Tags

Type your tag names separated by a space and hit enter

Enhanced endothelin(A) receptor-mediated calcium mobilization and contraction in organ cultured porcine coronary arteries.
J Pharmacol Exp Ther. 2000 Nov; 295(2):484-91.JP

Abstract

Arterial injury models for coronary artery disease have demonstrated an enhanced expression and function of either the endothelin(A) or endothelin(B) (ET(A) or ET(B)) receptor subtype. We hypothesized that organ culture would enhance the physiological function of ET receptors in the porcine right coronary artery. Arteries were either cold stored (4 degrees C) or organ cultured (37 degrees C) for 4 days. After 4 days, the artery was either 1) sectioned into rings to measure the ET-1-induced isometric tension response (3 x 10(-10)-3 x 10(-7) M), or 2) enzymatically dispersed and the isolated smooth muscle cells imaged using fura-2 to measure the myoplasmic calcium (Ca(m)) response to 3 x 10(-8) M ET-1 (approximately EC(50)). Isometric tension and Ca(m) to ET-1 were measured in the absence and presence of bosentan (nonselective ET(A) or ET(B) receptor antagonist), BQ788 (ET(B)-selective antagonist), and BQ123 (ET(A)-selective antagonist). Compared with cold storage, organ culture induced a 2-fold increase in tension development (3 x 10(-7) M ET-1) and Ca(m) (3 x 10(-8) M ET-1), which was inhibited with bosentan, thus confirming the enhanced responses to ET-1 were due to ET receptor activation. BQ123 also inhibited the enhanced contraction and Ca(m) responses to ET-1. In contrast, BQ788 failed to inhibit tension development and Ca(m) responses to ET-1 in organ culture and cold storage. Sarafotoxin 6C (ET(B) agonist) failed to elicit an increased Ca(m) response in organ culture compared with cold storage. Our results indicate the increased tension development and Ca(m) responses to ET-1 in organ culture are attributable to ET(A) receptors, and not ET(B) receptors.

Authors+Show Affiliations

Vascular Biology Laboratory, Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11046079

Citation

Hill, B J., et al. "Enhanced endothelin(A) Receptor-mediated Calcium Mobilization and Contraction in Organ Cultured Porcine Coronary Arteries." The Journal of Pharmacology and Experimental Therapeutics, vol. 295, no. 2, 2000, pp. 484-91.
Hill BJ, Katwa LC, Wamhoff BR, et al. Enhanced endothelin(A) receptor-mediated calcium mobilization and contraction in organ cultured porcine coronary arteries. J Pharmacol Exp Ther. 2000;295(2):484-91.
Hill, B. J., Katwa, L. C., Wamhoff, B. R., & Sturek, M. (2000). Enhanced endothelin(A) receptor-mediated calcium mobilization and contraction in organ cultured porcine coronary arteries. The Journal of Pharmacology and Experimental Therapeutics, 295(2), 484-91.
Hill BJ, et al. Enhanced endothelin(A) Receptor-mediated Calcium Mobilization and Contraction in Organ Cultured Porcine Coronary Arteries. J Pharmacol Exp Ther. 2000;295(2):484-91. PubMed PMID: 11046079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced endothelin(A) receptor-mediated calcium mobilization and contraction in organ cultured porcine coronary arteries. AU - Hill,B J, AU - Katwa,L C, AU - Wamhoff,B R, AU - Sturek,M, PY - 2000/10/25/pubmed PY - 2001/2/28/medline PY - 2000/10/25/entrez SP - 484 EP - 91 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 295 IS - 2 N2 - Arterial injury models for coronary artery disease have demonstrated an enhanced expression and function of either the endothelin(A) or endothelin(B) (ET(A) or ET(B)) receptor subtype. We hypothesized that organ culture would enhance the physiological function of ET receptors in the porcine right coronary artery. Arteries were either cold stored (4 degrees C) or organ cultured (37 degrees C) for 4 days. After 4 days, the artery was either 1) sectioned into rings to measure the ET-1-induced isometric tension response (3 x 10(-10)-3 x 10(-7) M), or 2) enzymatically dispersed and the isolated smooth muscle cells imaged using fura-2 to measure the myoplasmic calcium (Ca(m)) response to 3 x 10(-8) M ET-1 (approximately EC(50)). Isometric tension and Ca(m) to ET-1 were measured in the absence and presence of bosentan (nonselective ET(A) or ET(B) receptor antagonist), BQ788 (ET(B)-selective antagonist), and BQ123 (ET(A)-selective antagonist). Compared with cold storage, organ culture induced a 2-fold increase in tension development (3 x 10(-7) M ET-1) and Ca(m) (3 x 10(-8) M ET-1), which was inhibited with bosentan, thus confirming the enhanced responses to ET-1 were due to ET receptor activation. BQ123 also inhibited the enhanced contraction and Ca(m) responses to ET-1. In contrast, BQ788 failed to inhibit tension development and Ca(m) responses to ET-1 in organ culture and cold storage. Sarafotoxin 6C (ET(B) agonist) failed to elicit an increased Ca(m) response in organ culture compared with cold storage. Our results indicate the increased tension development and Ca(m) responses to ET-1 in organ culture are attributable to ET(A) receptors, and not ET(B) receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11046079/Enhanced_endothelin_A__receptor_mediated_calcium_mobilization_and_contraction_in_organ_cultured_porcine_coronary_arteries_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11046079 DB - PRIME DP - Unbound Medicine ER -