerman Coronary Endothelial Function Is Preserved With Chronic Endothelin Receptor Antagonism in Experimental Hypercholesterolemia In Vitro Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2769 - 2775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hasdai, M. F. Nielsen, R. A. Rizza, D. R. Holmes Jr, D. M. Richardson, P. Cohen, and A. Lerman Attenuated In Vitro Coronary Arteriolar Vasorelaxation to Insulin-like Growth Factor I in Experimental Hypercholesterolemia Hypertension, July 1, 1999; 34(1): 89 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. M. Best, C. J. McKenna, D. Hasdai, D. R. Holmes Jr, and A. Lerman Chronic Endothelin Receptor Antagonism Preserves Coronary Endothelial Function in Experimental Hypercholesterolemia Circulation, April 6, 1999; 99(13): 1747 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P.J. Halcox, K. R.A. Nour, G. Zalos, and A. A. Quyyumi Coronary Vasodilation and Improvement in Endothelial Dysfunction With Endothelin ETA Receptor Blockade Circ. Res., November 23, 2001; 89(11): 969 - 976. [Abstract] [Full Text] [PDF]
|
|