Tags

Type your tag names separated by a space and hit enter

Predominance of AT(1) blockade over mas-mediated angiotensin-(1-7) mechanisms in the regulation of blood pressure and renin-angiotensin system in mRen2.Lewis rats.
Am J Hypertens. 2013 May; 26(5):583-90.AJ

Abstract

BACKGROUND

We investigated whether the antihypertensive actions of the angiotensin II (Ang II) receptor (AT(1)-R) blocker, olmesartan medoxomil, may in part be mediated by increased Ang-(1-7) in the absence of significant changes in plasma Ang II.

METHODS

mRen2.Lewis congenic hypertensive rats were administered either a vehicle (n = 14) or olmesartan (0.5 mg/kg/day; n = 14) by osmotic minipumps. Two weeks later, rats from both groups were further randomized to receive either the mas receptor antagonist A-779 (0.5 mg/kg/day; n = 7 per group) or its vehicle (n = 7 per group) for the next 4 weeks. Blood pressure was monitored by telemetry, and circulating and tissue components of the renin-angiotensin system (RAS) were measured at the completion of the experiments.

RESULTS

Antihypertensive effects of olmesartan were associated with an increase in plasma renin concentration, plasma Ang I, Ang II, and Ang-(1-7), whereas serum aldosterone levels and kidney Ang II content were reduced. Preserved Ang-(1-7) content in kidneys was associated with increases of ACE2 protein but not activity and no changes on serum and kidney ACE activity. There was no change in cardiac peptide levels after olmesartan treatment. The antihypertensive effects of olmesartan were not altered by concomitant administration of the Ang-(1-7) receptor antagonist except for a mild further increase in plasma renin concentration.

CONCLUSIONS

Our study highlights the independent regulation of RAS among plasma, heart, and kidney tissue in response to AT(1)-R blockade. Ang-(1-7) through the mas receptor does not mediate long-term effects of olmesartan besides counterbalancing renin release in response to AT(1)-R blockade.

Authors+Show Affiliations

Hypertension and Vascular Research Center, Wake Forest University, Winston-Salem, NC, USA. jvaragic@wfubmc.eduNo 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, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23459599

Citation

Varagic, Jasmina, et al. "Predominance of AT(1) Blockade Over Mas-mediated Angiotensin-(1-7) Mechanisms in the Regulation of Blood Pressure and Renin-angiotensin System in mRen2.Lewis Rats." American Journal of Hypertension, vol. 26, no. 5, 2013, pp. 583-90.
Varagic J, Ahmad S, VonCannon JL, et al. Predominance of AT(1) blockade over mas-mediated angiotensin-(1-7) mechanisms in the regulation of blood pressure and renin-angiotensin system in mRen2.Lewis rats. Am J Hypertens. 2013;26(5):583-90.
Varagic, J., Ahmad, S., VonCannon, J. L., Moniwa, N., Brosnihan, K. B., Wysocki, J., Batlle, D., & Ferrario, C. M. (2013). Predominance of AT(1) blockade over mas-mediated angiotensin-(1-7) mechanisms in the regulation of blood pressure and renin-angiotensin system in mRen2.Lewis rats. American Journal of Hypertension, 26(5), 583-90. https://doi.org/10.1093/ajh/hps090
Varagic J, et al. Predominance of AT(1) Blockade Over Mas-mediated Angiotensin-(1-7) Mechanisms in the Regulation of Blood Pressure and Renin-angiotensin System in mRen2.Lewis Rats. Am J Hypertens. 2013;26(5):583-90. PubMed PMID: 23459599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predominance of AT(1) blockade over mas-mediated angiotensin-(1-7) mechanisms in the regulation of blood pressure and renin-angiotensin system in mRen2.Lewis rats. AU - Varagic,Jasmina, AU - Ahmad,Sarfaraz, AU - VonCannon,Jessica L, AU - Moniwa,Norihito, AU - Brosnihan,K Bridget, AU - Wysocki,Jan, AU - Batlle,Daniel, AU - Ferrario,Carlos M, Y1 - 2013/03/04/ PY - 2013/3/6/entrez PY - 2013/3/6/pubmed PY - 2013/9/24/medline SP - 583 EP - 90 JF - American journal of hypertension JO - Am J Hypertens VL - 26 IS - 5 N2 - BACKGROUND: We investigated whether the antihypertensive actions of the angiotensin II (Ang II) receptor (AT(1)-R) blocker, olmesartan medoxomil, may in part be mediated by increased Ang-(1-7) in the absence of significant changes in plasma Ang II. METHODS: mRen2.Lewis congenic hypertensive rats were administered either a vehicle (n = 14) or olmesartan (0.5 mg/kg/day; n = 14) by osmotic minipumps. Two weeks later, rats from both groups were further randomized to receive either the mas receptor antagonist A-779 (0.5 mg/kg/day; n = 7 per group) or its vehicle (n = 7 per group) for the next 4 weeks. Blood pressure was monitored by telemetry, and circulating and tissue components of the renin-angiotensin system (RAS) were measured at the completion of the experiments. RESULTS: Antihypertensive effects of olmesartan were associated with an increase in plasma renin concentration, plasma Ang I, Ang II, and Ang-(1-7), whereas serum aldosterone levels and kidney Ang II content were reduced. Preserved Ang-(1-7) content in kidneys was associated with increases of ACE2 protein but not activity and no changes on serum and kidney ACE activity. There was no change in cardiac peptide levels after olmesartan treatment. The antihypertensive effects of olmesartan were not altered by concomitant administration of the Ang-(1-7) receptor antagonist except for a mild further increase in plasma renin concentration. CONCLUSIONS: Our study highlights the independent regulation of RAS among plasma, heart, and kidney tissue in response to AT(1)-R blockade. Ang-(1-7) through the mas receptor does not mediate long-term effects of olmesartan besides counterbalancing renin release in response to AT(1)-R blockade. SN - 1941-7225 UR - https://www.unboundmedicine.com/medline/citation/23459599/Predominance_of_AT_1__blockade_over_mas_mediated_angiotensin__1_7__mechanisms_in_the_regulation_of_blood_pressure_and_renin_angiotensin_system_in_mRen2_Lewis_rats_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1093/ajh/hps090 DB - PRIME DP - Unbound Medicine ER -