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Analysis of responses to big endothelin in the hindquarters vascular bed of the cat.

Publication ,  Journal Article
Tamura, DY; Minkes, RK; Bellan, JA; McMahon, TJ; McNamara, DB; Kadowitz, PJ
Published in: Can J Cardiol
November 1992

OBJECTIVE: To investigate vascular responses to the endothelin-1 (ET-1) precursor, human big endothelin 1-38 (big ET), in the peripheral vascular bed of the cat. DESIGN: These studies were designed to investigate the hypothesis that bit ET is converted to an active peptide with properties similar to ET-1. SETTING: Hindquarters vascular bed of the cat under conditions of controlled bloodflow; changes in perfusion pressure reflect changes in vascular resistance. ANIMALS: Fifty-four adult mongrel cats. INTERVENTIONS: Big ET, ET-1, the peptidases chymotrypsin, pepsin and cathepsin-D, and the metalloprotease inhibitor phosphoramidon. MAIN RESULTS: Intra-arterial injections of big ET induced a slow-developing and sustained increase in hindquarters perfusion pressure which could be blocked by phosphoramidon. ET-1 (0.3 nmol), administered as a slow infusion over a 10-min period, produced a slowly developing increase in hindquarters perfusion pressure in a manner similar to that observed in response to injection of big ET. A bolus injection of ET-1 produced a biphasic response characterized by a transient decrease in pressure followed by an increase which was significantly greater in magnitude and more rapid in onset than the pressor response to big ET (0.3 nmol). After incubation of big ET with chymotrypsin, pepsin and cathepsin-D (each 5% weight/weight) for 30 mins at 37 degrees C, injection of activated big ET produced a biphasic response characteristic of the response to ET-1 with an initial transient decrease in pressure followed by a secondary increase in hindquarters perfusion pressure. CONCLUSIONS: Big ET produces a phosphoramidon-sensitive pressor response which is similar to that produced by an infusion of ET-1. These data suggest that chymotrypsin, pepsin and cathepsin-D can convert big ET to an active peptide which elicits a biphasic response similar to that produced by ET-1.

Duke Scholars

Published In

Can J Cardiol

ISSN

0828-282X

Publication Date

November 1992

Volume

8

Issue

9

Start / End Page

954 / 960

Location

England

Related Subject Headings

  • Regional Blood Flow
  • Protein Precursors
  • Pepsin A
  • Neprilysin
  • Injections, Intra-Arterial
  • Infusions, Intra-Arterial
  • Hindlimb
  • Glycopeptides
  • Endothelins
  • Endothelin-1
 

Citation

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Tamura, D. Y., Minkes, R. K., Bellan, J. A., McMahon, T. J., McNamara, D. B., & Kadowitz, P. J. (1992). Analysis of responses to big endothelin in the hindquarters vascular bed of the cat. Can J Cardiol, 8(9), 954–960.
Tamura, D. Y., R. K. Minkes, J. A. Bellan, T. J. McMahon, D. B. McNamara, and P. J. Kadowitz. “Analysis of responses to big endothelin in the hindquarters vascular bed of the cat.Can J Cardiol 8, no. 9 (November 1992): 954–60.
Tamura DY, Minkes RK, Bellan JA, McMahon TJ, McNamara DB, Kadowitz PJ. Analysis of responses to big endothelin in the hindquarters vascular bed of the cat. Can J Cardiol. 1992 Nov;8(9):954–60.
Tamura, D. Y., et al. “Analysis of responses to big endothelin in the hindquarters vascular bed of the cat.Can J Cardiol, vol. 8, no. 9, Nov. 1992, pp. 954–60.
Tamura DY, Minkes RK, Bellan JA, McMahon TJ, McNamara DB, Kadowitz PJ. Analysis of responses to big endothelin in the hindquarters vascular bed of the cat. Can J Cardiol. 1992 Nov;8(9):954–960.
Journal cover image

Published In

Can J Cardiol

ISSN

0828-282X

Publication Date

November 1992

Volume

8

Issue

9

Start / End Page

954 / 960

Location

England

Related Subject Headings

  • Regional Blood Flow
  • Protein Precursors
  • Pepsin A
  • Neprilysin
  • Injections, Intra-Arterial
  • Infusions, Intra-Arterial
  • Hindlimb
  • Glycopeptides
  • Endothelins
  • Endothelin-1