Tags

Type your tag names separated by a space and hit enter

Differential distribution of angiotensin AT2 receptors in the normal and failing human heart.
J Pharmacol Exp Ther. 1998 Jan; 284(1):323-36.JP

Abstract

Cardiac expression of angiotensin II (Ang II) AT1 and AT2 receptor subtypes is species dependent, and changes in their relative proportion may influence myocardial hypertrophy and fibrosis. Regional differences in the distribution of Ang II receptors in the normal and failing human heart were assessed using 125I-(Sar1,Ile8)Ang II binding and quantitative autoradiography. Receptor subtypes were distinguished by their affinity for selective nonpeptide antagonists (losartan and PD123319) and sensitivity to dithiothreitol. Ventricular and atrial tissues displayed a heterogeneous distribution of ligand binding sites. AT2 receptors predominated, representing 70% to 77% of the sites in normal and noninfarcted myocardium. Endocardial, interstitial, perivascular and infarcted regions in the ventricles of patients with end-stage ischemic heart disease or dilated cardiomyopathy exhibited a significantly greater density (P < .001) of high affinity AT2 binding sites (Kd = 0.57 nmol/liter) compared with adjacent noninfarcted myocardium. Regions displaying the relative increase in AT2 binding sites corresponded to areas of fibroblast proliferation and collagen deposition, shown by picrosirius red staining. AT1 binding sites were localized to nerves, occurred at relatively low density in coronary vessels and represented only 23% to 29% of myocardial 125I-(Sar1,Ile8)Ang II binding sites. The border zone between infarcted and noninfarcted myocardium characteristically contained numerous microvessels, exhibiting perivascular AT2 receptors and endothelial angiotensin converting enzyme activity, as demonstrated by binding of 125I-351A. Specific myocardial AT2 receptor mRNA transcripts (approximately 3 kb) were identified and exhibited alternative splicing of untranslated 5' exons. The differential distribution of cardiac Ang II receptor subtypes and selective increase in binding to AT2 sites in the diseased heart suggest that cells bearing the AT2 receptor represent a significant target for Ang II, possibly contributing to its growth-related actions.

Authors+Show Affiliations

Department of Histochemistry, Imperial College School of Medicine, Hammersmith Hospital, London, UK. jwharton@rpms.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9435195

Citation

Wharton, J, et al. "Differential Distribution of Angiotensin AT2 Receptors in the Normal and Failing Human Heart." The Journal of Pharmacology and Experimental Therapeutics, vol. 284, no. 1, 1998, pp. 323-36.
Wharton J, Morgan K, Rutherford RA, et al. Differential distribution of angiotensin AT2 receptors in the normal and failing human heart. J Pharmacol Exp Ther. 1998;284(1):323-36.
Wharton, J., Morgan, K., Rutherford, R. A., Catravas, J. D., Chester, A., Whitehead, B. F., De Leval, M. R., Yacoub, M. H., & Polak, J. M. (1998). Differential distribution of angiotensin AT2 receptors in the normal and failing human heart. The Journal of Pharmacology and Experimental Therapeutics, 284(1), 323-36.
Wharton J, et al. Differential Distribution of Angiotensin AT2 Receptors in the Normal and Failing Human Heart. J Pharmacol Exp Ther. 1998;284(1):323-36. PubMed PMID: 9435195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential distribution of angiotensin AT2 receptors in the normal and failing human heart. AU - Wharton,J, AU - Morgan,K, AU - Rutherford,R A, AU - Catravas,J D, AU - Chester,A, AU - Whitehead,B F, AU - De Leval,M R, AU - Yacoub,M H, AU - Polak,J M, PY - 1998/1/22/pubmed PY - 1998/1/22/medline PY - 1998/1/22/entrez SP - 323 EP - 36 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 284 IS - 1 N2 - Cardiac expression of angiotensin II (Ang II) AT1 and AT2 receptor subtypes is species dependent, and changes in their relative proportion may influence myocardial hypertrophy and fibrosis. Regional differences in the distribution of Ang II receptors in the normal and failing human heart were assessed using 125I-(Sar1,Ile8)Ang II binding and quantitative autoradiography. Receptor subtypes were distinguished by their affinity for selective nonpeptide antagonists (losartan and PD123319) and sensitivity to dithiothreitol. Ventricular and atrial tissues displayed a heterogeneous distribution of ligand binding sites. AT2 receptors predominated, representing 70% to 77% of the sites in normal and noninfarcted myocardium. Endocardial, interstitial, perivascular and infarcted regions in the ventricles of patients with end-stage ischemic heart disease or dilated cardiomyopathy exhibited a significantly greater density (P < .001) of high affinity AT2 binding sites (Kd = 0.57 nmol/liter) compared with adjacent noninfarcted myocardium. Regions displaying the relative increase in AT2 binding sites corresponded to areas of fibroblast proliferation and collagen deposition, shown by picrosirius red staining. AT1 binding sites were localized to nerves, occurred at relatively low density in coronary vessels and represented only 23% to 29% of myocardial 125I-(Sar1,Ile8)Ang II binding sites. The border zone between infarcted and noninfarcted myocardium characteristically contained numerous microvessels, exhibiting perivascular AT2 receptors and endothelial angiotensin converting enzyme activity, as demonstrated by binding of 125I-351A. Specific myocardial AT2 receptor mRNA transcripts (approximately 3 kb) were identified and exhibited alternative splicing of untranslated 5' exons. The differential distribution of cardiac Ang II receptor subtypes and selective increase in binding to AT2 sites in the diseased heart suggest that cells bearing the AT2 receptor represent a significant target for Ang II, possibly contributing to its growth-related actions. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9435195/Differential_distribution_of_angiotensin_AT2_receptors_in_the_normal_and_failing_human_heart_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=9435195 DB - PRIME DP - Unbound Medicine ER -