Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.

Chronic treatment with angiotensin receptor blockers is largely accepted for protecting cerebral circulation during hypertension, but beneficial effects of short-term treatments are questionable, as highlighted by the recent SCAST trial. We compared the impact of 10 days treatment with candesartan (...

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Autores principales:	Sébastien Foulquier, François Dupuis, Caroline Perrin-Sarrado, Katy Maguin Gatè, Pierre Leroy, Patrick Liminana, Jeffrey Atkinson, Christine Capdeville-Atkinson, Isabelle Lartaud
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4ddbc123bd6403281e382e222dc279f
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spelling	oai:doaj.org-article:d4ddbc123bd6403281e382e222dc279f2021-11-18T07:06:37ZDifferential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.1932-620310.1371/journal.pone.0042469https://doaj.org/article/d4ddbc123bd6403281e382e222dc279f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22957022/?tool=EBIhttps://doaj.org/toc/1932-6203Chronic treatment with angiotensin receptor blockers is largely accepted for protecting cerebral circulation during hypertension, but beneficial effects of short-term treatments are questionable, as highlighted by the recent SCAST trial. We compared the impact of 10 days treatment with candesartan (as SCAST) versus telmisartan (previously described to reverse arteriolar remodeling, chronic treatment) on pial arterioles of spontaneously hypertensive rats (SHR). We explored whether PPAR-gamma agonist activity or AT(1) receptor blockade are involved in their differential effects. In the first study, 4-month-old male SHR were treated with telmisartan (TELMI, 2 mg/kg per day) or candesartan cilexetil (CANDE, 10 mg/kg per day) and compared to vehicle treated SHR and normotensive WKY. In a second study, SHR were treated with CANDE, pioglitazone (a PPAR-gamma agonist, PIO 2.5 mg/kg per day) or CANDE+PIO, compared to TELMI. Internal diameter of pial arterioles (ID, cranial window) was measured at baseline, during hemorrhage-induced hypotension, or following suffusion of Ang II (10(-6) mol/L) or EDTA inactivation of smooth muscle cells (passive ID). PPAR-gamma and eNOS (target gene of PPAR-gamma) mRNA were evaluated in brain microvessels. For similar antihypertensive effects, TELMI (+44% versus SHR), but not CANDE, increased baseline ID. During hemorrhage, ID in TELMI group was similar to WKY, while ID in SHR and CANDE remained lower. In the second study, TELMI (+36%, versus SHR) and CANDE+PIO (+43%) increased baseline ID, but not CANDE or PIO alone. TELMI (-66%) and CANDE+PIO (-69%), but neither CANDE nor PIO alone, decreased Ang II-induced vasoconstriction. CANDE+PIO, but not CANDE, increased passive ID. In both studies, PPAR-gamma and eNOS expressions were higher in TELMI than CANDE. Short-term treatment with TELMI, but not with CANDE, reverses narrowing of pial arteriolar ID in SHR. This may involve PPAR-gamma related mechanisms, since CANDE+PIO treatment induced similar effects, and a better blockade of AT(1) receptors.Sébastien FoulquierFrançois DupuisCaroline Perrin-SarradoKaty Maguin GatèPierre LeroyPatrick LiminanaJeffrey AtkinsonChristine Capdeville-AtkinsonIsabelle LartaudPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e42469 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sébastien Foulquier François Dupuis Caroline Perrin-Sarrado Katy Maguin Gatè Pierre Leroy Patrick Liminana Jeffrey Atkinson Christine Capdeville-Atkinson Isabelle Lartaud Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.
description	Chronic treatment with angiotensin receptor blockers is largely accepted for protecting cerebral circulation during hypertension, but beneficial effects of short-term treatments are questionable, as highlighted by the recent SCAST trial. We compared the impact of 10 days treatment with candesartan (as SCAST) versus telmisartan (previously described to reverse arteriolar remodeling, chronic treatment) on pial arterioles of spontaneously hypertensive rats (SHR). We explored whether PPAR-gamma agonist activity or AT(1) receptor blockade are involved in their differential effects. In the first study, 4-month-old male SHR were treated with telmisartan (TELMI, 2 mg/kg per day) or candesartan cilexetil (CANDE, 10 mg/kg per day) and compared to vehicle treated SHR and normotensive WKY. In a second study, SHR were treated with CANDE, pioglitazone (a PPAR-gamma agonist, PIO 2.5 mg/kg per day) or CANDE+PIO, compared to TELMI. Internal diameter of pial arterioles (ID, cranial window) was measured at baseline, during hemorrhage-induced hypotension, or following suffusion of Ang II (10(-6) mol/L) or EDTA inactivation of smooth muscle cells (passive ID). PPAR-gamma and eNOS (target gene of PPAR-gamma) mRNA were evaluated in brain microvessels. For similar antihypertensive effects, TELMI (+44% versus SHR), but not CANDE, increased baseline ID. During hemorrhage, ID in TELMI group was similar to WKY, while ID in SHR and CANDE remained lower. In the second study, TELMI (+36%, versus SHR) and CANDE+PIO (+43%) increased baseline ID, but not CANDE or PIO alone. TELMI (-66%) and CANDE+PIO (-69%), but neither CANDE nor PIO alone, decreased Ang II-induced vasoconstriction. CANDE+PIO, but not CANDE, increased passive ID. In both studies, PPAR-gamma and eNOS expressions were higher in TELMI than CANDE. Short-term treatment with TELMI, but not with CANDE, reverses narrowing of pial arteriolar ID in SHR. This may involve PPAR-gamma related mechanisms, since CANDE+PIO treatment induced similar effects, and a better blockade of AT(1) receptors.
format	article
author	Sébastien Foulquier François Dupuis Caroline Perrin-Sarrado Katy Maguin Gatè Pierre Leroy Patrick Liminana Jeffrey Atkinson Christine Capdeville-Atkinson Isabelle Lartaud
author_facet	Sébastien Foulquier François Dupuis Caroline Perrin-Sarrado Katy Maguin Gatè Pierre Leroy Patrick Liminana Jeffrey Atkinson Christine Capdeville-Atkinson Isabelle Lartaud
author_sort	Sébastien Foulquier
title	Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.
title_short	Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.
title_full	Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.
title_fullStr	Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.
title_full_unstemmed	Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.
title_sort	differential effects of short-term treatment with two at1 receptor blockers on diameter of pial arterioles in shr.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d4ddbc123bd6403281e382e222dc279f
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Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR.

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