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Modulation of renal glomerular angiotensin II receptors by ace inhibition and AT1 receptor antagonism.
Regul Pept. 1997 Jan 29; 68(2):111-7.RP

Abstract

Angiotensin-converting enzyme inhibitors (ACE-I) and specific nonpeptide angiotensin II (ANG II) receptor antagonists have been used extensively to treat a variety of cardiovascular disorders in experimental animals and humans. Despite their widespread use, only a limited amount of data has been published regarding the effect that renin-angiotensin system (RAS) blockade may have on ANG II receptors, and very often this information is contradictory. The present study was designed to investigate whether changes in plasma ANG II levels induced by RAS blockade could alter glomerular ANG II receptor characteristics. Captopril was employed as an ACE-I with losartan and TCV-116, two AT1 receptor antagonists of different chemical structure. Two experimental protocols were established. Protocol 1 contained 3 experimental groups: controls (Sprague-Dawley rats, 250-300 g BW), and animals treated with either captopril (0.5 g/l via drinking water) or losartan (10 mg/kg BW p.o.). In protocol 2, the animals were treated as in protocol 1 except that losartan was replaced by TCV-116 (1 mg/kg BW p.o.). At the end of treatment (3 days), all groups were killed by decapitation, blood was collected for plasma renin activity (PRA) measurement, and hearts and kidneys were excised. ANG II receptors were assessed by radioligand binding assays on membrane preparations of purified glomeruli, by displacement of 125I-[Sar1, Ile8]-ANG II with specific nonpeptide antagonists of AT1 (losartan) and AT2 (PD 123319) receptor subtypes. RAS blockade by either ACE-I or AT1 antagonists increased PRA. The binding assays showed that renal glomeruli from treated rats and controls expressed a single population (AT1) of ANG II receptors. The density of glomerular AT1 receptors was not modulated by captopril, but was significantly lower in animals treated with either losartan (Bmax: 854 +/- 169 vs. 379 +/- 79 fmol/mg protein and Kd: 59 +/- 6 vs. 45 +/- 6 nM for controls and losartan, respectively) or TCV-116 (480 +/- 72 vs. 188 +/- 16 fmol/mg protein and Kd: 45 +/- 9 vs. 37 +/- 18 nM for controls and TCV-116, respectively) than in their controls. No changes in receptor affinity (Kd) were detected. Previous membrane "acid-wash" did not modify the results. We conclude that short-term RAS blockade by AT1 antagonists, but not by ACE-I, induces true downregulation of renal glomerular ANG II receptors. No AT2 receptor subtype was detected.

Authors+Show Affiliations

Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9110382

Citation

Haddad, G, et al. "Modulation of Renal Glomerular Angiotensin II Receptors By Ace Inhibition and AT1 Receptor Antagonism." Regulatory Peptides, vol. 68, no. 2, 1997, pp. 111-7.
Haddad G, Amiri F, Garcia R. Modulation of renal glomerular angiotensin II receptors by ace inhibition and AT1 receptor antagonism. Regul Pept. 1997;68(2):111-7.
Haddad, G., Amiri, F., & Garcia, R. (1997). Modulation of renal glomerular angiotensin II receptors by ace inhibition and AT1 receptor antagonism. Regulatory Peptides, 68(2), 111-7.
Haddad G, Amiri F, Garcia R. Modulation of Renal Glomerular Angiotensin II Receptors By Ace Inhibition and AT1 Receptor Antagonism. Regul Pept. 1997 Jan 29;68(2):111-7. PubMed PMID: 9110382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of renal glomerular angiotensin II receptors by ace inhibition and AT1 receptor antagonism. AU - Haddad,G, AU - Amiri,F, AU - Garcia,R, PY - 1997/1/29/pubmed PY - 1997/1/29/medline PY - 1997/1/29/entrez SP - 111 EP - 7 JF - Regulatory peptides JO - Regul. Pept. VL - 68 IS - 2 N2 - Angiotensin-converting enzyme inhibitors (ACE-I) and specific nonpeptide angiotensin II (ANG II) receptor antagonists have been used extensively to treat a variety of cardiovascular disorders in experimental animals and humans. Despite their widespread use, only a limited amount of data has been published regarding the effect that renin-angiotensin system (RAS) blockade may have on ANG II receptors, and very often this information is contradictory. The present study was designed to investigate whether changes in plasma ANG II levels induced by RAS blockade could alter glomerular ANG II receptor characteristics. Captopril was employed as an ACE-I with losartan and TCV-116, two AT1 receptor antagonists of different chemical structure. Two experimental protocols were established. Protocol 1 contained 3 experimental groups: controls (Sprague-Dawley rats, 250-300 g BW), and animals treated with either captopril (0.5 g/l via drinking water) or losartan (10 mg/kg BW p.o.). In protocol 2, the animals were treated as in protocol 1 except that losartan was replaced by TCV-116 (1 mg/kg BW p.o.). At the end of treatment (3 days), all groups were killed by decapitation, blood was collected for plasma renin activity (PRA) measurement, and hearts and kidneys were excised. ANG II receptors were assessed by radioligand binding assays on membrane preparations of purified glomeruli, by displacement of 125I-[Sar1, Ile8]-ANG II with specific nonpeptide antagonists of AT1 (losartan) and AT2 (PD 123319) receptor subtypes. RAS blockade by either ACE-I or AT1 antagonists increased PRA. The binding assays showed that renal glomeruli from treated rats and controls expressed a single population (AT1) of ANG II receptors. The density of glomerular AT1 receptors was not modulated by captopril, but was significantly lower in animals treated with either losartan (Bmax: 854 +/- 169 vs. 379 +/- 79 fmol/mg protein and Kd: 59 +/- 6 vs. 45 +/- 6 nM for controls and losartan, respectively) or TCV-116 (480 +/- 72 vs. 188 +/- 16 fmol/mg protein and Kd: 45 +/- 9 vs. 37 +/- 18 nM for controls and TCV-116, respectively) than in their controls. No changes in receptor affinity (Kd) were detected. Previous membrane "acid-wash" did not modify the results. We conclude that short-term RAS blockade by AT1 antagonists, but not by ACE-I, induces true downregulation of renal glomerular ANG II receptors. No AT2 receptor subtype was detected. SN - 0167-0115 UR - https://www.unboundmedicine.com/medline/citation/9110382/Modulation_of_renal_glomerular_angiotensin_II_receptors_by_ace_inhibition_and_AT1_receptor_antagonism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-0115(96)02112-X DB - PRIME DP - Unbound Medicine ER -