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Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia.
Arterioscler Thromb Vasc Biol. 1997 Nov; 17(11):2737-43.AT

Abstract

The coronary vasoconstrictor effects of endothelins, mediated by both endothelin ETA and ETB receptors, may be differentially altered in pathophysiological states associated with endothelial dysfunction and elevated endothelin levels. Experimental hypercholesterolemia is associated with coronary endothelial dysfunction and increased circulating endothelin concentrations. These studies were designed to test the hypothesis that experimental hypercholesterolemia is characterized by a differentially altered coronary contractile response to ETA- and ETB-receptor stimulation, in vitro. Pigs were fed either a normal or a high-cholesterol diet for 10 to 13 weeks. Changes in the intraluminal diameter of pressurized small coronary arteries (< 481 +/- 25 microns in diameter) to cumulative concentrations (10(-10) to 10(-6) mol/L) of endothelin-1 (ET-1), and sarafotoxin 6c (S6c), a specific ETB-receptor agonist, were measured using a video dimension analyzer. The maximal contraction attained with ET-1 was greater than with S6c in both normal (86 +/- 7% versus 47 +/- 7%, P = .001) and hypercholesterolemic (77 +/- 6% versus 37 +/- 7%, P < .001) pigs. At 10(-10) mol/L, vessels from hypercholesterolemic pigs manifested greater contraction to both ET-1 (23 +/- 6% versus 8 +/- 3%, P = .02) and S6c (17 +/- 5% versus 4 +/- 2%, P = .02). Incubation of arteries from hypercholesterolemic pigs with BQ-788 (ETB-receptor antagonist), but not FR-139317 (ETA-receptor antagonist), altered the contractile response to ET-1 at 10(-10) mol/L. Removal of the endothelium abolished the difference in response to S6c between normal and hypercholesterolemic pigs. These studies demonstrate that experimental hypercholesterolemia is characterized by enhanced coronary vasoconstriction to endothelins in vitro, the mechanism of which is mediated mainly through the ETB receptor. Thus, the ETB receptor has a role in regulation of coronary artery tone in both the steady-state and pathophysiological states.

Authors+Show Affiliations

Division of Internal Medicine and Cardiovascular Diseases, Mayo Clinic, Rochester, Minn. 55905, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9409250

Citation

Hasdai, D, et al. "Enhanced endothelin-B-receptor-mediated Vasoconstriction of Small Porcine Coronary Arteries in Diet-induced Hypercholesterolemia." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 11, 1997, pp. 2737-43.
Hasdai D, Mathew V, Schwartz RS, et al. Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1997;17(11):2737-43.
Hasdai, D., Mathew, V., Schwartz, R. S., Smith, L. A., Holmes, D. R., Katusic, Z. S., & Lerman, A. (1997). Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 17(11), 2737-43.
Hasdai D, et al. Enhanced endothelin-B-receptor-mediated Vasoconstriction of Small Porcine Coronary Arteries in Diet-induced Hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1997;17(11):2737-43. PubMed PMID: 9409250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia. AU - Hasdai,D, AU - Mathew,V, AU - Schwartz,R S, AU - Smith,L A, AU - Holmes,D R,Jr AU - Katusic,Z S, AU - Lerman,A, PY - 1997/12/31/pubmed PY - 2001/3/28/medline PY - 1997/12/31/entrez SP - 2737 EP - 43 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 17 IS - 11 N2 - The coronary vasoconstrictor effects of endothelins, mediated by both endothelin ETA and ETB receptors, may be differentially altered in pathophysiological states associated with endothelial dysfunction and elevated endothelin levels. Experimental hypercholesterolemia is associated with coronary endothelial dysfunction and increased circulating endothelin concentrations. These studies were designed to test the hypothesis that experimental hypercholesterolemia is characterized by a differentially altered coronary contractile response to ETA- and ETB-receptor stimulation, in vitro. Pigs were fed either a normal or a high-cholesterol diet for 10 to 13 weeks. Changes in the intraluminal diameter of pressurized small coronary arteries (< 481 +/- 25 microns in diameter) to cumulative concentrations (10(-10) to 10(-6) mol/L) of endothelin-1 (ET-1), and sarafotoxin 6c (S6c), a specific ETB-receptor agonist, were measured using a video dimension analyzer. The maximal contraction attained with ET-1 was greater than with S6c in both normal (86 +/- 7% versus 47 +/- 7%, P = .001) and hypercholesterolemic (77 +/- 6% versus 37 +/- 7%, P < .001) pigs. At 10(-10) mol/L, vessels from hypercholesterolemic pigs manifested greater contraction to both ET-1 (23 +/- 6% versus 8 +/- 3%, P = .02) and S6c (17 +/- 5% versus 4 +/- 2%, P = .02). Incubation of arteries from hypercholesterolemic pigs with BQ-788 (ETB-receptor antagonist), but not FR-139317 (ETA-receptor antagonist), altered the contractile response to ET-1 at 10(-10) mol/L. Removal of the endothelium abolished the difference in response to S6c between normal and hypercholesterolemic pigs. These studies demonstrate that experimental hypercholesterolemia is characterized by enhanced coronary vasoconstriction to endothelins in vitro, the mechanism of which is mediated mainly through the ETB receptor. Thus, the ETB receptor has a role in regulation of coronary artery tone in both the steady-state and pathophysiological states. SN - 1079-5642 UR - https://www.unboundmedicine.com/medline/citation/9409250/Enhanced_endothelin_B_receptor_mediated_vasoconstriction_of_small_porcine_coronary_arteries_in_diet_induced_hypercholesterolemia_ L2 - https://www.ahajournals.org/doi/10.1161/01.atv.17.11.2737?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -