These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cardiovascular actions of ET-B activation in vivo and modulation by receptor antagonism.
    Author: Rasmussen TE, Jougasaki M, Supaporn T, Hallett JW, Brooks DP, Burnett JC.
    Journal: Am J Physiol; 1998 Jan; 274(1):R131-8. PubMed ID: 9458909.
    Abstract:
    The endothelin (ET)-B receptor subtype is expressed on vascular endothelial and smooth muscle cells and participates in vasodilatation and vasoconstriction. Controversy exists regarding the role of the ET-B receptor as a mediator of systemic, pulmonary, and renal vasoconstriction in states of marked ET-1 activation. Moreover, the potential activation of endogenous ET-1 with secondary stimulation of the ET-A receptor in response to sarafotoxin S6c (S6c) remains unclear. This study was designed to assess the cardiovascular actions of ET-B activation with S6c in the presence and absence of selective ET-A antagonism with FR-139317 and dual ET-A/ET-B antagonism with SB-209670 in the anesthetized dog. Compared with time control (n = 5), S6c increased from baseline systemic vascular resistance (SVR) [28 +/- 7 vs. 14 +/- 3 resistance units (RU), P < 0.05] and pulmonary vascular resistance (PVR) (3.2 +/- 0.7 vs. 0.9 +/- 0.3 RU, P < 0.05) and decreased cardiac output (CO) (-1.7 +/- 0.3 vs. -0.5 +/- 0.1 l/min, P < 0.05), with no differences in renal vascular resistance in association with increases in plasma ET-1. S6c also decreased mixed venous oxygen saturation (SVO2) (56 +/- 6 vs. 76 +/- 5%, P < 0.05). Selective ET-A receptor antagonism did not affect the actions of S6c, with the exception that ET-A receptor antagonism blocked the increase in SVR to high-dose S6c. Dual ET-A/ET-B receptor antagonism attenuated the increase from baseline in SVR (7 +/- 1 vs. 28 +/- 7 RU, P < 0.05) and PVR (0.7 +/- 0.2 vs. 3.2 +/- 0.7 RU, P < 0.05) and decrease from baseline in CO (-0.9 +/- 0.1 vs. -1.7 +/- 0.3 l/min, P < 0.05) and SVO2 (-7 +/- 3 vs. -20 +/- 3%, P < 0.05) observed with S6c alone. In summary, this study demonstrates an important role of ET-B receptor activation in vivo, which results in increases in plasma ET-1 and systemic and pulmonary vasoconstriction and reductions in CO and SVO2. This study also supports a modest role for the ET-A receptor in mediating the systemic vasoconstrictor response to high-dose S6c.
    [Abstract] [Full Text] [Related] [New Search]