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Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts.

Publication ,  Journal Article
Lopez, JJ; Lorell, BH; Ingelfinger, JR; Weinberg, EO; Schunkert, H; Diamant, D; Tang, SS
Published in: Am J Physiol
August 1994

To determine distribution and function of cardiac angiotensin (ANG) II receptor AT1 and AT2 subtypes in left ventricular (LV) hypertrophy (LVH), ANG II (10(-8) M) was infused into isolated rat hearts with hypertrophy from aortic banding and into sham-operated controls. ANG II was infused alone or in the presence of AT1 inhibitor [losartan (10(-5) M) or CL-329167 (10(-7) M)] or AT2 inhibitor [CG-42112A (10(-8) M]. ANG II alone caused less increase in coronary vascular resistance (CVR) in LVH compared with control hearts (19 vs. 39%; P < 0.01), although baseline CVR was higher in LVH hearts. This was prevented by AT1 but not AT2 antagonists. ANG II also increased LV end-diastolic pressure in LVH hearts, signifying decreased diastolic relaxation that was prevented by AT1 but not AT2 inhibition. Characterization of ANG II binding sites in LV membrane preparations revealed similar dissociation constants between groups (1.6 +/- 0.95 vs. 2.2 +/- 2.0 nM; not significant) but lower maximum binding capacity in the LVH group (21.1 +/- 5.9 vs. 33.5 +/- 3.0 fmol/mg protein; P < 0.05). Competition assays demonstrated that control left ventricles contain predominantly the AT1 subtype (68.8 +/- 20%), whereas LVH ventricles contain primarily the putative AT2 subtype (59.8% +/- 10.8%; P < 0.05). This suggests that receptor subtype redistribution occurs in LVH with AT1 subtype down-regulation. Nonetheless, the AT1 subtype mediates the effects of ANG II on coronary tone and diastolic dysfunction in pressure-overload hypertrophy.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

August 1994

Volume

267

Issue

2 Pt 2

Start / End Page

H844 / H852

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Tetrazoles
  • Reference Values
  • Receptors, Angiotensin
  • Rats, Wistar
  • Rats
  • Pyridines
  • Myocardium
  • Male
  • Losartan
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lopez, J. J., Lorell, B. H., Ingelfinger, J. R., Weinberg, E. O., Schunkert, H., Diamant, D., & Tang, S. S. (1994). Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts. Am J Physiol, 267(2 Pt 2), H844–H852. https://doi.org/10.1152/ajpheart.1994.267.2.H844
Lopez, J. J., B. H. Lorell, J. R. Ingelfinger, E. O. Weinberg, H. Schunkert, D. Diamant, and S. S. Tang. “Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts.Am J Physiol 267, no. 2 Pt 2 (August 1994): H844–52. https://doi.org/10.1152/ajpheart.1994.267.2.H844.
Lopez JJ, Lorell BH, Ingelfinger JR, Weinberg EO, Schunkert H, Diamant D, et al. Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts. Am J Physiol. 1994 Aug;267(2 Pt 2):H844–52.
Lopez, J. J., et al. “Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts.Am J Physiol, vol. 267, no. 2 Pt 2, Aug. 1994, pp. H844–52. Pubmed, doi:10.1152/ajpheart.1994.267.2.H844.
Lopez JJ, Lorell BH, Ingelfinger JR, Weinberg EO, Schunkert H, Diamant D, Tang SS. Distribution and function of cardiac angiotensin AT1- and AT2-receptor subtypes in hypertrophied rat hearts. Am J Physiol. 1994 Aug;267(2 Pt 2):H844–H852.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

August 1994

Volume

267

Issue

2 Pt 2

Start / End Page

H844 / H852

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Tetrazoles
  • Reference Values
  • Receptors, Angiotensin
  • Rats, Wistar
  • Rats
  • Pyridines
  • Myocardium
  • Male
  • Losartan