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Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR.
J Cardiovasc Pharmacol. 1997 Jul; 30(1):75-83.JC

Abstract

The structure and function of small arteries of different vascular beds in spontaneously hypertensive rats (SHRs) are altered relative to Wistar-Kyoto (WKY) control rats, and these differences may be blunted under treatment with angiotensin-converting enzyme inhibitors. To determine whether this effect of angiotensin-converting enzyme inhibitors was caused by the interruption of the renin-angiotensin system, our experiments were conducted with an AT1 angiotensin-receptor antagonist to evaluate its ability to induce regression of hypertrophy of resistance arteries in SHRs. The result of treatment of SHRs with losartan, an orally active selective angiotensin AT1 receptor antagonist was examined at a low (20 mg/kg/day) and a high (60 mg/kg/day) oral dose in SHRs once blood pressure had been elevated for some time. SHRs were treated for 12 weeks with losartan. Blood pressure was significantly reduced by losartan treatment from 210 +/- 2 mm Hg in untreated SHRs to 181 +/- 1 mm Hg (low dose) and 156 +/- 4 mm Hg (high dose) (p < 0.01). Cardiac and aortic hypertrophy were dose-dependently reduced in treated SHRs. Coronary, renal, mesenteric, and femoral small arteries (luminal diameter, 200-250 microm) studied on an isometric wire myograph and pressurized mesenteric small arteries examined under isobaric conditions exhibited significant hypertrophy and inward remodeling in SHRs in comparison to WKY rats. Losartan treatment resulted in a dose-dependent reduction in the media thickness and mediato-lumen ratio in small arteries from the four vascular beds studied on the wire myograph and in pressurized mesenteric small arteries. Endothelium-dependent relaxation studied in pressurized arteries was enhanced, and acetylcholine-induced endothelium-dependent contractions studied on the wire myograph were abolished in losartan-treated SHRs relative to untreated SHRs. In WKY rats, treatment had no effect. These results demonstrate that treatment with the selective angiotensin II receptor antagonist losartan, even at doses that reduce blood pressure only moderately, induces regression of cardiovascular hypertrophy and of endothelial dysfunction in genetic hypertension in the rat.

Authors+Show Affiliations

MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9268224

Citation

Li, J S., et al. "Effect of AT1 Angiotensin-receptor Blockade On Structure and Function of Small Arteries in SHR." Journal of Cardiovascular Pharmacology, vol. 30, no. 1, 1997, pp. 75-83.
Li JS, Sharifi AM, Schiffrin EL. Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR. J Cardiovasc Pharmacol. 1997;30(1):75-83.
Li, J. S., Sharifi, A. M., & Schiffrin, E. L. (1997). Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR. Journal of Cardiovascular Pharmacology, 30(1), 75-83.
Li JS, Sharifi AM, Schiffrin EL. Effect of AT1 Angiotensin-receptor Blockade On Structure and Function of Small Arteries in SHR. J Cardiovasc Pharmacol. 1997;30(1):75-83. PubMed PMID: 9268224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR. AU - Li,J S, AU - Sharifi,A M, AU - Schiffrin,E L, PY - 1997/7/1/pubmed PY - 1997/7/1/medline PY - 1997/7/1/entrez SP - 75 EP - 83 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 30 IS - 1 N2 - The structure and function of small arteries of different vascular beds in spontaneously hypertensive rats (SHRs) are altered relative to Wistar-Kyoto (WKY) control rats, and these differences may be blunted under treatment with angiotensin-converting enzyme inhibitors. To determine whether this effect of angiotensin-converting enzyme inhibitors was caused by the interruption of the renin-angiotensin system, our experiments were conducted with an AT1 angiotensin-receptor antagonist to evaluate its ability to induce regression of hypertrophy of resistance arteries in SHRs. The result of treatment of SHRs with losartan, an orally active selective angiotensin AT1 receptor antagonist was examined at a low (20 mg/kg/day) and a high (60 mg/kg/day) oral dose in SHRs once blood pressure had been elevated for some time. SHRs were treated for 12 weeks with losartan. Blood pressure was significantly reduced by losartan treatment from 210 +/- 2 mm Hg in untreated SHRs to 181 +/- 1 mm Hg (low dose) and 156 +/- 4 mm Hg (high dose) (p < 0.01). Cardiac and aortic hypertrophy were dose-dependently reduced in treated SHRs. Coronary, renal, mesenteric, and femoral small arteries (luminal diameter, 200-250 microm) studied on an isometric wire myograph and pressurized mesenteric small arteries examined under isobaric conditions exhibited significant hypertrophy and inward remodeling in SHRs in comparison to WKY rats. Losartan treatment resulted in a dose-dependent reduction in the media thickness and mediato-lumen ratio in small arteries from the four vascular beds studied on the wire myograph and in pressurized mesenteric small arteries. Endothelium-dependent relaxation studied in pressurized arteries was enhanced, and acetylcholine-induced endothelium-dependent contractions studied on the wire myograph were abolished in losartan-treated SHRs relative to untreated SHRs. In WKY rats, treatment had no effect. These results demonstrate that treatment with the selective angiotensin II receptor antagonist losartan, even at doses that reduce blood pressure only moderately, induces regression of cardiovascular hypertrophy and of endothelial dysfunction in genetic hypertension in the rat. SN - 0160-2446 UR - https://www.unboundmedicine.com/medline/citation/9268224/Effect_of_AT1_angiotensin_receptor_blockade_on_structure_and_function_of_small_arteries_in_SHR_ L2 - https://doi.org/10.1097/00005344-199707000-00011 DB - PRIME DP - Unbound Medicine ER -