Tags

Type your tag names separated by a space and hit enter

Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists.
Am J Hypertens. 2005 Apr; 18(4 Pt 1):493-9.AJ

Abstract

BACKGROUND

Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by Ang II type 1 (AT1) receptors. The effects of Ang II via the Ang II type 2 (AT2) receptor subtype (AT2R) are less well defined. Growing evidence shows the existence of cross-talk between the Ang II receptor subtypes, which is revealed by AT1R blockade. Hence, under certain conditions, AT2R may act as an antagonistic system with respect to the AT1R.

METHODS

The present study was designed to investigate the effects of long-term treatment with the AT1R antagonist losartan on the AT2R-mediated response to Ang II in thoracic aortas isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Untreated animals from both groups were used as controls. The mRNA expression of AT1R and AT2R was measured by reverse transcription-polymerase chain reaction.

RESULTS

During contraction in response to norepinephrine, Ang II induced concentration-dependent relaxation only in aortas isolated from SHR chronically treated with losartan (8 weeks; 30 mg/kg/day in drinking water). These relaxations were inhibited by the selective AT2R blocker PD123319, N(G)-nitro-L-arginine methyl ester (L-NAME), and B2receptor antagonist HOE-140. Accordingly, nitric oxide (NO) production was increased by Ang II only in the aortas of treated SHR. After AT1R blockade, AT2R mRNA was significantly increased. These findings demonstrate that, in hypertensive rats, chronic AT1R blockade is associated with an inverted vasomotor response to Ang II via AT2R-mediated NO production.

CONCLUSIONS

The losartan-unmasked AT2R-vasorelaxation could significantly contribute to the beneficial hemodynamic effects of AT1R blockade. In view of this, our study highlights the importance of the integrated Ang II receptor network, which may help to define further the mechanisms of the well-established vascular protective effects of AT1R blockers.

Authors+Show Affiliations

Division of Cardiology, 2nd Faculty of Medicine, University La Sapienza, Rome, Italy.No affiliation info availableNo 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

15831358

Citation

Cosentino, Francesco, et al. "Angiotensin II Type 2 Receptors Contribute to Vascular Responses in Spontaneously Hypertensive Rats Treated With Angiotensin II Type 1 Receptor Antagonists." American Journal of Hypertension, vol. 18, no. 4 Pt 1, 2005, pp. 493-9.
Cosentino F, Savoia C, De Paolis P, et al. Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists. Am J Hypertens. 2005;18(4 Pt 1):493-9.
Cosentino, F., Savoia, C., De Paolis, P., Francia, P., Russo, A., Maffei, A., Venturelli, V., Schiavoni, M., Lembo, G., & Volpe, M. (2005). Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists. American Journal of Hypertension, 18(4 Pt 1), 493-9.
Cosentino F, et al. Angiotensin II Type 2 Receptors Contribute to Vascular Responses in Spontaneously Hypertensive Rats Treated With Angiotensin II Type 1 Receptor Antagonists. Am J Hypertens. 2005;18(4 Pt 1):493-9. PubMed PMID: 15831358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists. AU - Cosentino,Francesco, AU - Savoia,Carmine, AU - De Paolis,Paola, AU - Francia,Pietro, AU - Russo,Alessandro, AU - Maffei,Angelo, AU - Venturelli,Vanessa, AU - Schiavoni,Marzia, AU - Lembo,Giuseppe, AU - Volpe,Massimo, PY - 2004/07/22/received PY - 2004/09/20/revised PY - 2004/11/01/accepted PY - 2005/4/16/pubmed PY - 2005/7/6/medline PY - 2005/4/16/entrez SP - 493 EP - 9 JF - American journal of hypertension JO - Am. J. Hypertens. VL - 18 IS - 4 Pt 1 N2 - BACKGROUND: Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by Ang II type 1 (AT1) receptors. The effects of Ang II via the Ang II type 2 (AT2) receptor subtype (AT2R) are less well defined. Growing evidence shows the existence of cross-talk between the Ang II receptor subtypes, which is revealed by AT1R blockade. Hence, under certain conditions, AT2R may act as an antagonistic system with respect to the AT1R. METHODS: The present study was designed to investigate the effects of long-term treatment with the AT1R antagonist losartan on the AT2R-mediated response to Ang II in thoracic aortas isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Untreated animals from both groups were used as controls. The mRNA expression of AT1R and AT2R was measured by reverse transcription-polymerase chain reaction. RESULTS: During contraction in response to norepinephrine, Ang II induced concentration-dependent relaxation only in aortas isolated from SHR chronically treated with losartan (8 weeks; 30 mg/kg/day in drinking water). These relaxations were inhibited by the selective AT2R blocker PD123319, N(G)-nitro-L-arginine methyl ester (L-NAME), and B2receptor antagonist HOE-140. Accordingly, nitric oxide (NO) production was increased by Ang II only in the aortas of treated SHR. After AT1R blockade, AT2R mRNA was significantly increased. These findings demonstrate that, in hypertensive rats, chronic AT1R blockade is associated with an inverted vasomotor response to Ang II via AT2R-mediated NO production. CONCLUSIONS: The losartan-unmasked AT2R-vasorelaxation could significantly contribute to the beneficial hemodynamic effects of AT1R blockade. In view of this, our study highlights the importance of the integrated Ang II receptor network, which may help to define further the mechanisms of the well-established vascular protective effects of AT1R blockers. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/15831358/Angiotensin_II_type_2_receptors_contribute_to_vascular_responses_in_spontaneously_hypertensive_rats_treated_with_angiotensin_II_type_1_receptor_antagonists_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1016/j.amjhyper.2004.11.007 DB - PRIME DP - Unbound Medicine ER -